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data-event-name="pinnable-header.vector-toc.pin">move to sidebar</button> <button class="vector-pinnable-header-toggle-button vector-pinnable-header-unpin-button" data-event-name="pinnable-header.vector-toc.unpin">hide</button> </div> <ul class="vector-toc-contents" id="mw-panel-toc-list"> <li id="toc-mw-content-text" class="vector-toc-list-item vector-toc-level-1"> <a href="#" class="vector-toc-link"> <div class="vector-toc-text">(Top)</div> </a> </li> <li id="toc-Nomenclature" class="vector-toc-list-item vector-toc-level-1"> <a class="vector-toc-link" href="#Nomenclature"> <div class="vector-toc-text"> <span class="vector-toc-numb">1</span> <span>Nomenclature</span> </div> </a> <ul id="toc-Nomenclature-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Classification" class="vector-toc-list-item vector-toc-level-1"> <a class="vector-toc-link" href="#Classification"> <div class="vector-toc-text"> <span class="vector-toc-numb">2</span> <span>Classification</span> </div> </a> <button aria-controls="toc-Classification-sublist" class="cdx-button cdx-button--weight-quiet cdx-button--icon-only vector-toc-toggle"> <span class="vector-icon mw-ui-icon-wikimedia-expand"></span> <span>Toggle Classification subsection</span> </button> <ul id="toc-Classification-sublist" class="vector-toc-list"> <li id="toc-Non-depolarizing_blocking_agents" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Non-depolarizing_blocking_agents"> <div class="vector-toc-text"> <span class="vector-toc-numb">2.1</span> <span>Non-depolarizing blocking agents</span> </div> </a> <ul id="toc-Non-depolarizing_blocking_agents-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Depolarizing_blocking_agents" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Depolarizing_blocking_agents"> <div class="vector-toc-text"> <span class="vector-toc-numb">2.2</span> <span>Depolarizing blocking agents</span> </div> </a> <ul id="toc-Depolarizing_blocking_agents-sublist" class="vector-toc-list"> <li id="toc-Dosing/onset_of_action" class="vector-toc-list-item vector-toc-level-3"> <a class="vector-toc-link" href="#Dosing/onset_of_action"> <div class="vector-toc-text"> <span class="vector-toc-numb">2.2.1</span> <span>Dosing/onset of action</span> </div> </a> <ul id="toc-Dosing/onset_of_action-sublist" class="vector-toc-list"> </ul> </li> </ul> </li> <li id="toc-Comparison_of_drugs" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Comparison_of_drugs"> <div class="vector-toc-text"> <span class="vector-toc-numb">2.3</span> <span>Comparison of drugs</span> </div> </a> <ul id="toc-Comparison_of_drugs-sublist" class="vector-toc-list"> </ul> </li> </ul> </li> <li id="toc-Physiology_at_the_Neuromuscular_Junction" class="vector-toc-list-item vector-toc-level-1"> <a class="vector-toc-link" href="#Physiology_at_the_Neuromuscular_Junction"> <div class="vector-toc-text"> <span class="vector-toc-numb">3</span> <span>Physiology at the Neuromuscular Junction</span> </div> </a> <ul id="toc-Physiology_at_the_Neuromuscular_Junction-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Mechanism_of_action" class="vector-toc-list-item vector-toc-level-1"> <a class="vector-toc-link" href="#Mechanism_of_action"> <div class="vector-toc-text"> <span class="vector-toc-numb">4</span> <span>Mechanism of action</span> </div> </a> <ul id="toc-Mechanism_of_action-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Structural_and_conformational_action_relationship" class="vector-toc-list-item vector-toc-level-1"> <a class="vector-toc-link" href="#Structural_and_conformational_action_relationship"> <div class="vector-toc-text"> <span class="vector-toc-numb">5</span> <span>Structural and conformational action relationship</span> </div> </a> <button aria-controls="toc-Structural_and_conformational_action_relationship-sublist" class="cdx-button cdx-button--weight-quiet cdx-button--icon-only vector-toc-toggle"> <span class="vector-icon mw-ui-icon-wikimedia-expand"></span> <span>Toggle Structural and conformational action relationship subsection</span> </button> <ul id="toc-Structural_and_conformational_action_relationship-sublist" class="vector-toc-list"> <li id="toc-Molecular_length_and_rigidity" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Molecular_length_and_rigidity"> <div class="vector-toc-text"> <span class="vector-toc-numb">5.1</span> <span>Molecular length and rigidity</span> </div> </a> <ul id="toc-Molecular_length_and_rigidity-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Beers_and_Reich's_law" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Beers_and_Reich's_law"> <div class="vector-toc-text"> <span class="vector-toc-numb">5.2</span> <span>Beers and Reich's law</span> </div> </a> <ul id="toc-Beers_and_Reich's_law-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Rational_design" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Rational_design"> <div class="vector-toc-text"> <span class="vector-toc-numb">5.3</span> <span>Rational design</span> </div> </a> <ul id="toc-Rational_design-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Potency" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Potency"> <div class="vector-toc-text"> <span class="vector-toc-numb">5.4</span> <span>Potency</span> </div> </a> <ul id="toc-Potency-sublist" class="vector-toc-list"> </ul> </li> </ul> </li> <li id="toc-Pharmacokinetics" class="vector-toc-list-item vector-toc-level-1"> <a class="vector-toc-link" href="#Pharmacokinetics"> <div class="vector-toc-text"> <span class="vector-toc-numb">6</span> <span>Pharmacokinetics</span> </div> </a> <ul id="toc-Pharmacokinetics-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Medical_Use" class="vector-toc-list-item vector-toc-level-1"> <a class="vector-toc-link" href="#Medical_Use"> <div class="vector-toc-text"> <span class="vector-toc-numb">7</span> <span>Medical Use</span> </div> </a> <button aria-controls="toc-Medical_Use-sublist" class="cdx-button cdx-button--weight-quiet cdx-button--icon-only vector-toc-toggle"> <span class="vector-icon mw-ui-icon-wikimedia-expand"></span> <span>Toggle Medical Use subsection</span> </button> <ul id="toc-Medical_Use-sublist" class="vector-toc-list"> <li id="toc-Endotracheal_intubation" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Endotracheal_intubation"> <div class="vector-toc-text"> <span class="vector-toc-numb">7.1</span> <span>Endotracheal intubation</span> </div> </a> <ul id="toc-Endotracheal_intubation-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Facilitation_of_surgery" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Facilitation_of_surgery"> <div class="vector-toc-text"> <span class="vector-toc-numb">7.2</span> <span>Facilitation of surgery</span> </div> </a> <ul id="toc-Facilitation_of_surgery-sublist" class="vector-toc-list"> </ul> </li> </ul> </li> <li id="toc-Adverse_effects" class="vector-toc-list-item vector-toc-level-1"> <a class="vector-toc-link" href="#Adverse_effects"> <div class="vector-toc-text"> <span class="vector-toc-numb">8</span> <span>Adverse effects</span> </div> </a> <ul id="toc-Adverse_effects-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Interactions" class="vector-toc-list-item vector-toc-level-1"> <a class="vector-toc-link" href="#Interactions"> <div class="vector-toc-text"> <span class="vector-toc-numb">9</span> <span>Interactions</span> </div> </a> <button aria-controls="toc-Interactions-sublist" class="cdx-button cdx-button--weight-quiet cdx-button--icon-only vector-toc-toggle"> <span class="vector-icon mw-ui-icon-wikimedia-expand"></span> <span>Toggle Interactions subsection</span> </button> <ul id="toc-Interactions-sublist" class="vector-toc-list"> <li id="toc-Combination_of_NMBAs" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Combination_of_NMBAs"> <div class="vector-toc-text"> <span class="vector-toc-numb">9.1</span> <span>Combination of NMBAs</span> </div> </a> <ul id="toc-Combination_of_NMBAs-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Inhaled_anesthetics" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Inhaled_anesthetics"> <div class="vector-toc-text"> <span class="vector-toc-numb">9.2</span> <span>Inhaled anesthetics</span> </div> </a> <ul id="toc-Inhaled_anesthetics-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Antibiotics" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Antibiotics"> <div class="vector-toc-text"> <span class="vector-toc-numb">9.3</span> <span>Antibiotics</span> </div> </a> <ul id="toc-Antibiotics-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Anti-seizure_drugs" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Anti-seizure_drugs"> <div class="vector-toc-text"> <span class="vector-toc-numb">9.4</span> <span>Anti-seizure drugs</span> </div> </a> <ul id="toc-Anti-seizure_drugs-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Lithium" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Lithium"> <div class="vector-toc-text"> <span class="vector-toc-numb">9.5</span> <span>Lithium</span> </div> </a> <ul id="toc-Lithium-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Antidepressants" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Antidepressants"> <div class="vector-toc-text"> <span class="vector-toc-numb">9.6</span> <span>Antidepressants</span> </div> </a> <ul id="toc-Antidepressants-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Local_anesthetics_(LAs)" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Local_anesthetics_(LAs)"> <div class="vector-toc-text"> <span class="vector-toc-numb">9.7</span> <span>Local anesthetics (LAs)</span> </div> </a> <ul id="toc-Local_anesthetics_(LAs)-sublist" class="vector-toc-list"> </ul> </li> </ul> </li> <li id="toc-Estimating_effect" class="vector-toc-list-item vector-toc-level-1"> <a class="vector-toc-link" href="#Estimating_effect"> <div class="vector-toc-text"> <span class="vector-toc-numb">10</span> <span>Estimating effect</span> </div> </a> <ul id="toc-Estimating_effect-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Reversal" class="vector-toc-list-item vector-toc-level-1"> <a class="vector-toc-link" href="#Reversal"> <div class="vector-toc-text"> <span class="vector-toc-numb">11</span> <span>Reversal</span> </div> </a> <ul id="toc-Reversal-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-History" class="vector-toc-list-item vector-toc-level-1"> <a class="vector-toc-link" href="#History"> <div class="vector-toc-text"> <span class="vector-toc-numb">12</span> <span>History</span> </div> </a> <button aria-controls="toc-History-sublist" class="cdx-button cdx-button--weight-quiet cdx-button--icon-only vector-toc-toggle"> <span class="vector-icon mw-ui-icon-wikimedia-expand"></span> <span>Toggle History subsection</span> </button> <ul id="toc-History-sublist" class="vector-toc-list"> <li id="toc-Outdated_treatment" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Outdated_treatment"> <div class="vector-toc-text"> <span class="vector-toc-numb">12.1</span> <span>Outdated treatment</span> </div> </a> <ul id="toc-Outdated_treatment-sublist" class="vector-toc-list"> </ul> </li> </ul> </li> <li id="toc-See_also" class="vector-toc-list-item vector-toc-level-1"> <a class="vector-toc-link" href="#See_also"> <div class="vector-toc-text"> <span class="vector-toc-numb">13</span> <span>See also</span> </div> </a> <ul id="toc-See_also-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-References" class="vector-toc-list-item vector-toc-level-1"> <a class="vector-toc-link" href="#References"> <div class="vector-toc-text"> <span class="vector-toc-numb">14</span> <span>References</span> </div> </a> <ul id="toc-References-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-External_links" class="vector-toc-list-item vector-toc-level-1"> <a class="vector-toc-link" href="#External_links"> <div class="vector-toc-text"> <span class="vector-toc-numb">15</span> <span>External links</span> </div> </a> <ul id="toc-External_links-sublist" class="vector-toc-list"> </ul> </li> </ul> </div> </div> </nav> </div> </div> <div class="mw-content-container"> <main id="content" class="mw-body"> <header class="mw-body-header vector-page-titlebar"> <nav aria-label="Contents" class="vector-toc-landmark"> <div id="vector-page-titlebar-toc" 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drug</span></h1> <div id="p-lang-btn" class="vector-dropdown mw-portlet mw-portlet-lang" > <input type="checkbox" id="p-lang-btn-checkbox" role="button" aria-haspopup="true" data-event-name="ui.dropdown-p-lang-btn" class="vector-dropdown-checkbox mw-interlanguage-selector" aria-label="Go to an article in another language. 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mw-list-item"><a href="https://ca.wikipedia.org/wiki/Blocador_neuromuscular" title="Blocador neuromuscular – Catalan" lang="ca" hreflang="ca" data-title="Blocador neuromuscular" data-language-autonym="Català" data-language-local-name="Catalan" class="interlanguage-link-target"><span>Català</span></a></li><li class="interlanguage-link interwiki-es mw-list-item"><a href="https://es.wikipedia.org/wiki/Bloqueador_neuromuscular" title="Bloqueador neuromuscular – Spanish" lang="es" hreflang="es" data-title="Bloqueador neuromuscular" data-language-autonym="Español" data-language-local-name="Spanish" class="interlanguage-link-target"><span>Español</span></a></li><li class="interlanguage-link interwiki-fa mw-list-item"><a href="https://fa.wikipedia.org/wiki/%D8%AF%D8%A7%D8%B1%D9%88%DB%8C_%D9%85%D8%B3%D8%AF%D9%88%D8%AF%DA%A9%D9%86%D9%86%D8%AF%D9%87_%D8%B9%D8%B5%D8%A8%DB%8C-%D8%B9%D8%B6%D9%84%D8%A7%D9%86%DB%8C" title="داروی مسدودکننده عصبی-عضلانی – Persian" lang="fa" hreflang="fa" data-title="داروی مسدودکننده عصبی-عضلانی" data-language-autonym="فارسی" data-language-local-name="Persian" class="interlanguage-link-target"><span>فارسی</span></a></li><li class="interlanguage-link interwiki-it mw-list-item"><a href="https://it.wikipedia.org/wiki/Bloccante_neuromuscolare" title="Bloccante neuromuscolare – Italian" lang="it" hreflang="it" data-title="Bloccante neuromuscolare" data-language-autonym="Italiano" data-language-local-name="Italian" class="interlanguage-link-target"><span>Italiano</span></a></li><li class="interlanguage-link interwiki-ja mw-list-item"><a href="https://ja.wikipedia.org/wiki/%E7%A5%9E%E7%B5%8C%E7%AD%8B%E9%81%AE%E6%96%AD%E8%96%AC" title="神経筋遮断薬 – Japanese" lang="ja" hreflang="ja" data-title="神経筋遮断薬" data-language-autonym="日本語" data-language-local-name="Japanese" class="interlanguage-link-target"><span>日本語</span></a></li><li class="interlanguage-link interwiki-pl mw-list-item"><a href="https://pl.wikipedia.org/wiki/Depolaryzuj%C4%85ce_%C5%9Brodki_zwiotczaj%C4%85ce" title="Depolaryzujące środki zwiotczające – Polish" lang="pl" hreflang="pl" data-title="Depolaryzujące środki zwiotczające" data-language-autonym="Polski" data-language-local-name="Polish" class="interlanguage-link-target"><span>Polski</span></a></li><li class="interlanguage-link interwiki-pt mw-list-item"><a href="https://pt.wikipedia.org/wiki/Bloqueador_neuromuscular" title="Bloqueador neuromuscular – Portuguese" lang="pt" hreflang="pt" data-title="Bloqueador neuromuscular" data-language-autonym="Português" data-language-local-name="Portuguese" class="interlanguage-link-target"><span>Português</span></a></li><li class="interlanguage-link interwiki-zh mw-list-item"><a href="https://zh.wikipedia.org/wiki/%E7%A5%9E%E7%BB%8F%E8%82%8C%E8%82%89%E9%98%BB%E6%BB%9E%E8%8D%AF" title="神经肌肉阻滞药 – Chinese" lang="zh" hreflang="zh" data-title="神经肌肉阻滞药" data-language-autonym="中文" data-language-local-name="Chinese" 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<div class="mw-indicators"> </div> <div id="siteSub" class="noprint">From Wikipedia, the free encyclopedia</div> </div> <div id="contentSub"><div id="mw-content-subtitle"></div></div> <div id="mw-content-text" class="mw-body-content"><div class="mw-content-ltr mw-parser-output" lang="en" dir="ltr"><div class="shortdescription nomobile noexcerpt noprint searchaux" style="display:none">Type of paralyzing anesthetic including lepto- and pachycurares</div> <p class="mw-empty-elt"> </p> <figure class="mw-default-size" typeof="mw:File/Thumb"><a href="/wiki/File:Synapse_diag3.png" class="mw-file-description"><img src="//upload.wikimedia.org/wikipedia/commons/thumb/c/ca/Synapse_diag3.png/220px-Synapse_diag3.png" decoding="async" width="220" height="203" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/c/ca/Synapse_diag3.png/330px-Synapse_diag3.png 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/c/ca/Synapse_diag3.png/440px-Synapse_diag3.png 2x" data-file-width="532" data-file-height="491" /></a><figcaption>Global view of a neuromuscular junction: <div><ol><li><a href="/wiki/Axon" title="Axon">Axon</a></li><li>Motor end-plate</li><li><a href="/wiki/Skeletal_muscle#Skeletal_muscle_cells" title="Skeletal muscle">Muscle fiber</a></li><li><a href="/wiki/Myofibril" title="Myofibril">Myofibril</a></li></ol></div></figcaption></figure> <figure class="mw-default-size" typeof="mw:File/Thumb"><a href="/wiki/File:Synapse_diag4.png" class="mw-file-description"><img src="//upload.wikimedia.org/wikipedia/commons/thumb/2/2b/Synapse_diag4.png/220px-Synapse_diag4.png" decoding="async" width="220" height="200" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/2/2b/Synapse_diag4.png/330px-Synapse_diag4.png 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/2/2b/Synapse_diag4.png/440px-Synapse_diag4.png 2x" data-file-width="627" data-file-height="571" /></a><figcaption>Detailed view of a neuromuscular junction: <div><ol><li><a href="/wiki/Presynaptic" class="mw-redirect" title="Presynaptic">Presynaptic</a> terminal</li><li><a href="/wiki/Sarcolemma" title="Sarcolemma">Sarcolemma</a></li><li><a href="/wiki/Synaptic_vesicle" title="Synaptic vesicle">Synaptic vesicle</a></li><li><a href="/wiki/Nicotinic_acetylcholine_receptor" title="Nicotinic acetylcholine receptor">Nicotinic acetylcholine receptor</a></li><li><a href="/wiki/Mitochondrion" title="Mitochondrion">Mitochondrion</a></li></ol></div></figcaption></figure> <style data-mw-deduplicate="TemplateStyles:r1236090951">.mw-parser-output .hatnote{font-style:italic}.mw-parser-output div.hatnote{padding-left:1.6em;margin-bottom:0.5em}.mw-parser-output .hatnote i{font-style:normal}.mw-parser-output .hatnote+link+.hatnote{margin-top:-0.5em}@media print{body.ns-0 .mw-parser-output .hatnote{display:none!important}}</style><div role="note" class="hatnote navigation-not-searchable">For similar term named Cholinesterase–blocking drug, see <a href="/wiki/Cholinesterase_inhibitor" title="Cholinesterase inhibitor">Cholinesterase inhibitor</a>.</div> <p><b>Neuromuscular-blocking drugs</b>, or <b>Neuromuscular blocking agents</b> (<b>NMBAs</b>), block transmission at the <a href="/wiki/Neuromuscular_junction" title="Neuromuscular junction">neuromuscular junction</a>,<sup id="cite_ref-urlDorlands_Medical_Dictionary:neuromuscular_blocking_agent_1-0" class="reference"><a href="#cite_note-urlDorlands_Medical_Dictionary:neuromuscular_blocking_agent-1"><span class="cite-bracket">[</span>1<span class="cite-bracket">]</span></a></sup> causing <a href="/wiki/Paralysis" title="Paralysis">paralysis</a> of the affected <a href="/wiki/Skeletal_muscle" title="Skeletal muscle">skeletal muscles</a>. This is accomplished via their action on the post-synaptic acetylcholine (Nm) receptors. </p><p>In clinical use, neuromuscular block is used adjunctively to <a href="/wiki/Anesthesia" title="Anesthesia">anesthesia</a> to produce <a href="/wiki/Paralysis" title="Paralysis">paralysis</a>, firstly to paralyze the vocal cords, and permit <a href="/wiki/Endotracheal_intubation" class="mw-redirect" title="Endotracheal intubation">endotracheal intubation</a>,<sup id="cite_ref-2" class="reference"><a href="#cite_note-2"><span class="cite-bracket">[</span>2<span class="cite-bracket">]</span></a></sup> and secondly to optimize the surgical field by inhibiting spontaneous ventilation, and causing relaxation of skeletal muscles. Because the appropriate dose of neuromuscular-blocking drug may paralyze muscles required for breathing (i.e., the diaphragm), <a href="/wiki/Mechanical_ventilation" title="Mechanical ventilation">mechanical ventilation</a> should be available to maintain adequate <a href="/wiki/Respiration_(physiology)" title="Respiration (physiology)">respiration</a>. </p><p>This class of medications helps to reduce patient movement, breathing, or ventilator dyssynchrony and allows lower insufflation pressures during laparoscopy.<sup id="cite_ref-3" class="reference"><a href="#cite_note-3"><span class="cite-bracket">[</span>3<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-4" class="reference"><a href="#cite_note-4"><span class="cite-bracket">[</span>4<span class="cite-bracket">]</span></a></sup> It has several indications for use in the intense care unit. It can help reduce hoarseness in voice as well as injury to the vocal cord during intubation. In addition, it plays an important role in facilitating <a href="/wiki/Mechanical_ventilation" title="Mechanical ventilation">mechanical ventilation</a> in patients with poor lung function. </p><p>Patients are still aware of pain even after full <a href="/wiki/Conduction_block" class="mw-redirect" title="Conduction block">conduction block</a> has occurred; hence, <a href="/wiki/General_anesthetic" class="mw-redirect" title="General anesthetic">general anesthetics</a> and/or <a href="/wiki/Analgesic" title="Analgesic">analgesics</a> must also be given to prevent <a href="/wiki/Anesthesia_awareness" title="Anesthesia awareness">anesthesia awareness</a>. </p> <meta property="mw:PageProp/toc" /> <div class="mw-heading mw-heading2"><h2 id="Nomenclature">Nomenclature</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Neuromuscular-blocking_drug&action=edit&section=1" title="Edit section: Nomenclature"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>Neuromuscular blocking drugs are often classified into two broad classes: </p> <ul><li>Pachycurares, which are bulky molecules with nondepolarizing activity</li> <li>Leptocurares, which are thin and flexible molecules that tend to have depolarizing activity.<sup id="cite_ref-Bowman_2006_5-0" class="reference"><a href="#cite_note-Bowman_2006-5"><span class="cite-bracket">[</span>5<span class="cite-bracket">]</span></a></sup></li></ul> <p>It is also common to classify them based on their chemical structure. </p> <ul><li><b>Acetylcholine, suxamethonium, and decamethonium</b></li></ul> <p><a href="/wiki/Suxamethonium" class="mw-redirect" title="Suxamethonium">Suxamethonium</a> was synthesised by connecting two <a href="/wiki/Acetylcholine" title="Acetylcholine">acetylcholine</a> <a href="/wiki/Molecules" class="mw-redirect" title="Molecules">molecules</a> and has the same number of heavy <a href="/wiki/Atoms" class="mw-redirect" title="Atoms">atoms</a> between methonium heads as <a href="/wiki/Decamethonium" title="Decamethonium">decamethonium</a>. Just like acetylcholine, succinylcholine, decamethonium and other <a href="/wiki/Polymethylene" class="mw-redirect" title="Polymethylene">polymethylene</a> chains, of the appropriate length and with two methonium, heads have small <a href="/wiki/Methyl" class="mw-redirect" title="Methyl">trimethyl</a> <a href="/wiki/Quaternary_ammonium" class="mw-redirect" title="Quaternary ammonium">onium</a> heads and flexible links. They all exhibit a depolarizing block. </p> <ul><li><b>Aminosteroids</b></li></ul> <link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1236090951"><div role="note" class="hatnote navigation-not-searchable">Main article: <a href="/wiki/Aminosteroid" title="Aminosteroid">Aminosteroid</a></div> <p><a href="/wiki/Pancuronium" class="mw-redirect" title="Pancuronium">Pancuronium</a>, <a href="/wiki/Vecuronium" class="mw-redirect" title="Vecuronium">vecuronium</a>, <a href="/wiki/Rocuronium" class="mw-redirect" title="Rocuronium">rocuronium</a>, <a href="/wiki/Rapacuronium" class="mw-redirect" title="Rapacuronium">rapacuronium</a>, <a href="/wiki/Dacuronium" class="mw-redirect" title="Dacuronium">dacuronium</a>, <a href="/wiki/Malou%C3%A8tine" class="mw-redirect" title="Malouètine">malouètine</a>, <a href="/wiki/Dihydrochandonium" title="Dihydrochandonium">dihydrochandonium</a>, <a href="/wiki/Dipyrandium" title="Dipyrandium">dipyrandium</a>, <a href="/wiki/Pipecuronium" class="mw-redirect" title="Pipecuronium">pipecuronium</a>, <a href="/wiki/Chandonium" class="mw-redirect" title="Chandonium">chandonium</a> (HS-310), <a href="/w/index.php?title=HS-342&action=edit&redlink=1" class="new" title="HS-342 (page does not exist)">HS-342</a> and other HS- compounds are aminosteroidal agents. They have in common the <a href="/wiki/Steroid" title="Steroid">steroid</a> structural base, which provides a rigid and bulky body. Most of the agents in this category would also be classified as non-depolarizing. </p> <ul><li><b>Tetrahydroisoquinoline derivatives</b></li></ul> <p>Compounds based on the <a href="/wiki/Tetrahydroisoquinoline" title="Tetrahydroisoquinoline">tetrahydroisoquinoline</a> moiety such as <a href="/wiki/Atracurium" class="mw-redirect" title="Atracurium">atracurium</a>, <a href="/wiki/Mivacurium" class="mw-redirect" title="Mivacurium">mivacurium</a>, and <a href="/wiki/Doxacurium" class="mw-redirect" title="Doxacurium">doxacurium</a> would fall in this category. They have a long and flexible chain between the <a href="/wiki/Quaternary_ammonium" class="mw-redirect" title="Quaternary ammonium">onium</a> heads, except for the double bond of <a href="/wiki/Mivacurium" class="mw-redirect" title="Mivacurium">mivacurium</a>. <a href="/wiki/Tubocurarine" class="mw-redirect" title="Tubocurarine">D-tubocurarine</a> and <a href="/wiki/Dimethyltubocurarine" class="mw-redirect" title="Dimethyltubocurarine">dimethyltubocurarine</a> are also in this category. Most of the agents in this category would be classified as non-depolarizing. </p> <ul><li><b>Gallamine and other chemical classes</b></li></ul> <p><a href="/wiki/Gallamine" class="mw-redirect" title="Gallamine">Gallamine</a> is a trisquaternary ether with three ethonium heads attached to a <a href="/wiki/Phenyl" class="mw-redirect" title="Phenyl">phenyl</a> ring through an ether linkage. Many other different structures have been used for their muscle relaxant effect such as <a href="/wiki/Alcuronium" class="mw-redirect" title="Alcuronium">alcuronium</a> (alloferin), <a href="/w/index.php?title=Anatruxonium&action=edit&redlink=1" class="new" title="Anatruxonium (page does not exist)">anatruxonium</a>, <a href="/w/index.php?title=Diadonium&action=edit&redlink=1" class="new" title="Diadonium (page does not exist)">diadonium</a>, <a href="/wiki/Fazadinium" class="mw-redirect" title="Fazadinium">fazadinium</a> (AH8165) and <a href="/w/index.php?title=Tropeinium&action=edit&redlink=1" class="new" title="Tropeinium (page does not exist)">tropeinium</a>. </p> <ul><li><b>Novel NMB agents</b></li></ul> <p>In recent years much research has been devoted to new types of quaternary ammonium muscle relaxants. These are asymmetrical diester <a href="/w/index.php?title=Isoquinolinium&action=edit&redlink=1" class="new" title="Isoquinolinium (page does not exist)">isoquinolinium</a> compounds and bis-benzyltropinium compounds that are bistropinium salts of various <a href="/wiki/Acid" title="Acid">diacids</a>. These classes have been developed to create <a href="/wiki/Muscle_relaxants" class="mw-redirect" title="Muscle relaxants">muscle relaxants</a> that are faster and shorter acting. Both the asymmetric structure of diester isoquinolinium compounds and the acyloxylated benzyl groups on the bisbenzyltropiniums destabilizes them and can lead to spontaneous breakdown and therefore possibly a shorter duration of action.<sup id="cite_ref-Lee_2001_6-0" class="reference"><a href="#cite_note-Lee_2001-6"><span class="cite-bracket">[</span>6<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading2"><h2 id="Classification">Classification</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Neuromuscular-blocking_drug&action=edit&section=2" title="Edit section: Classification"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>These drugs fall into two groups: </p> <ul><li><b>Non-depolarizing blocking agents</b>: These agents constitute the majority of the clinically relevant neuromuscular blockers. They act by competitively blocking the binding of ACh to its receptors, and in some cases, they also directly block the <a href="/wiki/Ionotropic" class="mw-redirect" title="Ionotropic">ionotropic</a> activity of the ACh receptors.<sup id="cite_ref-pmid8866353_7-0" class="reference"><a href="#cite_note-pmid8866353-7"><span class="cite-bracket">[</span>7<span class="cite-bracket">]</span></a></sup></li> <li><b>Depolarizing blocking agents</b>: These agents act by <a href="/wiki/Depolarization" title="Depolarization">depolarizing</a> the <a href="/wiki/Sarcolemma" title="Sarcolemma">sarcolemma</a> of the skeletal <a href="/wiki/Muscle_fiber" class="mw-redirect" title="Muscle fiber">muscle fiber</a>. This persistent depolarization makes the muscle fiber resistant to further stimulation by ACh.</li></ul> <div class="mw-heading mw-heading3"><h3 id="Non-depolarizing_blocking_agents">Non-depolarizing blocking agents</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Neuromuscular-blocking_drug&action=edit&section=3" title="Edit section: Non-depolarizing blocking agents"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>A <b>neuromuscular non-depolarizing agent</b> is a form of <a href="/wiki/Neuromuscular_blocker" class="mw-redirect" title="Neuromuscular blocker">neuromuscular blocker</a> that does not depolarize the <a href="/wiki/Motor_end_plate" class="mw-redirect" title="Motor end plate">motor end plate</a>.<sup id="cite_ref-8" class="reference"><a href="#cite_note-8"><span class="cite-bracket">[</span>8<span class="cite-bracket">]</span></a></sup> </p><p>The quaternary ammonium muscle relaxants belong to this class. Quaternary ammonium muscle relaxants are <a href="/wiki/Quaternary_ammonium_salt" class="mw-redirect" title="Quaternary ammonium salt">quaternary ammonium salts</a> used as <a href="/wiki/Drugs" class="mw-redirect" title="Drugs">drugs</a> for <a href="/wiki/Muscle_relaxant" title="Muscle relaxant">muscle relaxation</a>, most commonly in <a href="/wiki/Anesthesia" title="Anesthesia">anesthesia</a>. It is necessary to prevent spontaneous movement of muscle during <a href="/wiki/Surgery" title="Surgery">surgical operations</a>. Muscle relaxants inhibit <a href="/wiki/Neuron" title="Neuron">neuron</a> transmission to muscle by blocking the <a href="/wiki/Nicotinic_acetylcholine_receptor" title="Nicotinic acetylcholine receptor">nicotinic acetylcholine receptor</a>. What they have in common, and is necessary for their effect, is the structural presence of quaternary ammonium groups, usually two. Some of them are found in nature and others are <a href="/wiki/Chemical_synthesis" title="Chemical synthesis">synthesized</a> molecules.<sup id="cite_ref-T._Raghavendra_2002_9-0" class="reference"><a href="#cite_note-T._Raghavendra_2002-9"><span class="cite-bracket">[</span>9<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-Bowman_2006_5-1" class="reference"><a href="#cite_note-Bowman_2006-5"><span class="cite-bracket">[</span>5<span class="cite-bracket">]</span></a></sup> </p> <figure class="mw-halign-right" typeof="mw:File/Thumb"><a href="/wiki/File:Neuromuscularnondepolarizingagent.gif" class="mw-file-description"><img src="//upload.wikimedia.org/wikipedia/commons/thumb/7/75/Neuromuscularnondepolarizingagent.gif/240px-Neuromuscularnondepolarizingagent.gif" decoding="async" width="240" height="207" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/7/75/Neuromuscularnondepolarizingagent.gif/360px-Neuromuscularnondepolarizingagent.gif 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/7/75/Neuromuscularnondepolarizingagent.gif/480px-Neuromuscularnondepolarizingagent.gif 2x" data-file-width="1142" data-file-height="985" /></a><figcaption><a href="/wiki/Mind_Map" class="mw-redirect" title="Mind Map">Mind Map</a> showing a summary of <b>Neuromuscular nondepolarizing agent</b></figcaption></figure> <p>Below are some more common agents that act as <a href="/wiki/Competitive_antagonist" class="mw-redirect" title="Competitive antagonist">competitive antagonists</a> against acetylcholine at the site of postsynaptic acetylcholine receptors. </p><p><a href="/wiki/Tubocurarine" class="mw-redirect" title="Tubocurarine">Tubocurarine</a>, found in <a href="/wiki/Curare" title="Curare">curare</a> of the South American plant Pareira, <i><a href="/wiki/Chondrodendron_tomentosum" title="Chondrodendron tomentosum">Chondrodendron tomentosum</a></i>, is the prototypical non-depolarizing neuromuscular blocker. It has a slow onset (<5 min) and a long <a href="/wiki/Duration_of_action" class="mw-redirect" title="Duration of action">duration of action</a> (30 mins). Side-effects include <a href="/wiki/Hypotension" title="Hypotension">hypotension</a>, which is partially explained by its effect of increasing <a href="/wiki/Histamine" title="Histamine">histamine</a> release, a <a href="/wiki/Vasodilator" class="mw-redirect" title="Vasodilator">vasodilator</a>,<sup id="cite_ref-pmid2429800_10-0" class="reference"><a href="#cite_note-pmid2429800-10"><span class="cite-bracket">[</span>10<span class="cite-bracket">]</span></a></sup> as well as its effect of blocking <a href="/wiki/Autonomic_ganglion" title="Autonomic ganglion">autonomic ganglia</a>.<sup id="cite_ref-pmid2682131_11-0" class="reference"><a href="#cite_note-pmid2682131-11"><span class="cite-bracket">[</span>11<span class="cite-bracket">]</span></a></sup> It is excreted in the <a href="/wiki/Urine" title="Urine">urine</a>. </p><p>This drug needs to block about 70–80% of the ACh receptors for neuromuscular conduction to fail, and hence for effective blockade to occur. At this stage, <a href="/wiki/End-plate_potential" title="End-plate potential">end-plate potentials</a> (EPPs) can still be detected, but are too small to reach the <a href="/wiki/Threshold_potential" title="Threshold potential">threshold potential</a> needed for activation of muscle fiber contraction. </p><p>The speed of onset depends on the potency of the drug, greater potency is associated with slower onset of block. Rocuronium, with an ED<sub>95</sub> of 0.3 mg/kg IV has a more rapid onset than Vecuronium with an ED<sub>95</sub> of 0.05mg/kg.<sup id="cite_ref-Uptodate_12-0" class="reference"><a href="#cite_note-Uptodate-12"><span class="cite-bracket">[</span>12<span class="cite-bracket">]</span></a></sup> Steroidal compounds, such as rocuronium and vecuronium, are intermediate-acting drugs while Pancuronium and <a href="/wiki/Pipecuronium_bromide" title="Pipecuronium bromide">pipecuronium</a> are long-acting drugs.<sup id="cite_ref-Uptodate_12-1" class="reference"><a href="#cite_note-Uptodate-12"><span class="cite-bracket">[</span>12<span class="cite-bracket">]</span></a></sup> </p> <table class="wikitable sortable"> <caption>Comparison of non-depolarizing neuromuscular blocking agents </caption> <tbody><tr> <th>Agent </th> <td><b>Time to onset</b> <br /> (seconds) </td> <td><b>Duration</b> <br /> (minutes) </td> <th>Side effects </th> <th>Clinical use </th> <td>Storage </td></tr> <tr> <td><a href="/wiki/Rapacuronium" class="mw-redirect" title="Rapacuronium">Rapacuronium</a> (Raplon) </td> <td> </td> <td> </td> <td><a href="/wiki/Bronchospasm" title="Bronchospasm">Bronchospasm</a> </td> <td>Withdrawn due to Bronchospasm risk </td></tr> <tr> <td><a href="/wiki/Mivacurium" class="mw-redirect" title="Mivacurium">Mivacurium</a> (Mivacron) </td> <td>90 </td> <td>12–18<sup id="cite_ref-Rang151_13-0" class="reference"><a href="#cite_note-Rang151-13"><span class="cite-bracket">[</span>13<span class="cite-bracket">]</span></a></sup> </td> <td> <ul><li><a href="/wiki/Hypotension" title="Hypotension">hypotension</a> (transiently), by release of histamine<sup id="cite_ref-Rang151_13-1" class="reference"><a href="#cite_note-Rang151-13"><span class="cite-bracket">[</span>13<span class="cite-bracket">]</span></a></sup></li></ul> </td> <td>No longer manufactured secondary to marketing, manufacturing, and financial concerns </td> <td>refrigerated </td></tr> <tr> <td><a href="/wiki/Atracurium" class="mw-redirect" title="Atracurium">Atracurium</a> (Tracrium) </td> <td>90 </td> <td>30 min or less<sup id="cite_ref-Rang151_13-2" class="reference"><a href="#cite_note-Rang151-13"><span class="cite-bracket">[</span>13<span class="cite-bracket">]</span></a></sup> </td> <td> <ul><li><a href="/wiki/Hypotension" title="Hypotension">hypotension</a>, transiently,<sup id="cite_ref-Rang151_13-3" class="reference"><a href="#cite_note-Rang151-13"><span class="cite-bracket">[</span>13<span class="cite-bracket">]</span></a></sup> by release of histamine</li> <li>Toxic metabolite called <a href="/wiki/Laudanosine" title="Laudanosine">laudanosine</a>, greater accumulation in individuals with renal failure</li></ul> </td> <td>widely<sup id="cite_ref-Rang151_13-4" class="reference"><a href="#cite_note-Rang151-13"><span class="cite-bracket">[</span>13<span class="cite-bracket">]</span></a></sup> </td> <td>refrigerated </td></tr> <tr> <td><a href="/wiki/Doxacurium" class="mw-redirect" title="Doxacurium">Doxacurium</a> (Nuromax) </td> <td> </td> <td>long<sup id="cite_ref-Rang151_13-5" class="reference"><a href="#cite_note-Rang151-13"><span class="cite-bracket">[</span>13<span class="cite-bracket">]</span></a></sup> </td> <td> <ul><li><a href="/wiki/Hypotension" title="Hypotension">hypotension</a>, transiently,<sup id="cite_ref-Rang151_13-6" class="reference"><a href="#cite_note-Rang151-13"><span class="cite-bracket">[</span>13<span class="cite-bracket">]</span></a></sup> by release of histamine</li> <li>Harmful metabolite called <a href="/wiki/Laudanosine" title="Laudanosine">laudanosine</a> (lowering seizure threshold); greater accumulation in individuals with renal failure</li></ul> </td> <td> </td> <td> </td></tr> <tr> <td><a href="/wiki/Cisatracurium" class="mw-redirect" title="Cisatracurium">Cisatracurium</a> (Nimbex) </td> <td>90 </td> <td>60–80 </td> <td>does not cause release of histamine </td> <td> </td> <td>refrigerated </td></tr> <tr> <td><a href="/wiki/Vecuronium" class="mw-redirect" title="Vecuronium">Vecuronium</a> (Norcuron) </td> <td>60 </td> <td>30–40<sup id="cite_ref-Rang151_13-7" class="reference"><a href="#cite_note-Rang151-13"><span class="cite-bracket">[</span>13<span class="cite-bracket">]</span></a></sup> </td> <td>Few,<sup id="cite_ref-Rang151_13-8" class="reference"><a href="#cite_note-Rang151-13"><span class="cite-bracket">[</span>13<span class="cite-bracket">]</span></a></sup> may cause prolonged paralysis<sup id="cite_ref-Rang151_13-9" class="reference"><a href="#cite_note-Rang151-13"><span class="cite-bracket">[</span>13<span class="cite-bracket">]</span></a></sup> and promote muscarinic block </td> <td>widely<sup id="cite_ref-Rang151_13-10" class="reference"><a href="#cite_note-Rang151-13"><span class="cite-bracket">[</span>13<span class="cite-bracket">]</span></a></sup> </td> <td>non-refrigerated </td></tr> <tr> <td><a href="/wiki/Rocuronium" class="mw-redirect" title="Rocuronium">Rocuronium</a> (Zemuron) </td> <td>75 </td> <td>45–70<sup class="noprint Inline-Template Template-Fact" style="white-space:nowrap;">[<i><a href="/wiki/Wikipedia:Citation_needed" title="Wikipedia:Citation needed"><span title="This claim needs references to reliable sources. (March 2010)">citation needed</span></a></i>]</sup> </td> <td>may promote muscarinic block </td> <td> </td> <td>non-refrigerated </td></tr> <tr> <td><a href="/wiki/Pancuronium" class="mw-redirect" title="Pancuronium">Pancuronium</a> (Pavulon) </td> <td>90 </td> <td>180 or more<sup class="noprint Inline-Template Template-Fact" style="white-space:nowrap;">[<i><a href="/wiki/Wikipedia:Citation_needed" title="Wikipedia:Citation needed"><span title="This claim needs references to reliable sources. (March 2010)">citation needed</span></a></i>]</sup> </td> <td> <ul><li><a href="/wiki/Tachycardia" title="Tachycardia">tachycardia</a> (slight)<sup id="cite_ref-Rang151_13-11" class="reference"><a href="#cite_note-Rang151-13"><span class="cite-bracket">[</span>13<span class="cite-bracket">]</span></a></sup></li></ul> <p>(no hypotension)<sup id="cite_ref-Rang151_13-12" class="reference"><a href="#cite_note-Rang151-13"><span class="cite-bracket">[</span>13<span class="cite-bracket">]</span></a></sup> </p> </td> <td>widely<sup id="cite_ref-Rang151_13-13" class="reference"><a href="#cite_note-Rang151-13"><span class="cite-bracket">[</span>13<span class="cite-bracket">]</span></a></sup> </td> <td>non-refrigerated </td></tr> <tr> <td><a href="/wiki/Tubocurarine" class="mw-redirect" title="Tubocurarine">Tubocurarine</a> (Jexin) </td> <td>300 or more<sup id="cite_ref-Rang151_13-14" class="reference"><a href="#cite_note-Rang151-13"><span class="cite-bracket">[</span>13<span class="cite-bracket">]</span></a></sup> </td> <td>60–120<sup id="cite_ref-Rang151_13-15" class="reference"><a href="#cite_note-Rang151-13"><span class="cite-bracket">[</span>13<span class="cite-bracket">]</span></a></sup> </td> <td> <ul><li><a href="/wiki/Hypotension" title="Hypotension">hypotension</a> (by <a href="/wiki/Ganglion-block" class="mw-redirect" title="Ganglion-block">ganglion-block</a> and histamine release)<sup id="cite_ref-Rang151_13-16" class="reference"><a href="#cite_note-Rang151-13"><span class="cite-bracket">[</span>13<span class="cite-bracket">]</span></a></sup></li> <li><a href="/wiki/Bronchoconstriction" title="Bronchoconstriction">Bronchoconstriction</a> (by histamine release)<sup id="cite_ref-Rang151_13-17" class="reference"><a href="#cite_note-Rang151-13"><span class="cite-bracket">[</span>13<span class="cite-bracket">]</span></a></sup></li></ul> </td> <td>rarely<sup id="cite_ref-Rang151_13-18" class="reference"><a href="#cite_note-Rang151-13"><span class="cite-bracket">[</span>13<span class="cite-bracket">]</span></a></sup> </td> <td> </td></tr> <tr> <td><a href="/wiki/Gallamine" class="mw-redirect" title="Gallamine">gallamine</a> (Flaxedil) </td> <td>300 or more<sup id="cite_ref-Rang151_13-19" class="reference"><a href="#cite_note-Rang151-13"><span class="cite-bracket">[</span>13<span class="cite-bracket">]</span></a></sup> </td> <td>60–120<sup id="cite_ref-Rang151_13-20" class="reference"><a href="#cite_note-Rang151-13"><span class="cite-bracket">[</span>13<span class="cite-bracket">]</span></a></sup> </td> <td> <ul><li><a href="/wiki/Tachycardia" title="Tachycardia">tachycardia</a></li></ul> </td> <td> </td> <td>non-refrigerated </td></tr> <tr> <td><a href="/wiki/Pipecuronium" class="mw-redirect" title="Pipecuronium">Pipecuronium</a> </td> <td>90 </td> <td>180 or more<sup class="noprint Inline-Template Template-Fact" style="white-space:nowrap;">[<i><a href="/wiki/Wikipedia:Citation_needed" title="Wikipedia:Citation needed"><span title="This claim needs references to reliable sources. (March 2010)">citation needed</span></a></i>]</sup> </td> <td> <ul><li><a href="/wiki/Tachycardia" title="Tachycardia">tachycardia</a> (slight)<sup id="cite_ref-Rang151_13-21" class="reference"><a href="#cite_note-Rang151-13"><span class="cite-bracket">[</span>13<span class="cite-bracket">]</span></a></sup></li></ul> <p>(no hypotension)<sup id="cite_ref-Rang151_13-22" class="reference"><a href="#cite_note-Rang151-13"><span class="cite-bracket">[</span>13<span class="cite-bracket">]</span></a></sup> </p> </td> <td> </td> <td>non-refrigerated </td></tr></tbody></table> <table class="wikitable" style="text-align: center"> <caption>Comparison of properties of nondepolarising neuromuscular blocking agents.<sup id="cite_ref-book_14-0" class="reference"><a href="#cite_note-book-14"><span class="cite-bracket">[</span>14<span class="cite-bracket">]</span></a></sup> </caption> <tbody><tr> <th>Drug</th> <th>Elimination Site</th> <th>Clearance (mL/kg/min)</th> <th>Approximate Potency Relative to Tubocurarine </th></tr> <tr> <td>Isoquinoline derivatives </td> <td> </td></tr> <tr> <td>Tubocurarine</td> <td>Kidney (40%)</td> <td>2.3-2.4</td> <td>1 </td></tr> <tr> <td>Atracurium</td> <td>Spontaneous</td> <td>5-6</td> <td>1.5 </td></tr> <tr> <td>Cisatracurium</td> <td>Mostly Spontaneous</td> <td>2.7</td> <td>1.5 </td></tr> <tr> <td>Doxacurium</td> <td>Kidney</td> <td>2.7</td> <td>6 </td></tr> <tr> <td>Metocurine</td> <td>Kidney (40%)</td> <td>1.2</td> <td>4 </td></tr> <tr> <td>Mivacurium</td> <td>Plasma ChE<sup>2</sup></td> <td>70-95</td> <td>4 </td></tr> <tr> <td>Steroid derivatives </td></tr> <tr> <td>Pancuronium</td> <td>Kidney (80%)</td> <td>1.7-1.8</td> <td>6 </td></tr> <tr> <td>Pipecuronium</td> <td>Kidney (60%) and liver</td> <td>2.5-3.0</td> <td>6 </td></tr> <tr> <td>Rapacuronium</td> <td>Liver</td> <td>6-11</td> <td>0.4 </td></tr> <tr> <td>Rocuronium</td> <td>Liver (75-90%) and kidney</td> <td>2.9</td> <td>0.8 </td></tr> <tr> <td>Vecuronium</td> <td>Liver (75-90%) and kidney</td> <td>3-5.3</td> <td>6 </td></tr></tbody></table> <p>In larger clinical dose, some of the blocking agent can access the pore of the ion channel and cause blockage. This weakens neuromuscular transmission and diminishes the effect of <a href="/wiki/Acetylcholinesterase_inhibitors" class="mw-redirect" title="Acetylcholinesterase inhibitors">acetylcholinesterase inhibitors</a> (e.g. <a href="/wiki/Neostigmine" title="Neostigmine">neostigmine</a>).<sup id="cite_ref-book_14-1" class="reference"><a href="#cite_note-book-14"><span class="cite-bracket">[</span>14<span class="cite-bracket">]</span></a></sup> Nondepolarizing NBAs may also block prejunctional sodium channels which interfere with the mobilization of acetylcholine at the nerve ending.<sup id="cite_ref-book_14-2" class="reference"><a href="#cite_note-book-14"><span class="cite-bracket">[</span>14<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading3"><h3 id="Depolarizing_blocking_agents">Depolarizing blocking agents</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Neuromuscular-blocking_drug&action=edit&section=4" title="Edit section: Depolarizing blocking agents"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <figure class="mw-halign-right" typeof="mw:File/Thumb"><a href="/wiki/File:Neuromusculardepolarizingagent.gif" class="mw-file-description"><img src="//upload.wikimedia.org/wikipedia/commons/thumb/2/24/Neuromusculardepolarizingagent.gif/240px-Neuromusculardepolarizingagent.gif" decoding="async" width="240" height="218" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/2/24/Neuromusculardepolarizingagent.gif/360px-Neuromusculardepolarizingagent.gif 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/2/24/Neuromusculardepolarizingagent.gif/480px-Neuromusculardepolarizingagent.gif 2x" data-file-width="1060" data-file-height="963" /></a><figcaption><a href="/wiki/Mind_Map" class="mw-redirect" title="Mind Map">Mind Map</a> showing a summary of <b>Neuromuscular depolarizing agent</b></figcaption></figure> <p>A <b>depolarizing neuromuscular blocking agent</b> is a form of <a href="/wiki/Neuromuscular_blocker" class="mw-redirect" title="Neuromuscular blocker">neuromuscular blocker</a> that depolarizes the <a href="/wiki/Motor_end_plate" class="mw-redirect" title="Motor end plate">motor end plate</a>.<sup id="cite_ref-15" class="reference"><a href="#cite_note-15"><span class="cite-bracket">[</span>15<span class="cite-bracket">]</span></a></sup> An example is <a href="/wiki/Succinylcholine" class="mw-redirect" title="Succinylcholine">succinylcholine</a>. Depolarizing blocking agents work by depolarizing the plasma membrane of the muscle fiber, similar to <a href="/wiki/Acetylcholine" title="Acetylcholine">acetylcholine</a>. However, these agents are more resistant to degradation by <a href="/wiki/Acetylcholinesterase" title="Acetylcholinesterase">acetylcholinesterase</a>, the enzyme responsible for degrading acetylcholine, and can thus more persistently depolarize the muscle fibers. This differs from acetylcholine, which is rapidly degraded and only transiently depolarizes the muscle. </p><p>There are two phases to the depolarizing block. During phase I (<i>depolarizing phase</i>), succinylcholine interacts with nicotinic receptor to open the channel and cause <a href="/wiki/Depolarization" title="Depolarization">depolarization</a> of the <a href="/wiki/End_plate" class="mw-redirect" title="End plate">end plate</a>, which later spread to and result in depolarization of adjacent membranes. As a result, there is disorganisation of contraction of muscle motor unit.<sup id="cite_ref-book_14-3" class="reference"><a href="#cite_note-book-14"><span class="cite-bracket">[</span>14<span class="cite-bracket">]</span></a></sup> This causes muscular <a href="/wiki/Fasciculation" title="Fasciculation">fasciculations</a> (muscle twitches) while they are depolarizing the muscle fibers. Eventually, after sufficient depolarization has occurred, phase II (<i>desensitizing phase</i>) sets in and the muscle is no longer responsive to acetylcholine released by the <a href="/wiki/Motoneuron" class="mw-redirect" title="Motoneuron">motoneurons</a>.<sup id="cite_ref-book_14-4" class="reference"><a href="#cite_note-book-14"><span class="cite-bracket">[</span>14<span class="cite-bracket">]</span></a></sup> At this point, full neuromuscular block has been achieved. Phase I block effect can be increased by <a href="/wiki/Cholinesterase_inhibitors" class="mw-redirect" title="Cholinesterase inhibitors">cholinesterase inhibitors</a> which further delay the action of metabolism and removal by cholinesterase.<sup id="cite_ref-book_14-5" class="reference"><a href="#cite_note-book-14"><span class="cite-bracket">[</span>14<span class="cite-bracket">]</span></a></sup> </p><p>Under continuous exposure to succinylcholine, the initial end plate depolarization is reduced, and repolarisation process is initiated.<sup id="cite_ref-book_14-6" class="reference"><a href="#cite_note-book-14"><span class="cite-bracket">[</span>14<span class="cite-bracket">]</span></a></sup> As a result of the widespread sustained depolarization the synapses ultimately begin <a href="/wiki/Repolarization" title="Repolarization">repolarization</a>. Once repolarized, the membrane is still less susceptible to additional depolarization (phase II block).<sup id="cite_ref-book_14-7" class="reference"><a href="#cite_note-book-14"><span class="cite-bracket">[</span>14<span class="cite-bracket">]</span></a></sup> </p><p>The prototypical depolarizing blocking drug is <a href="/wiki/Succinylcholine" class="mw-redirect" title="Succinylcholine">succinylcholine</a> (suxamethonium). It is the only such drug used clinically. It has a rapid onset (30 seconds) but very short duration of action (5–10 minutes) because of hydrolysis by various cholinesterases (such as <a href="/wiki/Butyrylcholinesterase" title="Butyrylcholinesterase">butyrylcholinesterase</a> in the blood). The patient will experience <a href="/wiki/Fasciculation" title="Fasciculation">fasciculation</a> due to the depolarisation of muscle neurone fibres and seconds later, <a href="/wiki/Flaccid_paralysis" title="Flaccid paralysis">flaccid paralysis</a> will occur.<sup id="cite_ref-Uptodate_12-2" class="reference"><a href="#cite_note-Uptodate-12"><span class="cite-bracket">[</span>12<span class="cite-bracket">]</span></a></sup> Succinylcholine was originally known as diacetylcholine because structurally it is composed of two acetylcholine molecules joined with a methyl group. <a href="/wiki/Decamethonium" title="Decamethonium">Decamethonium</a> is sometimes, but rarely, used in clinical practice. </p><p>It is indicated for rapid sequence intubation. </p> <div class="mw-heading mw-heading4"><h4 id="Dosing/onset_of_action"><span id="Dosing.2Fonset_of_action"></span>Dosing/onset of action</h4><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Neuromuscular-blocking_drug&action=edit&section=5" title="Edit section: Dosing/onset of action"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>IV dose 1-1.5mg/kg or 3 to 5 x ED<sub>95</sub> </p><p>Paralysis occurs in one to two minutes. </p><p>Clinical duration of action (time from drug administration to recovery of single twich to 25% of baseline) is 7-12 minutes. </p><p>If IV access is unavailable, intramuscular administration 3-4mg/kg. Paralysis occurs at 4 minutes. </p><p>Use of succinylcholine infusion or repeated <a href="/wiki/Bolus_administration" class="mw-redirect" title="Bolus administration">bolus administration</a> increase the risk of Phase II block and prolonged paralysis. Phase II block occurs after large doses (>4mg/kg). This occurs when the post-synaptic membrane action potential returns to baseline in spite of the presence of succinylcholine and causes continued activation of nicotinic acetylcholine receptors.<sup id="cite_ref-Uptodate_12-3" class="reference"><a href="#cite_note-Uptodate-12"><span class="cite-bracket">[</span>12<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading3"><h3 id="Comparison_of_drugs">Comparison of drugs</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Neuromuscular-blocking_drug&action=edit&section=6" title="Edit section: Comparison of drugs"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>The main difference is in the reversal of these two types of neuromuscular-blocking drugs. </p> <ul><li>Non-depolarizing blockers are reversed by <a href="/wiki/Acetylcholinesterase_inhibitor" title="Acetylcholinesterase inhibitor">acetylcholinesterase inhibitor</a> drugs since non-depolarizing blockers are competitive antagonists at the ACh receptor so can be reversed by increases in ACh.</li> <li>The depolarizing blockers already have ACh-like actions, so these agents have prolonged effect under the influence of acetylcholinesterase inhibitors. Administration of depolarizing blockers initially produces <i>fasciculations</i> (a sudden twitch just before paralysis occurs). This is due to depolarization of the muscle. Also, post-operative pain is associated with depolarizing blockers.</li></ul> <p>The <i>tetanic fade</i> is the failure of muscles to maintain a fused <a href="/wiki/Tetany" title="Tetany">tetany</a> at sufficiently high frequencies of electrical stimulation. </p> <ul><li>Non-depolarizing blockers have this effect on patients, probably by an effect on presynaptic receptors.<sup id="cite_ref-Rang&Dale6th_16-0" class="reference"><a href="#cite_note-Rang&Dale6th-16"><span class="cite-bracket">[</span>16<span class="cite-bracket">]</span></a></sup></li> <li>Depolarizing blockers do not cause the tetanic fade. However, a clinically similar manifestation called Phase II block occurs with repeated doses of suxamethonium.</li></ul> <p>This discrepancy is diagnostically useful in case of intoxication of an unknown neuromuscular-blocking drug.<sup id="cite_ref-Rang&Dale6th_16-1" class="reference"><a href="#cite_note-Rang&Dale6th-16"><span class="cite-bracket">[</span>16<span class="cite-bracket">]</span></a></sup> </p> <table class="wikitable" style="text-align: center"> <caption>Comparison of a typical nondepolarizing muscle relexant (tubocarine) and a depolarizing muscle relexant (succinylcholine).<sup id="cite_ref-book_14-8" class="reference"><a href="#cite_note-book-14"><span class="cite-bracket">[</span>14<span class="cite-bracket">]</span></a></sup> </caption> <tbody><tr> <th rowspan="2"></th> <th rowspan="2">Tubocurarine</th> <th colspan="2">Succinylcholine </th></tr> <tr> <th>Phase I</th> <th>Phase II </th></tr> <tr> <td>Administration of tubocurarine</td> <td>Additive</td> <td>Antagonistic</td> <td>Augmented </td></tr> <tr> <td>Administration of succinylcholine</td> <td>Antagonistic</td> <td>Additive</td> <td>Augmented </td></tr> <tr> <td>Effect of neostigmine</td> <td>Antagonistic</td> <td>Augmented</td> <td>Antagonistic </td></tr> <tr> <td>Initial excitatory effect on skeletal muscle</td> <td>None</td> <td>Fasciculations</td> <td>None </td></tr> <tr> <td>Response to a tetanic stimulus</td> <td>Un-sustained <p>(fade) </p> </td> <td>sustained <p>(not fade) </p> </td> <td>Un-sustained <p>(fade) </p> </td></tr> <tr> <td>Post-tetanic facilitation</td> <td>Yes</td> <td>No</td> <td>Yes </td></tr> <tr> <td>Rate of recovery</td> <td>30-60 min</td> <td>4-8 min</td> <td>> 20 min </td></tr></tbody></table> <div class="mw-heading mw-heading2"><h2 id="Physiology_at_the_Neuromuscular_Junction">Physiology at the Neuromuscular Junction</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Neuromuscular-blocking_drug&action=edit&section=7" title="Edit section: Physiology at the Neuromuscular Junction"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>Neuromuscular blocking agents exert their effect by modulating the signal transmission in skeletal muscles. An action potential is, in other words, a depolarisation in neurone membrane due to a change in membrane potential greater than the <a href="/wiki/Threshold_potential" title="Threshold potential">threshold potential</a> leads to an electrical impulse generation. The electrical impulse travels along the pre-synaptic neurone axon to synapse with the muscle at the neuromuscular junction (NMJ) to cause muscle contraction.<sup id="cite_ref-:0_17-0" class="reference"><a href="#cite_note-:0-17"><span class="cite-bracket">[</span>17<span class="cite-bracket">]</span></a></sup> </p><p>When the action potential reaches the axon terminal, it triggers the opening of the <a href="/wiki/Calcium_ion_channel" class="mw-redirect" title="Calcium ion channel">calcium ion gated channels</a>, which causes the influx of Ca<sup>2+</sup>. Ca<sup>2+</sup> will stimulate the release of neurotransmitter in the neurotransmitter containing vesicles by <a href="/wiki/Exocytosis" title="Exocytosis">exocytosis</a> (vesicle fuses with the pre-synpatic membrane).<sup id="cite_ref-:0_17-1" class="reference"><a href="#cite_note-:0-17"><span class="cite-bracket">[</span>17<span class="cite-bracket">]</span></a></sup> </p><p>The neurotransmitter, acetylcholine(ACh) binds to the nicotinic receptors on the motor end plate, which is a specialised area of the muscle fibre's post-synaptic membrane. This binding causes the nicotinic receptor channels to open and allow the influx of Na<sup>+</sup> into the muscle fibre.<sup id="cite_ref-:0_17-2" class="reference"><a href="#cite_note-:0-17"><span class="cite-bracket">[</span>17<span class="cite-bracket">]</span></a></sup> </p><p>Fifty percent of the released ACh is hydrolysed by acetylcholinesterase (AChE) and the remaining bind to the nicotinic receptors on the motor end plate. When ACh is degraded by AChE, the receptors are no longer stimulated and the muscle cannot be depolarized.<sup id="cite_ref-:0_17-3" class="reference"><a href="#cite_note-:0-17"><span class="cite-bracket">[</span>17<span class="cite-bracket">]</span></a></sup> </p><p>If enough Na<sup>+</sup> enter the muscle fibre, it causes an increase in the membrane potential from its <a href="/wiki/Resting_potential" title="Resting potential">resting potential</a> of -95mV to -50mV (above the threshold potential -55mV) which causes an action potential to spread throughout the fibre. This potential travels along the surface of the <a href="/wiki/Sarcolemma" title="Sarcolemma">sarcolemma</a>. The sarcolemma is an excitable membrane that surrounds the contractile structures known as <a href="/wiki/Myofibrils" class="mw-redirect" title="Myofibrils">myofibrils</a> that are located deep in the muscle fibre. For the action potential to reach the myofibrils, the action potential travels along the <a href="/wiki/Transverse_tubules" class="mw-redirect" title="Transverse tubules">transverse tubules</a> (T-tubules) that connects the sarcolemma and center of the fibre.<sup id="cite_ref-:0_17-4" class="reference"><a href="#cite_note-:0-17"><span class="cite-bracket">[</span>17<span class="cite-bracket">]</span></a></sup> </p><p>Later, action potential reaches the <a href="/wiki/Sarcoplasmic_reticulum" title="Sarcoplasmic reticulum">sarcoplasmic reticulum</a> which stores the Ca<sup>2+</sup> needed for muscle contraction and causes Ca<sup>2+</sup> to be released from the sarcoplasmic reticulum.<sup id="cite_ref-:0_17-5" class="reference"><a href="#cite_note-:0-17"><span class="cite-bracket">[</span>17<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading2"><h2 id="Mechanism_of_action">Mechanism of action</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Neuromuscular-blocking_drug&action=edit&section=8" title="Edit section: Mechanism of action"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <figure typeof="mw:File/Thumb"><a href="/wiki/File:Acetylcholine_nicotinic_receptor_binding.svg" class="mw-file-description"><img src="//upload.wikimedia.org/wikipedia/commons/thumb/5/5f/Acetylcholine_nicotinic_receptor_binding.svg/200px-Acetylcholine_nicotinic_receptor_binding.svg.png" decoding="async" width="200" height="190" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/5/5f/Acetylcholine_nicotinic_receptor_binding.svg/300px-Acetylcholine_nicotinic_receptor_binding.svg.png 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/5/5f/Acetylcholine_nicotinic_receptor_binding.svg/400px-Acetylcholine_nicotinic_receptor_binding.svg.png 2x" data-file-width="721" data-file-height="685" /></a><figcaption>Fig.1 A simple illustration of how two <a href="/wiki/Acetylcholine" title="Acetylcholine">acetylcholine</a> molecules bind to its receptive sites on the nicotinic receptor</figcaption></figure><p>Quaternary muscle relaxants bind to the <a href="/wiki/Nicotinic_acetylcholine_receptor" title="Nicotinic acetylcholine receptor">nicotinic acetylcholine receptor</a> and inhibit or interfere with the binding and effect of <a href="/wiki/Acetylcholine" title="Acetylcholine">ACh</a> to the <a href="/wiki/Receptor_(biochemistry)" title="Receptor (biochemistry)">receptor</a>. Each <a href="/wiki/Acetylcholine_receptor" title="Acetylcholine receptor">ACh-receptor</a> has two receptive sites and activation of the receptor requires binding to both of them. Each receptor site is located at one of the two α-subunits of the receptor. Each receptive site has two subsites, an <a href="/wiki/Anionic" class="mw-redirect" title="Anionic">anionic</a> site that binds to the <a href="/wiki/Cationic" class="mw-redirect" title="Cationic">cationic</a> <a href="/wiki/Quaternary_ammonium" class="mw-redirect" title="Quaternary ammonium">ammonium</a> head and a site that binds to the blocking agent by donating a <a href="/wiki/Hydrogen_bond" title="Hydrogen bond">hydrogen bond</a>.<sup id="cite_ref-Bowman_2006_5-2" class="reference"><a href="#cite_note-Bowman_2006-5"><span class="cite-bracket">[</span>5<span class="cite-bracket">]</span></a></sup> </p><p><b>Non-depolarizing agents</b> A decrease in binding of acetylcholine leads to a decrease in its effect and <a href="/wiki/Neuron" title="Neuron">neuron</a> transmission to the <a href="/wiki/Muscle" title="Muscle">muscle</a> is less likely to occur. It is generally accepted that non-depolarizing agents block by acting as reversible competitive <a href="/wiki/Enzyme_inhibitor" title="Enzyme inhibitor">inhibitors</a>. That is, they bind to the receptor as <a href="/wiki/Receptor_antagonist" title="Receptor antagonist">antagonists</a> and that leaves fewer receptors available for acetylcholine to bind.<sup id="cite_ref-Bowman_2006_5-3" class="reference"><a href="#cite_note-Bowman_2006-5"><span class="cite-bracket">[</span>5<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-L.L_Brunton,_J.S.Lazo,_K.L.Parker_2006_18-0" class="reference"><a href="#cite_note-L.L_Brunton,_J.S.Lazo,_K.L.Parker_2006-18"><span class="cite-bracket">[</span>18<span class="cite-bracket">]</span></a></sup> </p><p><b>Depolarizing agents</b> <a href="/wiki/Depolarizing" class="mw-redirect" title="Depolarizing">Depolarizing</a> agents produce their block by binding to and activating the ACh receptor, at first causing muscle contraction, then paralysis. They bind to the receptor and cause depolarization by opening channels just like acetylcholine does. This causes repetitive excitation that lasts longer than a normal acetylcholine excitation and is most likely explained by the resistance of depolarizing agents to the <a href="/wiki/Enzyme" title="Enzyme">enzyme</a> <a href="/wiki/Acetylcholinesterase" title="Acetylcholinesterase">acetylcholinesterase</a>. The constant depolarization and triggering of the receptors keeps the endplate resistant to activation by acetylcholine. Therefore, a normal neuron transmission to muscle cannot cause contraction of the muscle because the endplate is depolarized and thereby the muscle paralysed.<sup id="cite_ref-Bowman_2006_5-4" class="reference"><a href="#cite_note-Bowman_2006-5"><span class="cite-bracket">[</span>5<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-L.L_Brunton,_J.S.Lazo,_K.L.Parker_2006_18-1" class="reference"><a href="#cite_note-L.L_Brunton,_J.S.Lazo,_K.L.Parker_2006-18"><span class="cite-bracket">[</span>18<span class="cite-bracket">]</span></a></sup> </p><p><b> Binding to the <a href="/wiki/Nicotinic_receptor" class="mw-redirect" title="Nicotinic receptor">nicotinic receptor</a> </b> Shorter molecules like acetylcholine need two molecules to activate the receptor, one at each receptive site. Decamethonium congeners, which prefer straight line conformations (their lowest energy state), usually span the two receptive sites with one molecule (binding inter-site). Longer congeners must bend when fitting receptive sites. </p><p>The greater energy a molecule needs to bend and fit usually results in lower potency.<sup id="cite_ref-Lee,_C.Jones,_T.Jones_2002_19-0" class="reference"><a href="#cite_note-Lee,_C.Jones,_T.Jones_2002-19"><span class="cite-bracket">[</span>19<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading2"><h2 id="Structural_and_conformational_action_relationship">Structural and conformational action relationship</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Neuromuscular-blocking_drug&action=edit&section=9" title="Edit section: Structural and conformational action relationship"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>Conformational study on <a href="/wiki/Muscle_relaxants" class="mw-redirect" title="Muscle relaxants">neuromuscular blocking drugs</a> is relatively new and developing. Traditional <a href="/wiki/Structure-activity_relationship" class="mw-redirect" title="Structure-activity relationship">SAR</a> studies do not specify environmental factors on molecules. <a href="/wiki/Computer" title="Computer">Computer</a>-based conformational searches assume that the molecules are <i><a href="/wiki/Vacuum" title="Vacuum">in vacuo</a></i>, which is not the case <i><a href="/wiki/In_vivo" title="In vivo">in vivo</a></i>. Solvation models take into account the effect of a solvent on the conformation of the molecule. However, no system of solvation can mimic the effect of the complex fluid composition of the body.<sup id="cite_ref-Lee_2003_20-0" class="reference"><a href="#cite_note-Lee_2003-20"><span class="cite-bracket">[</span>20<span class="cite-bracket">]</span></a></sup> </p><p>The division of <a href="/wiki/Muscle_relaxants" class="mw-redirect" title="Muscle relaxants">muscle relaxants</a> to rigid and non-rigid is at most qualitative. The <a href="/wiki/Energy" title="Energy">energy</a> required for conformational changes may give a more precise and quantitative picture. Energy required for reducing <a href="/wiki/Quaternary_ammonium" class="mw-redirect" title="Quaternary ammonium">onium</a> head distance in the longer muscle relaxant chains may quantify their ability to bend and fit its receptive sites.<sup id="cite_ref-Lee,_C.Jones,_T.Jones_2002_19-1" class="reference"><a href="#cite_note-Lee,_C.Jones,_T.Jones_2002-19"><span class="cite-bracket">[</span>19<span class="cite-bracket">]</span></a></sup> Using computers it is possible to calculate the lowest energy state conformer and thus most populated and best representing the molecule. This state is referred to as the global minimum. The global minimum for some simple molecules can be discovered quite easily with certainty. Such as for <a href="/wiki/Decamethonium" title="Decamethonium">decamethonium</a> the straight line conformer is clearly the lowest energy state. Some molecules, on the other hand, have many rotatable bonds and their global minimum can only be approximated.<sup id="cite_ref-Lee_2003_20-1" class="reference"><a href="#cite_note-Lee_2003-20"><span class="cite-bracket">[</span>20<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading3"><h3 id="Molecular_length_and_rigidity">Molecular length and rigidity</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Neuromuscular-blocking_drug&action=edit&section=10" title="Edit section: Molecular length and rigidity"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <figure typeof="mw:File/Thumb"><a href="/wiki/File:Decamethonium_binding_acth-receptor.svg" class="mw-file-description"><img src="//upload.wikimedia.org/wikipedia/commons/thumb/e/ef/Decamethonium_binding_acth-receptor.svg/350px-Decamethonium_binding_acth-receptor.svg.png" decoding="async" width="350" height="333" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/e/ef/Decamethonium_binding_acth-receptor.svg/525px-Decamethonium_binding_acth-receptor.svg.png 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/e/ef/Decamethonium_binding_acth-receptor.svg/700px-Decamethonium_binding_acth-receptor.svg.png 2x" data-file-width="721" data-file-height="685" /></a><figcaption>Fig.2 A simple illustration of how <a href="/wiki/Decamethonium" title="Decamethonium">decamethonium</a> binds to the nicotinic receptor. The onium heads bind to two separate subunits of the ion-channel</figcaption></figure><p>Neuromuscular blocking agents need to fit in a space close to 2 nanometres, which resembles the molecular length of decamethonium.<sup id="cite_ref-Lee,_C.Jones,_T.Jones_2002_19-2" class="reference"><a href="#cite_note-Lee,_C.Jones,_T.Jones_2002-19"><span class="cite-bracket">[</span>19<span class="cite-bracket">]</span></a></sup> Some molecules of decamethonium congeners may bind only to one receptive site. Flexible molecules have a greater chance of fitting receptive sites. However, the most populated conformation may not be the best-fitted one. Very flexible molecules are, in fact, weak neuromuscular inhibitors with flat dose-response curves. On the other hand, stiff or rigid molecules tend to fit well or not at all. If the lowest-energy conformation fits, the compound has high potency because there is a great concentration of molecules close to the lowest-energy conformation. Molecules can be thin but yet rigid.<sup id="cite_ref-Lee_2003_20-2" class="reference"><a href="#cite_note-Lee_2003-20"><span class="cite-bracket">[</span>20<span class="cite-bracket">]</span></a></sup> Decamethonium for example needs relatively high energy to change the <a href="/wiki/Nitrogen" title="Nitrogen">N</a>-<a href="/wiki/Nitrogen" title="Nitrogen">N</a> distance.<sup id="cite_ref-Lee,_C.Jones,_T.Jones_2002_19-3" class="reference"><a href="#cite_note-Lee,_C.Jones,_T.Jones_2002-19"><span class="cite-bracket">[</span>19<span class="cite-bracket">]</span></a></sup> </p><p>In general, molecular rigidity contributes to potency, while size affects whether a muscle relaxant shows a <a href="/wiki/Polarization_(electrochemistry)" title="Polarization (electrochemistry)">polarizing</a> or a <a href="/wiki/Depolarizing" class="mw-redirect" title="Depolarizing">depolarizing</a> effect.<sup id="cite_ref-Lee_2001_6-1" class="reference"><a href="#cite_note-Lee_2001-6"><span class="cite-bracket">[</span>6<span class="cite-bracket">]</span></a></sup> <a href="/wiki/Cations" class="mw-redirect" title="Cations">Cations</a> must be able to flow through the trans-membrane tube of the <a href="/wiki/Ion_channel" title="Ion channel">ion-channel</a> to depolarize the endplate.<sup id="cite_ref-Lee_2003_20-3" class="reference"><a href="#cite_note-Lee_2003-20"><span class="cite-bracket">[</span>20<span class="cite-bracket">]</span></a></sup> Small molecules may be rigid and potent but unable to occupy or block the area between the receptive sites.<sup id="cite_ref-Lee_2001_6-2" class="reference"><a href="#cite_note-Lee_2001-6"><span class="cite-bracket">[</span>6<span class="cite-bracket">]</span></a></sup> Large molecules, on the other hand, may bind to both receptive sites and hinder depolarizing cations independent of whether the ion-channel is open or closed below. Having a <a href="/wiki/Lipophilic" class="mw-redirect" title="Lipophilic">lipophilic</a> surface pointed towards the synapse enhances this effect by repelling cations. The importance of this effect varies between different muscle relaxants and classifying depolarizing from non-depolarizing blocks is a complex issue. The onium heads are usually kept small and the chains connecting the heads usually keep the N-N distance at 10 N or O atoms. Keeping the distance in mind the structure of the chain can vary (double bonded, cyclohexyl, benzyl, etc.)<sup id="cite_ref-Lee_2003_20-4" class="reference"><a href="#cite_note-Lee_2003-20"><span class="cite-bracket">[</span>20<span class="cite-bracket">]</span></a></sup> </p><p><a href="/wiki/Succinylcholine" class="mw-redirect" title="Succinylcholine">Succinylcholine</a> has a 10-<a href="/wiki/Atom" title="Atom">atom</a> distance between its <a href="/wiki/Nitrogen" title="Nitrogen">N</a> atoms, like decamethonium. Yet it has been reported that it takes two molecules, as with acetylcholine, to open one <a href="/wiki/Nicotinic_acetylcholine_receptor" title="Nicotinic acetylcholine receptor">nicotinic ion channel</a>. The conformational explanation for this is that each <a href="/wiki/Acetylcholine" title="Acetylcholine">acetylcholine</a> moiety of succinylcholine prefers the <i>gauche</i> (bent, cis) state. The attraction between the N and <a href="/wiki/Oxygen" title="Oxygen">O</a> atoms is greater than the onium head repulsion. In this most populated state, the N-N distance is shorter than the optimal distance of ten carbon atoms and too short to occupy both receptive sites. This similarity between succinyl- and acetyl-choline also explains its acetylcholine-like side-effects.<sup id="cite_ref-Lee_2003_20-5" class="reference"><a href="#cite_note-Lee_2003-20"><span class="cite-bracket">[</span>20<span class="cite-bracket">]</span></a></sup> Comparing molecular lengths, the pachycurares <a href="/wiki/Dimethyltubocurarine" class="mw-redirect" title="Dimethyltubocurarine">dimethyltubocurarine</a> and d-tubocurarine both are very rigid and measure close to 1.8 nm in total length. <a href="/wiki/Pancuronium" class="mw-redirect" title="Pancuronium">Pancuronium</a> and <a href="/wiki/Vecuronium" class="mw-redirect" title="Vecuronium">vecuronium</a> measure 1.9 nm, whereas <a href="/wiki/Pipecuronium" class="mw-redirect" title="Pipecuronium">pipecuronium</a> is 2.1 nm. The potency of these compounds follows the same rank of order as their length. Likewise, the leptocurares prefer a similar length. Decamethonium, which measures 2 nm, is the most potent in its category, whereas C11 is slightly too long. <a href="/wiki/Gallamine" class="mw-redirect" title="Gallamine">Gallamine</a> despite having low bulk and rigidity is the most potent in its class, and it measures 1.9 nm.<sup id="cite_ref-Lee_2001_6-3" class="reference"><a href="#cite_note-Lee_2001-6"><span class="cite-bracket">[</span>6<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-Lee,_C.Jones,_T.Jones_2002_19-4" class="reference"><a href="#cite_note-Lee,_C.Jones,_T.Jones_2002-19"><span class="cite-bracket">[</span>19<span class="cite-bracket">]</span></a></sup> Based on this information one can conclude that the optimum length for neuromuscular blocking agents, depolarizing or not, should be 2 to 2.1 nm.<sup id="cite_ref-Lee_2003_20-6" class="reference"><a href="#cite_note-Lee_2003-20"><span class="cite-bracket">[</span>20<span class="cite-bracket">]</span></a></sup> </p><p>The CAR for long-chain bisquaternary tetrahydroisoquinolines like atracurium, cisatracurium, mivacurium, and doxacurium is hard to determine because of their bulky onium heads and large number of rotatable <a href="/wiki/Chemical_bond" title="Chemical bond">bonds</a> and <a href="/wiki/Chemical_group" class="mw-redirect" title="Chemical group">groups</a>. These agents must follow the same <a href="/wiki/Receptor_(biochemistry)" title="Receptor (biochemistry)">receptive</a> topology as others, which means that they do not fit between the receptive sites without bending.<sup id="cite_ref-Lee,_C.Jones,_T.Jones_2002_19-5" class="reference"><a href="#cite_note-Lee,_C.Jones,_T.Jones_2002-19"><span class="cite-bracket">[</span>19<span class="cite-bracket">]</span></a></sup> <a href="/wiki/Mivacurium" class="mw-redirect" title="Mivacurium">Mivacurium</a> for example has a molecular length of 3.6 nm when stretched out, far from the 2 to 2.1 nm optimum. Mivacurium, atracurium, and <a href="/wiki/Doxacurium" class="mw-redirect" title="Doxacurium">doxacurium</a> have greater N-N distance and molecular length than d-tubocurarine even when bent. To make them fit, they have flexible connections that give their onium heads a chance to position themselves beneficially. This bent N-N scenario probably does not apply to <a href="/wiki/Laudexium" class="mw-redirect" title="Laudexium">laudexium</a> and <a href="/w/index.php?title=Decamethylene_bisatropium&action=edit&redlink=1" class="new" title="Decamethylene bisatropium (page does not exist)">decamethylene bisatropium</a>, which prefer a straight conformation.<sup id="cite_ref-Lee_2003_20-7" class="reference"><a href="#cite_note-Lee_2003-20"><span class="cite-bracket">[</span>20<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading3"><h3 id="Beers_and_Reich's_law"><span id="Beers_and_Reich.27s_law"></span>Beers and Reich's law</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Neuromuscular-blocking_drug&action=edit&section=11" title="Edit section: Beers and Reich's law"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>It has been concluded that acetylcholine and related compounds must be in the <i><a href="/wiki/Gauche_effect" title="Gauche effect">gauche</a></i> (bent) configuration when bound to the nicotinic receptor.<sup id="cite_ref-Spivak_1989_21-0" class="reference"><a href="#cite_note-Spivak_1989-21"><span class="cite-bracket">[</span>21<span class="cite-bracket">]</span></a></sup> Beers and Reich's studies on cholinergic receptors in 1970 showed a relationship affecting whether a compound was <a href="/wiki/Muscarinic" class="mw-redirect" title="Muscarinic">muscarinic</a> or <a href="/wiki/Nicotinic" class="mw-redirect" title="Nicotinic">nicotinic</a>. They showed that the distance from the centre of the quaternary N atom to the <a href="/wiki/Van_der_Waals_radius" title="Van der Waals radius">van der Waals</a> extension of the respective O atom (or an equivalent H-bond acceptor) is a determining factor. If the distance is 0.44 nm, the compound shows muscarinic properties—and if the distance is 0.59 nm, nicotinic properties dominate.<sup id="cite_ref-Beers_1970_22-0" class="reference"><a href="#cite_note-Beers_1970-22"><span class="cite-bracket">[</span>22<span class="cite-bracket">]</span></a></sup>) </p> <div class="mw-heading mw-heading3"><h3 id="Rational_design">Rational design</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Neuromuscular-blocking_drug&action=edit&section=12" title="Edit section: Rational design"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>Pancuronium remains one of the few muscle relaxants logically and rationally designed from structure-action / effects relationship data. A <a href="/wiki/Steroid" title="Steroid">steroid</a> skeleton was chosen because of its appropriate size and rigidness. Acetylcholine moieties were inserted to increase receptor affinity. Although having many unwanted side-effects, a slow onset of action and recovery rate it was a big success and at the time the most potent <a href="/wiki/Neuromuscular_drug" title="Neuromuscular drug">neuromuscular drug</a> available. Pancuronium and some other neuromuscular blocking agents block <a href="/wiki/Muscarinic_receptor" class="mw-redirect" title="Muscarinic receptor">M2-receptors</a> and therefore affect the <a href="/wiki/Vagus_nerve" title="Vagus nerve">vagus nerve</a>, leading to <a href="/wiki/Hypotension" title="Hypotension">hypotension</a> and <a href="/wiki/Tachycardia" title="Tachycardia">tachycardia</a>. This muscarinic blocking effect is related to the acetylcholine moiety on the A ring on pancuronium. Making the N atom on the A ring tertiary, the ring loses its acetylcholine moiety, and the resulting compound, vecuronium, has nearly 100 times less affinity to muscarin receptors while maintaining its nicotinic affinity and a similar duration of action. Vecuronium is, therefore, free from cardiovascular effects.<sup id="cite_ref-Bowman_2006_5-5" class="reference"><a href="#cite_note-Bowman_2006-5"><span class="cite-bracket">[</span>5<span class="cite-bracket">]</span></a></sup> The D ring shows excellent properties validating Beers and Reich's rule with great precision. As a result, vecuronium has the greatest potency and specificity of all mono-quaternary compounds.<sup id="cite_ref-Lee_2003_20-8" class="reference"><a href="#cite_note-Lee_2003-20"><span class="cite-bracket">[</span>20<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading3"><h3 id="Potency">Potency</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Neuromuscular-blocking_drug&action=edit&section=13" title="Edit section: Potency"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>Two functional groups contribute significantly to <a href="/wiki/Aminosteroid" title="Aminosteroid">aminosteroidal</a> neuromuscular blocking potency, it is presumed to enable them to bind the receptor at two points. A bis-quaternary two point arrangement on A and D-ring (binding inter-site) or a D-ring acetylcholine moiety (binding at two points intra-site) are most likely to succeed. A third group can have variable effects.<sup id="cite_ref-Lee_2003_20-9" class="reference"><a href="#cite_note-Lee_2003-20"><span class="cite-bracket">[</span>20<span class="cite-bracket">]</span></a></sup> The quaternary and acetyl groups on the A and D ring of pipecuronium prevent it from binding intra-site (binding to two points at the same site). Instead, it must bind as bis-quaternary (inter-site).<sup id="cite_ref-Lee_2001_6-4" class="reference"><a href="#cite_note-Lee_2001-6"><span class="cite-bracket">[</span>6<span class="cite-bracket">]</span></a></sup> These structures are very dissimilar from acetylcholine and free pipecuronium from nicotinic or muscarinic side-effects linked to acetylcholine moiety. Also, they protect the molecule from hydrolysis by cholinesterases, which explain its nature of kidney excretion. The four <a href="/wiki/Methyl_group" title="Methyl group">methyl-groups</a> on the quaternary N atoms make it less lipophilic than most aminosteroids. This also affects pipecuroniums metabolism by resisting hepatic uptake, metabolism, and <a href="/wiki/Bile" title="Bile">biliary</a> excretion. The length of the molecule (2.1 nm, close to ideal) and its rigidness make pipecuronium the most potent and clean one-bulk bis-quaternary. Even though the N-N distance (1.6 nm) is far away from what is considered ideal, its onium heads are well-exposed, and the quaternary groups help to bring together the onium heads to the anionic centers of the receptors without chirality issues.<sup id="cite_ref-Lee_2003_20-10" class="reference"><a href="#cite_note-Lee_2003-20"><span class="cite-bracket">[</span>20<span class="cite-bracket">]</span></a></sup> </p><p>Adding more than two onium heads in general does not add to potency. Though the third onium head in gallamine seems to help position the two outside heads near the optimum molecular length, it can interfere unfavorably and gallamine turns out to be a weak muscle relaxant, like all multi-quaternary compounds. Considering acetylcholine a quaternizing group larger than methyl and an acyl group larger than acetyl would reduce the molecule's potency. The charged N and the <a href="/wiki/Carbonyl" class="mw-redirect" title="Carbonyl">carbonyl</a> O atoms are distanced from structures they bind to on receptive sites and, thus, decrease potency. The carbonyl O in vecuronium for example is thrust outward to appose the <a href="/wiki/Hydrogen_bond" title="Hydrogen bond">H-bond</a> donor of the receptive site. This also helps explain why gallamine, rocuronium, and rapacuronium are of relatively low potency.<sup id="cite_ref-Lee_2003_20-11" class="reference"><a href="#cite_note-Lee_2003-20"><span class="cite-bracket">[</span>20<span class="cite-bracket">]</span></a></sup> In general, methyl quaternization is optimal for potency but, opposing this rule, the trimethyl derivatives of gallamine are of lower potency than gallamine. The reason for this is that gallamine has a suboptimal N-N distance. Substituting the ethyl groups with methyl groups would make the molecular length also shorter than optimal. <a href="/wiki/Methoxy" class="mw-redirect" title="Methoxy">Methoxylation</a> of tetrahydroisoquinolinium agents seems to improve their potency. How methoxylation improves potency is still unclear. <a href="/wiki/Histamine" title="Histamine">Histamine</a> release is a common attribute of benzylisoquinolinium muscle relaxants. This problem generally decreases with increased potency and smaller doses. The need for larger doses increases the degree of this side-effect. Conformational or structural explanations for histamine release are not clear.<sup id="cite_ref-Lee_2003_20-12" class="reference"><a href="#cite_note-Lee_2003-20"><span class="cite-bracket">[</span>20<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading2"><h2 id="Pharmacokinetics">Pharmacokinetics</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Neuromuscular-blocking_drug&action=edit&section=14" title="Edit section: Pharmacokinetics"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p><b> Metabolism and Hofmann elimination </b> </p> <figure typeof="mw:File/Thumb"><a href="/wiki/File:Vecuroniumreceptor.JPG" class="mw-file-description"><img src="//upload.wikimedia.org/wikipedia/commons/thumb/1/1e/Vecuroniumreceptor.JPG/400px-Vecuroniumreceptor.JPG" decoding="async" width="400" height="378" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/1/1e/Vecuroniumreceptor.JPG 1.5x" data-file-width="498" data-file-height="470" /></a><figcaption>Fig.3 A simple illustration of how <a href="/wiki/Vecuronium_bromide" title="Vecuronium bromide">vecuronium</a> binds to the nicotinic receptor. Its D-ring binds to the receptor at two points and the lipophillic side of the molecule repels cations from flowing through the ion-channel</figcaption></figure><p><a href="/wiki/Acetyl" class="mw-redirect" title="Acetyl">Deacetylating</a> <a href="/wiki/Vecuronium" class="mw-redirect" title="Vecuronium">vecuronium</a> at position 3 results in a very active metabolite.<sup id="cite_ref-Caldwell_1994_23-0" class="reference"><a href="#cite_note-Caldwell_1994-23"><span class="cite-bracket">[</span>23<span class="cite-bracket">]</span></a></sup> In the case of <a href="/wiki/Rapacuronium" class="mw-redirect" title="Rapacuronium">rapacuronium</a> the 3-<a href="/wiki/Acetyl" class="mw-redirect" title="Acetyl">deacylated</a> <a href="/wiki/Metabolomics" title="Metabolomics">metabolite</a> is even more potent than rapacuronium. As long as the D-ring <a href="/wiki/Acetylcholine" title="Acetylcholine">acetylcholine</a> moiety is unchanged they retain their muscle relaxing effect. <a href="/wiki/Quaternary_ammonium_cation" title="Quaternary ammonium cation"><i>Mono</i>-quaternary</a> <a href="/wiki/Aminosteroid" title="Aminosteroid">aminosteroids</a> produced with <a href="/wiki/Acetyl" class="mw-redirect" title="Acetyl">deacylation</a> in position 17 on the other hand are generally weak muscle relaxants.<sup id="cite_ref-Lee_2003_20-13" class="reference"><a href="#cite_note-Lee_2003-20"><span class="cite-bracket">[</span>20<span class="cite-bracket">]</span></a></sup> In the development of <a href="/wiki/Atracurium" class="mw-redirect" title="Atracurium">atracurium</a> the main idea was to make use of <a href="/wiki/Hofmann_elimination" title="Hofmann elimination">Hofmann elimination</a> of the muscle relaxant <i><a href="/wiki/In_vivo" title="In vivo">in vivo</a></i>. When working with bisbenzyl-isoquinolinium types of molecules, inserting proper features into the molecule such as an appropriate <a href="/wiki/Electron" title="Electron">electron</a> withdrawing group then <a href="/wiki/Hofmann_elimination" title="Hofmann elimination">Hofmann elimination</a> should occur at conditions <i>in vivo</i>. Atracurium, the resulting <a href="/wiki/Molecule" title="Molecule">molecule</a>, breaks down spontaneously in the body to inactive <a href="/wiki/Chemical_compound" title="Chemical compound">compounds</a> and being especially useful in patients with <a href="/wiki/Kidney" title="Kidney">kidney</a> or <a href="/wiki/Liver" title="Liver">liver</a> failure. <a href="/wiki/Chemical_compound" title="Chemical compound"><i>Cis</i>-atracurium</a> is very similar to atracurium except it is more potent and has a weaker tendency to cause <a href="/wiki/Histamine" title="Histamine">histamine</a> release.<sup id="cite_ref-Bowman_2006_5-6" class="reference"><a href="#cite_note-Bowman_2006-5"><span class="cite-bracket">[</span>5<span class="cite-bracket">]</span></a></sup> </p><p><b>Structure relations to onset time</b> </p><p>The effect of structure on the <a href="/wiki/Onset_of_action" title="Onset of action">onset of action</a> is not very well known except that the time of onset appears inversely related to potency.<sup id="cite_ref-Kopman_1999_24-0" class="reference"><a href="#cite_note-Kopman_1999-24"><span class="cite-bracket">[</span>24<span class="cite-bracket">]</span></a></sup> In general <i>mono</i>-quaternary aminosteroids are faster than <a href="/wiki/Quaternary_ammonium_cation" title="Quaternary ammonium cation"><i>bis</i>-quaternary</a> compounds, which means they are also of lower potency. A possible explanation for this effect is that drug delivery and receptor binding are of a different timescale. Weaker muscle relaxants are given in larger doses so more molecules in the <a href="/wiki/Pharmacokinetics" title="Pharmacokinetics">central compartment</a> must diffuse into the <a href="/wiki/Pharmacokinetics" title="Pharmacokinetics">effect compartment</a>, which is the space within the mouth of the receptor, of the body. After delivery to the effect compartment then all <a href="/wiki/Molecules" class="mw-redirect" title="Molecules">molecules</a> act quickly.<sup id="cite_ref-Donati_2005_25-0" class="reference"><a href="#cite_note-Donati_2005-25"><span class="cite-bracket">[</span>25<span class="cite-bracket">]</span></a></sup> Therapeutically this relationship is very inconvenient because low potency, often meaning low specificity can decrease the safety margin thus increasing the chances of <a href="/wiki/Adverse_drug_reaction" title="Adverse drug reaction">side-effects</a>. In addition, even though low potency usually accelerates <a href="/wiki/Onset_of_action" title="Onset of action">onset of action</a>, it does not guaranty a fast onset. <a href="/wiki/Gallamine" class="mw-redirect" title="Gallamine">Gallamine</a>, for example, is weak and slow. When fast onset is necessary then <a href="/wiki/Succinylcholine" class="mw-redirect" title="Succinylcholine">succinylcholine</a> or <a href="/wiki/Rocuronium_bromide" title="Rocuronium bromide">rocuronium</a> are usually preferable.<sup id="cite_ref-Lee_2003_20-14" class="reference"><a href="#cite_note-Lee_2003-20"><span class="cite-bracket">[</span>20<span class="cite-bracket">]</span></a></sup> </p><p><b>Elimination</b> </p><p><a href="/wiki/Muscle_relaxants" class="mw-redirect" title="Muscle relaxants">Muscle relaxants</a> can have very different <a href="/wiki/Metabolomics" title="Metabolomics">metabolic pathways</a> and it is important that the drug does not accumulate if certain elimination pathways are not active, for example in <a href="/wiki/Kidney" title="Kidney">kidney</a> failure. </p> <div class="mw-heading mw-heading2"><h2 id="Medical_Use">Medical Use</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Neuromuscular-blocking_drug&action=edit&section=15" title="Edit section: Medical Use"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <div class="mw-heading mw-heading3"><h3 id="Endotracheal_intubation">Endotracheal intubation</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Neuromuscular-blocking_drug&action=edit&section=16" title="Edit section: Endotracheal intubation"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>Administration of neuromuscular blocking agents (NMBA) during <a href="/wiki/Anesthesia" title="Anesthesia">anesthesia</a> can facilitate <a href="/wiki/Endotracheal_intubation" class="mw-redirect" title="Endotracheal intubation">endotracheal intubation</a>.<sup id="cite_ref-Uptodate_12-4" class="reference"><a href="#cite_note-Uptodate-12"><span class="cite-bracket">[</span>12<span class="cite-bracket">]</span></a></sup> This can decrease the incidence of postintubation hoarseness and airway injury.<sup id="cite_ref-Uptodate_12-5" class="reference"><a href="#cite_note-Uptodate-12"><span class="cite-bracket">[</span>12<span class="cite-bracket">]</span></a></sup> </p><p>Short-acting neuromuscular blocking agents are chosen for endotracheal intubation for short procedures (< 30minutes), and neuromonitoring is required soon after intubation.<sup id="cite_ref-Uptodate_12-6" class="reference"><a href="#cite_note-Uptodate-12"><span class="cite-bracket">[</span>12<span class="cite-bracket">]</span></a></sup> Options include <a href="/wiki/Succinylcholine" class="mw-redirect" title="Succinylcholine">succinylcholine</a>, rocuronium or vecuronium if <a href="/wiki/Sugammadex" title="Sugammadex">sugammadex</a> is available for rapid reversal block.<sup id="cite_ref-Uptodate_12-7" class="reference"><a href="#cite_note-Uptodate-12"><span class="cite-bracket">[</span>12<span class="cite-bracket">]</span></a></sup> </p><p>Any short or intermediate acting neuromuscular blocking agents can be applied for endotracheal intubation for long procedures (≥ 30 minutes).<sup id="cite_ref-Uptodate_12-8" class="reference"><a href="#cite_note-Uptodate-12"><span class="cite-bracket">[</span>12<span class="cite-bracket">]</span></a></sup> Options include succinylcholine, rocuronium, vecuronium, <a href="/wiki/Mivacurium" class="mw-redirect" title="Mivacurium">mivacurium</a>, atracurium and <a href="/wiki/Cisatracurium" class="mw-redirect" title="Cisatracurium">cisatracurium</a>.<sup id="cite_ref-Uptodate_12-9" class="reference"><a href="#cite_note-Uptodate-12"><span class="cite-bracket">[</span>12<span class="cite-bracket">]</span></a></sup> The choice among these NMBA depends on availability, cost and patient parameters that affect <a href="/wiki/Drug_metabolism" title="Drug metabolism">drug metabolism</a>. </p><p>Intraoperative relaxation can be maintained as necessary with additional dose of nondepolarizing NMBA.<sup id="cite_ref-Uptodate_12-10" class="reference"><a href="#cite_note-Uptodate-12"><span class="cite-bracket">[</span>12<span class="cite-bracket">]</span></a></sup> </p><p>Among all NMBA, Succinylcholine establish the most stable and fastest intubating conditions, thus is considered as the preferred NMBA for rapid sequence induction and intubation (RSII).<sup id="cite_ref-Uptodate_12-11" class="reference"><a href="#cite_note-Uptodate-12"><span class="cite-bracket">[</span>12<span class="cite-bracket">]</span></a></sup> Alternatives for succinylcholine for RSII include high dose rocuronium (1.2mg/kg which is a 4 X ED95 dose), or avoidance of NMBAs with a high dose <a href="/wiki/Remifentanil" title="Remifentanil">remifentanil</a> intubation.<sup id="cite_ref-Uptodate_12-12" class="reference"><a href="#cite_note-Uptodate-12"><span class="cite-bracket">[</span>12<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading3"><h3 id="Facilitation_of_surgery">Facilitation of surgery</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Neuromuscular-blocking_drug&action=edit&section=17" title="Edit section: Facilitation of surgery"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>Nondepolarizing NMBAs can be used to induce muscle relaxation that improves surgical conditions, including <a href="/wiki/Laparoscopic" class="mw-redirect" title="Laparoscopic">laparoscopic</a>, <a href="/wiki/Robotic" class="mw-redirect" title="Robotic">robotic</a>, <a href="/wiki/Abdominal" class="mw-redirect" title="Abdominal">abdominal</a> and <a href="/wiki/Thoracic" class="mw-redirect" title="Thoracic">thoracic</a> procedures.<sup id="cite_ref-Uptodate_12-13" class="reference"><a href="#cite_note-Uptodate-12"><span class="cite-bracket">[</span>12<span class="cite-bracket">]</span></a></sup> It can reduce patient movement, muscle tone, breathing or coughing against ventilator and allow lower <a href="/wiki/Insufflation" title="Insufflation">insufflation</a> pressure during laparoscopy.<sup id="cite_ref-Uptodate_12-14" class="reference"><a href="#cite_note-Uptodate-12"><span class="cite-bracket">[</span>12<span class="cite-bracket">]</span></a></sup> Administration of NMBAs should be individualized according to patient’s parameters. However, many operations can be performed without the need to apply any NMBAs as adequate anesthesia during surgery can achieve many of the theoretical benefits of neuromuscular blockage.<sup id="cite_ref-Uptodate_12-15" class="reference"><a href="#cite_note-Uptodate-12"><span class="cite-bracket">[</span>12<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading2"><h2 id="Adverse_effects">Adverse effects</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Neuromuscular-blocking_drug&action=edit&section=18" title="Edit section: Adverse effects"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>Since these drugs may cause <a href="/wiki/Paralysis" title="Paralysis">paralysis</a> of the <a href="/wiki/Diaphragm_(anatomy)" class="mw-redirect" title="Diaphragm (anatomy)">diaphragm</a>, mechanical ventilation should be at hand to provide respiration. </p><p>In addition, these drugs may exhibit <a href="/wiki/Cardiovascular" class="mw-redirect" title="Cardiovascular">cardiovascular</a> effects, since they are not fully selective for the <a href="/wiki/Nicotinic_receptor" class="mw-redirect" title="Nicotinic receptor">nicotinic receptor</a> and hence may have effects on <a href="/wiki/Muscarinic_receptor" class="mw-redirect" title="Muscarinic receptor">muscarinic receptors</a>.<sup id="cite_ref-pmid2682131_11-1" class="reference"><a href="#cite_note-pmid2682131-11"><span class="cite-bracket">[</span>11<span class="cite-bracket">]</span></a></sup> If nicotinic receptors of the <a href="/wiki/Autonomic_ganglion" title="Autonomic ganglion">autonomic ganglia</a> or <a href="/wiki/Adrenal_medulla" title="Adrenal medulla">adrenal medulla</a> are blocked, these drugs may cause autonomic symptoms. Also, neuromuscular blockers may facilitate <a href="/wiki/Histamine" title="Histamine">histamine</a> release, which causes hypotension, <a href="/wiki/Flushing_(physiology)" title="Flushing (physiology)">flushing</a>, and tachycardia. </p><p>Succinylcholine may also trigger <a href="/wiki/Malignant_hyperthermia" title="Malignant hyperthermia">malignant hyperthermia</a> in rare cases in patients who may be susceptible. </p><p>In depolarizing the musculature, suxamethonium may trigger a transient release of large amounts of <a href="/wiki/Potassium" title="Potassium">potassium</a> from muscle fibers. This puts the patient at risk for life-threatening complications, such as <a href="/wiki/Hyperkalemia" title="Hyperkalemia">hyperkalemia</a> and <a href="/wiki/Cardiac_arrhythmia" class="mw-redirect" title="Cardiac arrhythmia">cardiac arrhythmias</a>. Other effects include <a href="/wiki/Myalgia" title="Myalgia">myalgia</a>, increased intragastric pressure, increased intraocular pressure, increased intracranial pressure, <a href="/wiki/Cardiac_dysrhythmias" class="mw-redirect" title="Cardiac dysrhythmias">cardiac dysrhythmias</a> (<a href="/wiki/Bradycardia" title="Bradycardia">bradycardia</a> is the most common type) and <a href="/wiki/Allergic_reactions" class="mw-redirect" title="Allergic reactions">allergic reactions</a>.<sup id="cite_ref-Uptodate_12-16" class="reference"><a href="#cite_note-Uptodate-12"><span class="cite-bracket">[</span>12<span class="cite-bracket">]</span></a></sup> As a result, it is contraindicated for patients with susceptibility to malignant hyperthermia, <a href="/wiki/Denervation" title="Denervation">denervating conditions</a>, major burns after 48 hours, and severe hyperkalemia. </p><p>For nondepolarizing NMBAs except vecuronium, pipecuronium, doxacurium, cisatracurium, rocuronium and rapacuronium, they produce certain extent of cardiovascular effect.<sup id="cite_ref-book_14-9" class="reference"><a href="#cite_note-book-14"><span class="cite-bracket">[</span>14<span class="cite-bracket">]</span></a></sup> Moreover, Tubocurarine can produce <a href="/wiki/Hypotension" title="Hypotension">hypotension</a> effect while Pancuronium can lead to moderate increase in heart rate and small increase in cardiac output with little or no increase in <a href="/wiki/Systemic_vascular_resistance" class="mw-redirect" title="Systemic vascular resistance">systemic vascular resistance</a>, which is unique in nondeploarizing NMBAs.<sup id="cite_ref-book_14-10" class="reference"><a href="#cite_note-book-14"><span class="cite-bracket">[</span>14<span class="cite-bracket">]</span></a></sup> </p><p>Certain drugs such as <a href="/wiki/Aminoglycoside" title="Aminoglycoside">aminoglycoside</a> antibiotics and <a href="/wiki/Polymyxin" title="Polymyxin">polymyxin</a> and some <a href="/wiki/Fluoroquinolones" class="mw-redirect" title="Fluoroquinolones">fluoroquinolones</a> also have neuromuscular blocking action as their side-effect.<sup id="cite_ref-26" class="reference"><a href="#cite_note-26"><span class="cite-bracket">[</span>26<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading2"><h2 id="Interactions">Interactions</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Neuromuscular-blocking_drug&action=edit&section=19" title="Edit section: Interactions"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>Some drugs enhance or inhibit the response to NMBAs which require the dosage adjustment guided by monitoring. </p> <div class="mw-heading mw-heading3"><h3 id="Combination_of_NMBAs">Combination of NMBAs</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Neuromuscular-blocking_drug&action=edit&section=20" title="Edit section: Combination of NMBAs"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>In some clinical circumstances, <a href="/wiki/Suxamethonium_chloride" title="Suxamethonium chloride">succinylcholine</a> may be administered before and after a nondepolarising NMBA or two different nondepolarising NMBAs are administered in sequence.<sup id="cite_ref-Uptodate_12-17" class="reference"><a href="#cite_note-Uptodate-12"><span class="cite-bracket">[</span>12<span class="cite-bracket">]</span></a></sup> Combining different NMBAs can result in different degrees of neuromuscular block and management should be guided with the use of a <a href="/wiki/Neuromuscular_monitoring" title="Neuromuscular monitoring">neuromuscular function monitor</a>. </p><p>The administration of nondepolarising neuromuscular blocking agent has an <a href="/wiki/Receptor_antagonist" title="Receptor antagonist">antagonistic effect</a> on the subsequent depolarising block induced by succinylcholine.<sup id="cite_ref-Uptodate_12-18" class="reference"><a href="#cite_note-Uptodate-12"><span class="cite-bracket">[</span>12<span class="cite-bracket">]</span></a></sup> If a nondepolarising NMBA is administered prior to succinycholine, the dose of succinylcholine must be increased. </p><p>The administration of succinylcholine on the subsequent administration of a nondepolarising neuromuscular block depends on the drug used. Studies have shown that administration of succinylcholien before a nondepolarising NMBA does not affect the potency of <a href="/wiki/Mivacurium_chloride" title="Mivacurium chloride">mivacurium</a> or <a href="/wiki/Rocuronium_bromide" title="Rocuronium bromide">rocuronium</a>.<sup id="cite_ref-Uptodate_12-19" class="reference"><a href="#cite_note-Uptodate-12"><span class="cite-bracket">[</span>12<span class="cite-bracket">]</span></a></sup> But for <a href="/wiki/Vecuronium_bromide" title="Vecuronium bromide">vecuronium</a> and <a href="/wiki/Cisatracurium_besilate" title="Cisatracurium besilate">cisatracurium</a>, it speeds up the onset, increases the potency and prolongs the duration of action.<sup id="cite_ref-Uptodate_12-20" class="reference"><a href="#cite_note-Uptodate-12"><span class="cite-bracket">[</span>12<span class="cite-bracket">]</span></a></sup> </p><p>Combining two nondepolarising NMBAs of the same chemical class (e.g. rocuronium and vecuronium) produces an additive effect, while combining two nondepolarising NMBAs of different chemical class (e.g. rocuronium and cisatracurium) produces a synergistic response.<sup id="cite_ref-Uptodate_12-21" class="reference"><a href="#cite_note-Uptodate-12"><span class="cite-bracket">[</span>12<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading3"><h3 id="Inhaled_anesthetics">Inhaled anesthetics</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Neuromuscular-blocking_drug&action=edit&section=21" title="Edit section: Inhaled anesthetics"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>Inhaled anesthetics inhibit nicotinic acetylcholine receptors (nAChRs) and potentiate neuromuscular blockage with nondepolarising NMBAs.<sup id="cite_ref-Uptodate_12-22" class="reference"><a href="#cite_note-Uptodate-12"><span class="cite-bracket">[</span>12<span class="cite-bracket">]</span></a></sup> It depends on the type of <a href="/wiki/Volatile_anesthetic" class="mw-redirect" title="Volatile anesthetic">volatile anesthetic</a> (<a href="/wiki/Desflurane" title="Desflurane">desflurane</a> > <a href="/wiki/Sevoflurane" title="Sevoflurane">sevoflurane</a> > <a href="/wiki/Isoflurane" title="Isoflurane">isoflurane</a> > <a href="/wiki/Nitrous_oxide" title="Nitrous oxide">nitrous oxide</a>), the concentration and the duration of exposure.<sup id="cite_ref-Uptodate_12-23" class="reference"><a href="#cite_note-Uptodate-12"><span class="cite-bracket">[</span>12<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading3"><h3 id="Antibiotics">Antibiotics</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Neuromuscular-blocking_drug&action=edit&section=22" title="Edit section: Antibiotics"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p><a href="/wiki/Tetracycline" title="Tetracycline">Tetracycline</a>, <a href="/wiki/Aminoglycosides" class="mw-redirect" title="Aminoglycosides">aminoglycosides</a>, <a href="/wiki/Polymyxins" class="mw-redirect" title="Polymyxins">polymyxins</a> and <a href="/wiki/Clindamycin" title="Clindamycin">clindamycin</a> potentiate neuromuscular blockage by inhibiting ACh release or <a href="/wiki/Desensitization_(medicine)" title="Desensitization (medicine)">desensitisation</a> of post-synpatic nAChRs to ACh.<sup id="cite_ref-Uptodate_12-24" class="reference"><a href="#cite_note-Uptodate-12"><span class="cite-bracket">[</span>12<span class="cite-bracket">]</span></a></sup> This interaction happens mostly during maintenance of anesthesia. As antibiotics typically are given after a dose of NMBA, this interaction needs to be considered when re-dosing NMBA.<sup id="cite_ref-Uptodate_12-25" class="reference"><a href="#cite_note-Uptodate-12"><span class="cite-bracket">[</span>12<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading3"><h3 id="Anti-seizure_drugs">Anti-seizure drugs</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Neuromuscular-blocking_drug&action=edit&section=23" title="Edit section: Anti-seizure drugs"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>Patients receiving chronic treatment are relatively resistance to nondepolarising NMBAs due to the accelerated <a href="/wiki/Clearance_(pharmacology)" title="Clearance (pharmacology)">clearance</a>.<sup id="cite_ref-Uptodate_12-26" class="reference"><a href="#cite_note-Uptodate-12"><span class="cite-bracket">[</span>12<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading3"><h3 id="Lithium">Lithium</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Neuromuscular-blocking_drug&action=edit&section=24" title="Edit section: Lithium"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>Lithium is structurally similar to other cations such as sodium, potassium, magnesium and calcium, this causes lithium to activate potassium channels which inhibit neuromuscular transmission.<sup id="cite_ref-Uptodate_12-27" class="reference"><a href="#cite_note-Uptodate-12"><span class="cite-bracket">[</span>12<span class="cite-bracket">]</span></a></sup> Patients who take lithium can have a prolonged response to both depolarising and nondepolarising NMBAs. </p> <div class="mw-heading mw-heading3"><h3 id="Antidepressants">Antidepressants</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Neuromuscular-blocking_drug&action=edit&section=25" title="Edit section: Antidepressants"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p><a href="/wiki/Sertraline" title="Sertraline">Sertraline</a> and <a href="/wiki/Amitriptyline" title="Amitriptyline">amitriptyline</a> inhibit <a href="/wiki/Butyrylcholinesterase" title="Butyrylcholinesterase">butyrylcholinesterase</a> and cause prolonged <a href="/wiki/Paralysis" title="Paralysis">paralysis</a>.<sup id="cite_ref-Uptodate_12-28" class="reference"><a href="#cite_note-Uptodate-12"><span class="cite-bracket">[</span>12<span class="cite-bracket">]</span></a></sup> Mivacurium causes prolonged paralysis for patients chronically taking sertraline.<sup id="cite_ref-Uptodate_12-29" class="reference"><a href="#cite_note-Uptodate-12"><span class="cite-bracket">[</span>12<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading3"><h3 id="Local_anesthetics_(LAs)"><span id="Local_anesthetics_.28LAs.29"></span>Local anesthetics (LAs)</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Neuromuscular-blocking_drug&action=edit&section=26" title="Edit section: Local anesthetics (LAs)"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p><a href="/wiki/Local_anesthetic" title="Local anesthetic">LAs</a> may enhance the effects of depolarisation and nondepolarising NMBAs through pre and post-synaptic interactions at the NMJ.<sup id="cite_ref-Uptodate_12-30" class="reference"><a href="#cite_note-Uptodate-12"><span class="cite-bracket">[</span>12<span class="cite-bracket">]</span></a></sup> It may result in blood levels high enough to potentiate NMBA-induced neuromuscular block.<sup id="cite_ref-Uptodate_12-31" class="reference"><a href="#cite_note-Uptodate-12"><span class="cite-bracket">[</span>12<span class="cite-bracket">]</span></a></sup> Epidurally administered <a href="/wiki/Levobupivacaine" title="Levobupivacaine">levobupivacaine</a> and <a href="/wiki/Mepivacaine" title="Mepivacaine">mepivacaine</a> potentiate <a href="/wiki/Aminosteroid" title="Aminosteroid">amino-steroidal NMBAs</a> and delay recovery from neuromuscular blockade.<sup id="cite_ref-Uptodate_12-32" class="reference"><a href="#cite_note-Uptodate-12"><span class="cite-bracket">[</span>12<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading2"><h2 id="Estimating_effect">Estimating effect</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Neuromuscular-blocking_drug&action=edit&section=27" title="Edit section: Estimating effect"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>Methods for estimating the degree of neuromuscular block include valuation of muscular response to stimuli from surface electrodes, such as in the <i><a href="/wiki/Neuromuscular_monitoring" title="Neuromuscular monitoring">train-of-four</a></i> test, wherein four such stimuli are given in rapid succession. With no neuromuscular blockade, the resultant muscle contractions are of equal strength, but gradually decrease in case of neuromuscular blockade.<sup id="cite_ref-27" class="reference"><a href="#cite_note-27"><span class="cite-bracket">[</span>27<span class="cite-bracket">]</span></a></sup> It is recommended during use of continuous-infusion neuromuscular blocking agents in <a href="/wiki/Intensive_care" class="mw-redirect" title="Intensive care">intensive care</a>.<sup id="cite_ref-28" class="reference"><a href="#cite_note-28"><span class="cite-bracket">[</span>28<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading2"><h2 id="Reversal">Reversal</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Neuromuscular-blocking_drug&action=edit&section=28" title="Edit section: Reversal"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>The effect of non-depolarizing neuromuscular-blocking drugs may be reversed with <a href="/wiki/Acetylcholinesterase_inhibitor" title="Acetylcholinesterase inhibitor">acetylcholinesterase inhibitors</a>, <a href="/wiki/Neostigmine" title="Neostigmine">neostigmine</a>, and <a href="/wiki/Edrophonium" title="Edrophonium">edrophonium</a>, as commonly used examples. Of these, edrophonium has a faster onset of action than neostigmine, but it is unreliable when used to antagonize deep neuromuscular block.<sup id="cite_ref-29" class="reference"><a href="#cite_note-29"><span class="cite-bracket">[</span>29<span class="cite-bracket">]</span></a></sup> Acetylcholinesterase inhibitors increase the amount of acetylcholine in the neuromuscular junction, so a prerequisite for their effect is that the neuromuscular block is not complete, because in case every acetylcholine receptor is blocked then it does not matter how much acetylcholine is present. </p><p><a href="/wiki/Sugammadex" title="Sugammadex">Sugammadex</a> is a newer drug for reversing neuromuscular block by <a href="/wiki/Rocuronium" class="mw-redirect" title="Rocuronium">rocuronium</a> and vecuronium in <a href="/wiki/General_anaesthesia" title="General anaesthesia">general anaesthesia</a>. It is the first <a href="/wiki/Selective_relaxant_binding_agent" class="mw-redirect" title="Selective relaxant binding agent">selective relaxant binding agent</a> (SRBA).<sup id="cite_ref-30" class="reference"><a href="#cite_note-30"><span class="cite-bracket">[</span>30<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading2"><h2 id="History">History</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Neuromuscular-blocking_drug&action=edit&section=29" title="Edit section: History"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p><a href="/wiki/Curare" title="Curare">Curare</a> is a crude <a href="/wiki/Extract" title="Extract">extract</a> from certain South American plants in the genera <i><a href="/wiki/Strychnos" title="Strychnos">Strychnos</a></i> and <i><a href="/wiki/Chondrodendron" title="Chondrodendron">Chondrodendron</a></i>, originally brought to Europe by explorers such as <a href="/wiki/Walter_Raleigh" title="Walter Raleigh">Walter Raleigh</a><sup id="cite_ref-31" class="reference"><a href="#cite_note-31"><span class="cite-bracket">[</span>31<span class="cite-bracket">]</span></a></sup> <a href="/wiki/Edward_Bancroft" title="Edward Bancroft">Edward Bancroft</a>, a chemist and physician in the 16th century brought samples of crude curare from <a href="/wiki/South_America" title="South America">South America</a> back to the Old-World. The effect of curare was experimented with by <a href="/wiki/Sir_Benjamin_Collins_Brodie,_1st_Baronet" title="Sir Benjamin Collins Brodie, 1st Baronet">Sir Benjamin Brodie</a> when he injected small animals with <a href="/wiki/Curare" title="Curare">curare</a>, and found that the animals stopped breathing but could be kept alive by inflating their lungs with <a href="/wiki/Bellows" title="Bellows">bellows</a>. This observation led to the conclusion that curare can paralyse the respiratory muscles. It was also experimented by <a href="/wiki/Charles_Waterton" title="Charles Waterton">Charles Waterton</a> in 1814 when he injected three donkeys with curare. The first donkey was injected in the shoulder and died afterward. The second donkey had a <a href="/wiki/Tourniquet" title="Tourniquet">tourniquet</a> applied to the foreleg and was injected distal to the tourniquet. The donkey lived while the tourniquet was in place but died after it was removed. The third donkey after injected with curare appeared to be dead but was resuscitated using bellows. Charles Waterton's experiment confirmed the paralytic effect of curare. </p><p>It was known in the 19th century to have a <a href="/wiki/Paralysis" title="Paralysis">paralysing effect</a>, due in part to the studies of scientists like <a href="/wiki/Claude_Bernard" title="Claude Bernard">Claude Bernard</a>.<sup id="cite_ref-32" class="reference"><a href="#cite_note-32"><span class="cite-bracket">[</span>32<span class="cite-bracket">]</span></a></sup> <a href="/wiki/Tubocurarine" class="mw-redirect" title="Tubocurarine">D-tubocurarine</a> a <i>mono</i>-quaternary <a href="/wiki/Alkaloid" title="Alkaloid">alkaloid</a> was isolated from <i><a href="/wiki/Chondrodendron_tomentosum" title="Chondrodendron tomentosum">Chondrodendron tomentosum</a></i> in 1942, and it was shown to be the major constituent in curare responsible for producing the paralysing effect. At that time, it was known that curare and, therefore, d-tubocurarine worked at the <a href="/wiki/Neuromuscular_junction" title="Neuromuscular junction">neuromuscular junction</a>. The isolation of tubocurarine and its marketing as the drug <a href="/wiki/Intocostrin" class="mw-redirect" title="Intocostrin">Intocostrin</a> led to more research in the field of neuromuscular-blocking drugs. Scientists figured out that the potency of tubocurarine was related to the separation distance between the two <a href="/wiki/Quaternary_ammonium" class="mw-redirect" title="Quaternary ammonium">quaternary ammonium</a> heads.<sup id="cite_ref-T._Raghavendra_2002_9-1" class="reference"><a href="#cite_note-T._Raghavendra_2002-9"><span class="cite-bracket">[</span>9<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-O.A.Nedergard_2003_33-0" class="reference"><a href="#cite_note-O.A.Nedergard_2003-33"><span class="cite-bracket">[</span>33<span class="cite-bracket">]</span></a></sup> </p><p>Neurologist <a href="/wiki/Walter_Jackson_Freeman_II" title="Walter Jackson Freeman II">Walter Freeman</a> learned about curare and suggested to <a href="/wiki/Richard_Gill_(plant_collector)" title="Richard Gill (plant collector)">Richard Gill</a>, a patient suffering from <a href="/wiki/Multiple_sclerosis" title="Multiple sclerosis">multiple sclerosis</a>, that he try using it. Gill brought 25 pounds of raw curare from Ecuador. The raw curare was then given to <a href="/wiki/Bristol-Myers_Squibb" class="mw-redirect" title="Bristol-Myers Squibb">Squibb and Sons</a> to derive an effective antidote to curare. In 1942, Wintersteiner and Dutcher (two scientists working for Squibb and Sons) isolated the alkaloid <a href="/wiki/D-tubocurarine" class="mw-redirect" title="D-tubocurarine">d-tubocurarine</a>. Soon after, they developed a preparation of curare called <a href="/wiki/Intocostrin" class="mw-redirect" title="Intocostrin">Intocostrin</a>. </p><p>At the same time in Montreal, <a href="/wiki/Harold_Randall_Griffith" class="mw-redirect" title="Harold Randall Griffith">Harold Randall Griffith</a> and his resident Enid Johnson at the Homeopathic Hospital administered curare to a young patient undergoing <a href="/wiki/Appendectomy" title="Appendectomy">appendectomy</a>. This was the first use of NMBA as muscle relaxant in anesthesia. </p><p>The 1940s, 1950s and 1960s saw the rapid development of several synthetic NMBA. <a href="/wiki/Gallamine" class="mw-redirect" title="Gallamine">Gallamine</a> was the first synthetic NMBA used clinically. Further research led to the development of <a href="/wiki/Chemical_synthesis" title="Chemical synthesis">synthesized</a> molecules with different curariform effects, depending on the distance between the <a href="/wiki/Quaternary_ammonium" class="mw-redirect" title="Quaternary ammonium">quaternary ammonium</a> groups. One of the synthesized <i>bis</i>-quaternaries was <a href="/wiki/Decamethonium" title="Decamethonium">decamethonium</a> a 10-<a href="/wiki/Carbon" title="Carbon">carbon</a> <i>bis</i>-quaternary compound. Following research with decamethonium, scientists developed <a href="/wiki/Suxamethonium" class="mw-redirect" title="Suxamethonium">suxamethonium</a>, which is a double acetylcholine molecule that was connected at the <a href="/wiki/Acetyl" class="mw-redirect" title="Acetyl">acetyl</a> end. The discovery and development of suxamethonium lead to a <a href="/wiki/Nobel_Prize_in_medicine" class="mw-redirect" title="Nobel Prize in medicine">Nobel Prize in medicine</a> in 1957. Suxamethonium showed different blocking effect in that its effect was achieved more quickly and augmented a response in the <a href="/wiki/Muscle" title="Muscle">muscle</a> before block. Also, tubocurarine effects were known to be reversible by <a href="/wiki/Acetylcholinesterase_inhibitor" title="Acetylcholinesterase inhibitor">acetylcholinesterase inhibitors</a>, whereas decamethonium and suxamethonium block were not reversible.<sup id="cite_ref-T._Raghavendra_2002_9-2" class="reference"><a href="#cite_note-T._Raghavendra_2002-9"><span class="cite-bracket">[</span>9<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-Bowman_2006_5-7" class="reference"><a href="#cite_note-Bowman_2006-5"><span class="cite-bracket">[</span>5<span class="cite-bracket">]</span></a></sup> </p><p>Another compound <a href="/w/index.php?title=Malou%C3%A9tine&action=edit&redlink=1" class="new" title="Malouétine (page does not exist)">malouétine</a> that was a <i>bis</i>-quaternary steroid was isolated from the plant <i><a href="/w/index.php?title=Malouetia_bequaertiana&action=edit&redlink=1" class="new" title="Malouetia bequaertiana (page does not exist)">Malouetia bequaertiana</a></i> and showed curariform activity. This led to the synthetic drug <a href="/wiki/Pancuronium" class="mw-redirect" title="Pancuronium">pancuronium</a>, a <i>bis</i>-quaternary steroid, and subsequently other drugs that had better pharmacological properties.<sup id="cite_ref-T._Raghavendra_2002_9-3" class="reference"><a href="#cite_note-T._Raghavendra_2002-9"><span class="cite-bracket">[</span>9<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-A._G._McKenzie_2000_34-0" class="reference"><a href="#cite_note-A._G._McKenzie_2000-34"><span class="cite-bracket">[</span>34<span class="cite-bracket">]</span></a></sup> Research on these molecules helped improve understanding of the <a href="/wiki/Physiology" title="Physiology">physiology</a> of <a href="/wiki/Neurons" class="mw-redirect" title="Neurons">neurons</a> and <a href="/wiki/Receptor_(biochemistry)" title="Receptor (biochemistry)">receptors</a>. </p> <div class="mw-heading mw-heading3"><h3 id="Outdated_treatment">Outdated treatment</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Neuromuscular-blocking_drug&action=edit&section=30" title="Edit section: Outdated treatment"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p><a href="/wiki/Gallamine_triethiodide" title="Gallamine triethiodide">Gallamine triethiodide</a> is originally developed for preventing muscle contractions during surgical procedures. However, it is no longer marketed in the United States according to the <a href="/wiki/FDA_orange_book" class="mw-redirect" title="FDA orange book">FDA orange book</a>. </p> <div class="mw-heading mw-heading2"><h2 id="See_also">See also</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Neuromuscular-blocking_drug&action=edit&section=31" title="Edit section: See also"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <ul><li><a href="/wiki/Ganglionic_blocker" title="Ganglionic blocker">Ganglionic blocker</a></li> <li><a href="/wiki/Cholinergic_blocking_drugs" class="mw-redirect" title="Cholinergic blocking drugs">Cholinergic blocking drugs</a></li></ul> <div class="mw-heading mw-heading2"><h2 id="References">References</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Neuromuscular-blocking_drug&action=edit&section=32" title="Edit section: References"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <style data-mw-deduplicate="TemplateStyles:r1239543626">.mw-parser-output .reflist{margin-bottom:0.5em;list-style-type:decimal}@media screen{.mw-parser-output .reflist{font-size:90%}}.mw-parser-output .reflist .references{font-size:100%;margin-bottom:0;list-style-type:inherit}.mw-parser-output .reflist-columns-2{column-width:30em}.mw-parser-output .reflist-columns-3{column-width:25em}.mw-parser-output .reflist-columns{margin-top:0.3em}.mw-parser-output .reflist-columns ol{margin-top:0}.mw-parser-output .reflist-columns li{page-break-inside:avoid;break-inside:avoid-column}.mw-parser-output .reflist-upper-alpha{list-style-type:upper-alpha}.mw-parser-output .reflist-upper-roman{list-style-type:upper-roman}.mw-parser-output .reflist-lower-alpha{list-style-type:lower-alpha}.mw-parser-output .reflist-lower-greek{list-style-type:lower-greek}.mw-parser-output .reflist-lower-roman{list-style-type:lower-roman}</style><div class="reflist reflist-columns references-column-width" style="column-width: 30em;"> <ol class="references"> <li id="cite_note-urlDorlands_Medical_Dictionary:neuromuscular_blocking_agent-1"><span class="mw-cite-backlink"><b><a href="#cite_ref-urlDorlands_Medical_Dictionary:neuromuscular_blocking_agent_1-0">^</a></b></span> <span class="reference-text"><style data-mw-deduplicate="TemplateStyles:r1238218222">.mw-parser-output cite.citation{font-style:inherit;word-wrap:break-word}.mw-parser-output .citation q{quotes:"\"""\"""'""'"}.mw-parser-output .citation:target{background-color:rgba(0,127,255,0.133)}.mw-parser-output .id-lock-free.id-lock-free a{background:url("//upload.wikimedia.org/wikipedia/commons/6/65/Lock-green.svg")right 0.1em center/9px no-repeat}.mw-parser-output .id-lock-limited.id-lock-limited a,.mw-parser-output .id-lock-registration.id-lock-registration a{background:url("//upload.wikimedia.org/wikipedia/commons/d/d6/Lock-gray-alt-2.svg")right 0.1em center/9px no-repeat}.mw-parser-output .id-lock-subscription.id-lock-subscription a{background:url("//upload.wikimedia.org/wikipedia/commons/a/aa/Lock-red-alt-2.svg")right 0.1em center/9px no-repeat}.mw-parser-output .cs1-ws-icon a{background:url("//upload.wikimedia.org/wikipedia/commons/4/4c/Wikisource-logo.svg")right 0.1em center/12px no-repeat}body:not(.skin-timeless):not(.skin-minerva) .mw-parser-output .id-lock-free a,body:not(.skin-timeless):not(.skin-minerva) .mw-parser-output .id-lock-limited a,body:not(.skin-timeless):not(.skin-minerva) .mw-parser-output .id-lock-registration a,body:not(.skin-timeless):not(.skin-minerva) .mw-parser-output .id-lock-subscription a,body:not(.skin-timeless):not(.skin-minerva) .mw-parser-output .cs1-ws-icon a{background-size:contain;padding:0 1em 0 0}.mw-parser-output .cs1-code{color:inherit;background:inherit;border:none;padding:inherit}.mw-parser-output .cs1-hidden-error{display:none;color:var(--color-error,#d33)}.mw-parser-output .cs1-visible-error{color:var(--color-error,#d33)}.mw-parser-output .cs1-maint{display:none;color:#085;margin-left:0.3em}.mw-parser-output .cs1-kern-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right{padding-right:0.2em}.mw-parser-output .citation .mw-selflink{font-weight:inherit}@media screen{.mw-parser-output .cs1-format{font-size:95%}html.skin-theme-clientpref-night .mw-parser-output .cs1-maint{color:#18911f}}@media screen and (prefers-color-scheme:dark){html.skin-theme-clientpref-os .mw-parser-output .cs1-maint{color:#18911f}}</style><cite class="citation web cs1"><a rel="nofollow" class="external text" href="http://www.mercksource.com/pp/us/cns/cns_hl_dorlands_split.jsp?pg=/ppdocs/us/common/dorlands/dorland/one/000002250.htm">"Dorlands Medical Dictionary:neuromuscular blocking agent"</a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=unknown&rft.btitle=Dorlands+Medical+Dictionary%3Aneuromuscular+blocking+agent&rft_id=http%3A%2F%2Fwww.mercksource.com%2Fpp%2Fus%2Fcns%2Fcns_hl_dorlands_split.jsp%3Fpg%3D%2Fppdocs%2Fus%2Fcommon%2Fdorlands%2Fdorland%2Fone%2F000002250.htm&rfr_id=info%3Asid%2Fen.wikipedia.org%3ANeuromuscular-blocking+drug" class="Z3988"></span><sup class="noprint Inline-Template"><span style="white-space: nowrap;">[<i><a href="/wiki/Wikipedia:Link_rot" title="Wikipedia:Link rot"><span title=" Dead link tagged April 2020">permanent dead link</span></a></i><span style="visibility:hidden; color:transparent; padding-left:2px">‍</span>]</span></sup></span> </li> <li id="cite_note-2"><span class="mw-cite-backlink"><b><a href="#cite_ref-2">^</a></b></span> <span class="reference-text">Jahromi, Behdad, Knezevic, Nebojsa & Nick MD, PhD. (2020). Neuromuscular Block Monitoring in Patients With Facial Rejuvenation: A Case Report. <i>A&A Practice</i>, <i>14</i>, e01334. <link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<a rel="nofollow" class="external text" href="https://doi.org/10.1213%2FXAA.0000000000001334">10.1213/XAA.0000000000001334</a></span> </li> <li id="cite_note-3"><span class="mw-cite-backlink"><b><a href="#cite_ref-3">^</a></b></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFJahromiKnezevic2020" class="citation journal cs1">Jahromi B, Knezevic NN (November 2020). 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title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=Surgical+Endoscopy&rft.atitle=Neuromuscular+blockade+improves+surgical+conditions+%28NISCO%29&rft.volume=29&rft.issue=3&rft.pages=627-36&rft.date=2015-03&rft_id=info%3Adoi%2F10.1007%2Fs00464-014-3711-7&rft_id=info%3Apmid%2F25125097&rft.aulast=Blobner&rft.aufirst=M&rft.au=Frick%2C+CG&rft.au=St%C3%A4uble%2C+RB&rft.au=Feussner%2C+H&rft.au=Schaller%2C+SJ&rft.au=Unterbuchner%2C+C&rft.au=Lingg%2C+C&rft.au=Geisler%2C+M&rft.au=Fink%2C+H&rfr_id=info%3Asid%2Fen.wikipedia.org%3ANeuromuscular-blocking+drug" class="Z3988"></span></span> </li> <li id="cite_note-Bowman_2006-5"><span class="mw-cite-backlink">^ <a href="#cite_ref-Bowman_2006_5-0"><sup><i><b>a</b></i></sup></a> <a href="#cite_ref-Bowman_2006_5-1"><sup><i><b>b</b></i></sup></a> <a href="#cite_ref-Bowman_2006_5-2"><sup><i><b>c</b></i></sup></a> <a href="#cite_ref-Bowman_2006_5-3"><sup><i><b>d</b></i></sup></a> <a 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id="cite_note-Lee_2001-6"><span class="mw-cite-backlink">^ <a href="#cite_ref-Lee_2001_6-0"><sup><i><b>a</b></i></sup></a> <a href="#cite_ref-Lee_2001_6-1"><sup><i><b>b</b></i></sup></a> <a href="#cite_ref-Lee_2001_6-2"><sup><i><b>c</b></i></sup></a> <a href="#cite_ref-Lee_2001_6-3"><sup><i><b>d</b></i></sup></a> <a href="#cite_ref-Lee_2001_6-4"><sup><i><b>e</b></i></sup></a></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFLee2001" class="citation journal cs1">Lee C (November 2001). <a rel="nofollow" class="external text" href="https://doi.org/10.1093%2Fbja%2F87.5.755">"Structure, conformation, and action of neuromuscular blocking drugs"</a>. <i>British Journal of Anaesthesia</i>. <b>87</b> (5): 755–769. <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<span class="id-lock-free" title="Freely accessible"><a rel="nofollow" class="external text" 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href="https://meshb.nlm.nih.gov/record/ui?name=Neuromuscular+Nondepolarizing+Agents">Neuromuscular+Nondepolarizing+Agents</a> at the U.S. National Library of Medicine <a href="/wiki/Medical_Subject_Headings" title="Medical Subject Headings">Medical Subject Headings</a> (MeSH)</span> </li> <li id="cite_note-T._Raghavendra_2002-9"><span class="mw-cite-backlink">^ <a href="#cite_ref-T._Raghavendra_2002_9-0"><sup><i><b>a</b></i></sup></a> <a href="#cite_ref-T._Raghavendra_2002_9-1"><sup><i><b>b</b></i></sup></a> <a href="#cite_ref-T._Raghavendra_2002_9-2"><sup><i><b>c</b></i></sup></a> <a href="#cite_ref-T._Raghavendra_2002_9-3"><sup><i><b>d</b></i></sup></a></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFRaghavendra2002" class="citation journal cs1">Raghavendra T (July 2002). <a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1279945">"Neuromuscular blocking 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(1990). <i>Goodman and Gilman's The Pharmacological Basis of Therapeutics</i>, 8th ed. A. G. Gilman et al. (eds.). New York: Pergamon Press. p. 167. <link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><a href="/wiki/ISBN_(identifier)" class="mw-redirect" title="ISBN (identifier)">ISBN</a> <a href="/wiki/Special:BookSources/0071052704" title="Special:BookSources/0071052704">0071052704</a>.</span> </li> <li id="cite_note-32"><span class="mw-cite-backlink"><b><a href="#cite_ref-32">^</a></b></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFBernard1857" class="citation book cs1 cs1-prop-foreign-lang-source"><a href="/wiki/Claude_Bernard" title="Claude Bernard">Bernard C</a> (1857). <a rel="nofollow" class="external text" href="https://archive.org/stream/leonssurlesef00bern#page/369/mode/1up">"25th lesson"</a>. <i>Leçons sur les effets des substances toxiques et médicamenteuses</i> (in French). Paris: J.B. Baillière. pp. 369–80.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.atitle=25th+lesson&rft.btitle=Le%C3%A7ons+sur+les+effets+des+substances+toxiques+et+m%C3%A9dicamenteuses&rft.place=Paris&rft.pages=369-80&rft.pub=J.B.+Bailli%C3%A8re&rft.date=1857&rft.aulast=Bernard&rft.aufirst=C&rft_id=https%3A%2F%2Farchive.org%2Fstream%2Fleonssurlesef00bern%23page%2F369%2Fmode%2F1up&rfr_id=info%3Asid%2Fen.wikipedia.org%3ANeuromuscular-blocking+drug" class="Z3988"></span></span> </li> <li id="cite_note-O.A.Nedergard_2003-33"><span class="mw-cite-backlink"><b><a href="#cite_ref-O.A.Nedergard_2003_33-0">^</a></b></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFNedergaard2003" class="citation journal cs1">Nedergaard OA (April 2003). <a rel="nofollow" class="external text" href="https://doi.org/10.1034%2Fj.1600-0773.2003.920402.x">"Curare: the flying death"</a>. <i>Pharmacology & Toxicology</i>. <b>92</b> (4): 154–155. <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<span class="id-lock-free" title="Freely accessible"><a rel="nofollow" class="external text" href="https://doi.org/10.1034%2Fj.1600-0773.2003.920402.x">10.1034/j.1600-0773.2003.920402.x</a></span>. <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/12753415">12753415</a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=Pharmacology+%26+Toxicology&rft.atitle=Curare%3A+the+flying+death&rft.volume=92&rft.issue=4&rft.pages=154-155&rft.date=2003-04&rft_id=info%3Adoi%2F10.1034%2Fj.1600-0773.2003.920402.x&rft_id=info%3Apmid%2F12753415&rft.aulast=Nedergaard&rft.aufirst=OA&rft_id=https%3A%2F%2Fdoi.org%2F10.1034%252Fj.1600-0773.2003.920402.x&rfr_id=info%3Asid%2Fen.wikipedia.org%3ANeuromuscular-blocking+drug" class="Z3988"></span></span> </li> <li id="cite_note-A._G._McKenzie_2000-34"><span class="mw-cite-backlink"><b><a href="#cite_ref-A._G._McKenzie_2000_34-0">^</a></b></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFMcKenzie2000" class="citation journal cs1">McKenzie AG (June 2000). "Prelude to pancuronium and vecuronium". <i>Anaesthesia</i>. <b>55</b> (6): 551–556. <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<a rel="nofollow" class="external text" href="https://doi.org/10.1046%2Fj.1365-2044.2000.01423.x">10.1046/j.1365-2044.2000.01423.x</a>. <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/10866718">10866718</a>. <a href="/wiki/S2CID_(identifier)" class="mw-redirect" title="S2CID (identifier)">S2CID</a> <a rel="nofollow" class="external text" href="https://api.semanticscholar.org/CorpusID:22476701">22476701</a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=Anaesthesia&rft.atitle=Prelude+to+pancuronium+and+vecuronium&rft.volume=55&rft.issue=6&rft.pages=551-556&rft.date=2000-06&rft_id=https%3A%2F%2Fapi.semanticscholar.org%2FCorpusID%3A22476701%23id-name%3DS2CID&rft_id=info%3Apmid%2F10866718&rft_id=info%3Adoi%2F10.1046%2Fj.1365-2044.2000.01423.x&rft.aulast=McKenzie&rft.aufirst=AG&rfr_id=info%3Asid%2Fen.wikipedia.org%3ANeuromuscular-blocking+drug" class="Z3988"></span></span> </li> </ol></div> <div class="mw-heading mw-heading2"><h2 id="External_links">External links</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Neuromuscular-blocking_drug&action=edit&section=33" title="Edit section: External links"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <ul><li><a rel="nofollow" class="external text" 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abbr{font-variant:small-caps;border-bottom:none;text-decoration:none;cursor:inherit}.mw-parser-output .navbar-ct-full{font-size:114%;margin:0 7em}.mw-parser-output .navbar-ct-mini{font-size:114%;margin:0 4em}html.skin-theme-clientpref-night .mw-parser-output .navbar li a abbr{color:var(--color-base)!important}@media(prefers-color-scheme:dark){html.skin-theme-clientpref-os .mw-parser-output .navbar li a abbr{color:var(--color-base)!important}}@media print{.mw-parser-output .navbar{display:none!important}}</style><div class="navbar plainlinks hlist navbar-mini"><ul><li class="nv-view"><a href="/wiki/Template:Pharmacomodulation" title="Template:Pharmacomodulation"><abbr title="View this template">v</abbr></a></li><li class="nv-talk"><a href="/wiki/Template_talk:Pharmacomodulation" title="Template talk:Pharmacomodulation"><abbr title="Discuss this template">t</abbr></a></li><li class="nv-edit"><a href="/wiki/Special:EditPage/Template:Pharmacomodulation" title="Special:EditPage/Template:Pharmacomodulation"><abbr title="Edit this template">e</abbr></a></li></ul></div><div id="Pharmacomodulation" style="font-size:114%;margin:0 4em"><a href="/wiki/Pharmacology" title="Pharmacology">Pharmacomodulation</a></div></th></tr><tr><th scope="row" class="navbox-group" style="width:1%">Types</th><td class="navbox-list-with-group navbox-list navbox-odd hlist" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li>♦ <a href="/wiki/Enzyme" title="Enzyme">Enzyme</a>: <a href="/wiki/Enzyme_inducer" title="Enzyme inducer">Inducer</a></li> <li><a href="/wiki/Enzyme_inhibitor" title="Enzyme inhibitor">Inhibitor</a></li></ul> <ul><li>♦ <a href="/wiki/Ion_channel" title="Ion channel">Ion channel</a>: <a href="/wiki/Channel_opener" title="Channel opener">Opener</a></li> <li><a href="/wiki/Channel_blocker" title="Channel blocker">Blocker</a></li></ul> <ul><li>♦ <a href="/wiki/Receptor_(biochemistry)" title="Receptor (biochemistry)">Receptor</a>: <a href="/wiki/Agonist" title="Agonist">Agonist</a></li> <li><a href="/wiki/Partial_agonist" title="Partial agonist">Partial agonist</a></li> <li><a href="/wiki/Receptor_antagonist" title="Receptor antagonist">Antagonist</a></li> <li><a href="/wiki/Inverse_agonist" title="Inverse agonist">Inverse agonist</a></li> <li><a href="/wiki/Positive_allosteric_modulator" class="mw-redirect" title="Positive allosteric modulator">Positive allosteric modulator</a> (PAM)</li> <li><a href="/wiki/Negative_allosteric_modulator" class="mw-redirect" title="Negative allosteric modulator">Negative allosteric modulator</a> (NAM)</li></ul> <ul><li>♦ <a href="/wiki/Membrane_transport_protein" title="Membrane transport protein">Transporter</a> [<a href="/wiki/Reuptake" title="Reuptake">Reuptake</a> vs <a href="/wiki/Reverse_transport" title="Reverse transport">Efflux</a>]: <a href="/wiki/Reuptake_enhancer" title="Reuptake enhancer">Enhancer</a> (RE)</li> <li><a href="/wiki/Reuptake_inhibitor" title="Reuptake inhibitor">Inhibitor</a> (RI)</li> <li><a href="/wiki/Releasing_agent" class="mw-redirect" title="Releasing agent">Releaser</a> (RA)</li></ul> <ul><li>♦ Miscellaneous: <a href="/wiki/Precursor_(chemistry)" title="Precursor (chemistry)">Precursor</a></li> <li><a href="/wiki/Cofactor_(biochemistry)" title="Cofactor (biochemistry)">Cofactor</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%">Classes</th><td class="navbox-list-with-group navbox-list navbox-odd hlist" style="width:100%;padding:0"><div style="padding:0 0.25em"></div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Enzyme" title="Enzyme">Enzyme</a></th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em">see <i><a href="/wiki/Template:Enzyme_inhibition" title="Template:Enzyme inhibition">Enzyme inhibition</a></i></div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Ion_channel" title="Ion channel">Ion channel</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em">See <a href="/wiki/Template:Channel_blockers" class="mw-redirect" title="Template:Channel blockers">Ion channel modulators</a></div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Receptor_(biochemistry)" title="Receptor (biochemistry)">Receptor</a> &<br /><a href="/wiki/Membrane_transport_protein" title="Membrane transport protein">transporter</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"></div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Biogenic_amine" title="Biogenic amine">BA</a>/<a href="/wiki/Monoamine_neurotransmitter" title="Monoamine neurotransmitter">M</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"></div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><th id="Adrenergic" scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Adrenergic" title="Adrenergic">Adrenergic</a></th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Adrenergic_agonist" title="Adrenergic agonist">Adrenergic receptor agonist</a> (<a href="/wiki/Alpha-adrenergic_agonist" title="Alpha-adrenergic agonist">α</a></li> <li><a href="/wiki/Beta-adrenergic_agonist" title="Beta-adrenergic agonist">β</a> (<a href="/wiki/Beta1-adrenergic_agonist" title="Beta1-adrenergic agonist">1</a></li> <li><a href="/wiki/Beta2-adrenergic_agonist" title="Beta2-adrenergic agonist">2</a>))</li> <li><a href="/wiki/Adrenergic_antagonist" title="Adrenergic antagonist">Adrenergic receptor antagonist</a> (<a href="/wiki/Alpha_blocker" title="Alpha blocker">α</a> (<a href="/wiki/Alpha-1_blocker" title="Alpha-1 blocker">1</a></li> <li><a href="/wiki/Alpha-2_blocker" title="Alpha-2 blocker">2</a>)</li> <li><a href="/wiki/Beta_blocker" title="Beta blocker">β</a>)</li> <li><a href="/wiki/Norepinephrine_reuptake_inhibitor" title="Norepinephrine reuptake inhibitor">Norepinephrine reuptake inhibitor</a> (NRI)</li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Dopaminergic" title="Dopaminergic">Dopaminergic</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Dopamine_agonist" title="Dopamine agonist">Dopamine receptor agonist</a></li> <li><a href="/wiki/Dopamine_antagonist" title="Dopamine antagonist">Dopamine receptor antagonist</a></li> <li><a href="/wiki/Dopamine_reuptake_inhibitor" title="Dopamine reuptake inhibitor">Dopamine reuptake inhibitor</a> (DRI)</li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Histaminergic" title="Histaminergic">Histaminergic</a></th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Histamine_agonist" title="Histamine agonist">Histamine receptor agonist</a></li> <li><a href="/wiki/Histamine_antagonist" class="mw-redirect" title="Histamine antagonist">Histamine receptor antagonist</a> (<a href="/wiki/H1_antagonist" title="H1 antagonist">H<sub>1</sub></a></li> <li><a href="/wiki/H2_antagonist" class="mw-redirect" title="H2 antagonist">H<sub>2</sub></a></li> <li><a href="/wiki/H3_receptor_antagonist" title="H3 receptor antagonist">H<sub>3</sub></a>)</li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Serotonin" title="Serotonin">Serotonergic</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Serotonin_receptor_agonist" title="Serotonin receptor agonist">Serotonin receptor agonist</a></li> <li><a href="/wiki/Serotonin_antagonist" class="mw-redirect" title="Serotonin antagonist">Serotonin receptor antagonist</a> (<a href="/wiki/5-HT3_antagonist" title="5-HT3 antagonist">5-HT<sub>3</sub></a>)</li> <li><a href="/wiki/Serotonin_reuptake_inhibitor" title="Serotonin reuptake inhibitor">Serotonin reuptake inhibitor</a> (SRI)</li></ul> </div></td></tr></tbody></table><div></div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Amino_acid" title="Amino acid">AA</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"></div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/GABAergic" title="GABAergic">GABAergic</a></th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/GABA_agonist" class="mw-redirect" title="GABA agonist">GABA receptor agonist</a></li> <li><a href="/wiki/GABA_antagonist" class="mw-redirect" title="GABA antagonist">GABA receptor antagonist</a></li> <li><a href="/wiki/GABA_reuptake_inhibitor" title="GABA reuptake inhibitor">GABA reuptake inhibitor</a> (GRI)</li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Glutamatergic" title="Glutamatergic">Glutamatergic</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Excitatory_amino_acid_agonist" class="mw-redirect" title="Excitatory amino acid agonist">Glutamate receptor agonist</a> (<a href="/wiki/Ampakine" title="Ampakine">AMPA</a>)</li> <li><a href="/wiki/Excitatory_amino_acid_antagonist" class="mw-redirect" title="Excitatory amino acid antagonist">Glutamate receptor antagonist</a> (<a href="/wiki/NMDA_receptor_antagonist" title="NMDA receptor antagonist">NMDA</a>)</li> <li><a href="/wiki/Excitatory_amino_acid_reuptake_inhibitor" title="Excitatory amino acid reuptake inhibitor">Glutamate reuptake inhibitor</a></li></ul> </div></td></tr></tbody></table><div></div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Cholinergic" title="Cholinergic">Cholinergic</a></th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Parasympathomimetic_drug" title="Parasympathomimetic drug">Acetylcholine receptor agonist</a> (<a href="/wiki/Muscarinic_agonist" title="Muscarinic agonist">Muscarinic</a></li> <li><a href="/wiki/Nicotinic_agonist" title="Nicotinic agonist">Nicotinic</a>) <ul><li><a href="/wiki/Cholinesterase_inhibitor" title="Cholinesterase inhibitor">Cholinesterase inhibitor</a></li></ul></li> <li><a href="/wiki/Anticholinergic" title="Anticholinergic">Acetylcholine receptor antagonist</a> (<a href="/wiki/Muscarinic_antagonist" title="Muscarinic antagonist">Muscarinic</a></li> <li><a href="/wiki/Nicotinic_antagonist" title="Nicotinic antagonist">Nicotinic</a> (<a href="/wiki/Ganglionic_blocker" title="Ganglionic blocker">Ganglionic</a></li> <li><a class="mw-selflink selflink">Muscular</a>))</li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Endocannabinoid_system" title="Endocannabinoid system">Cannabinoidergic</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Cannabinoid" title="Cannabinoid">Cannabinoid receptor agonist</a></li> <li><a href="/wiki/Cannabinoid_receptor_antagonist" title="Cannabinoid receptor antagonist">Cannabinoid receptor antagonist</a></li> <li><a href="/wiki/Endocannabinoid_enhancer" title="Endocannabinoid enhancer">Endocannabinoid enhancer</a> (eCBE)</li> <li><a href="/wiki/Endocannabinoid_reuptake_inhibitor" title="Endocannabinoid reuptake inhibitor">Endocannabinoid reuptake inhibitor</a> (eCBRI)</li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Opioidergic" title="Opioidergic">Opioidergic</a></th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Opioid_modulator" title="Opioid modulator">Opioid modulator</a></li> <li><a href="/wiki/Opioid" title="Opioid">Opioid receptor agonist</a></li> <li><a href="/wiki/Opioid_antagonist" title="Opioid antagonist">Opioid receptor antagonist</a></li> <li><a href="/wiki/Enkephalinase_inhibitor" title="Enkephalinase inhibitor">Enkephalinase inhibitor</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%">Other</th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Adenosine_reuptake_inhibitor" title="Adenosine reuptake inhibitor">Adenosine reuptake inhibitor</a> (AdoRI)</li> <li><a href="/wiki/Angiotensin_II_receptor_antagonist" class="mw-redirect" title="Angiotensin II receptor antagonist">Angiotensin II receptor antagonist</a></li> <li><a href="/wiki/Endothelin_receptor_antagonist" title="Endothelin receptor antagonist">Endothelin receptor antagonist</a></li> <li><a href="/wiki/NK1_receptor_antagonist" title="NK1 receptor antagonist">NK<sub>1</sub> receptor antagonist</a></li> <li><a href="/wiki/Vasopressin_receptor_antagonist" title="Vasopressin receptor antagonist">Vasopressin receptor antagonist</a></li></ul> </div></td></tr></tbody></table><div></div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%">Miscellaneous</th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Cofactor_(biochemistry)" title="Cofactor (biochemistry)">Cofactor</a> (see <i><a href="/wiki/Template:Enzyme_cofactors" title="Template:Enzyme cofactors">Enzyme cofactors</a></i>)</li> <li><a href="/wiki/Precursor_(chemistry)" title="Precursor (chemistry)">Precursor</a> (see <i><a href="/wiki/Template:Amino_acids" class="mw-redirect" title="Template:Amino acids">Amino acids</a></i>)</li></ul> </div></td></tr></tbody></table><div></div></td></tr></tbody></table></div> <div class="navbox-styles"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1129693374"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1236075235"></div><div role="navigation" class="navbox" aria-labelledby="Skeletal_muscle_relaxants_(M03)" style="padding:3px"><table class="nowraplinks mw-collapsible autocollapse navbox-inner" style="border-spacing:0;background:transparent;color:inherit"><tbody><tr><th scope="col" class="navbox-title" colspan="2"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1129693374"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1239400231"><div class="navbar plainlinks hlist navbar-mini"><ul><li class="nv-view"><a href="/wiki/Template:Muscle_relaxants" title="Template:Muscle relaxants"><abbr title="View this template">v</abbr></a></li><li class="nv-talk"><a href="/wiki/Template_talk:Muscle_relaxants" title="Template talk:Muscle relaxants"><abbr title="Discuss this template">t</abbr></a></li><li class="nv-edit"><a href="/wiki/Special:EditPage/Template:Muscle_relaxants" title="Special:EditPage/Template:Muscle relaxants"><abbr title="Edit this template">e</abbr></a></li></ul></div><div id="Skeletal_muscle_relaxants_(M03)" style="font-size:114%;margin:0 4em">Skeletal <a href="/wiki/Muscle_relaxant" title="Muscle relaxant">muscle relaxants</a> (<a href="/wiki/ATC_code_M03" title="ATC code M03">M03</a>)</div></th></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Neuromuscular-blocking_drugs" class="mw-redirect" title="Neuromuscular-blocking drugs">Peripherally acting</a><br />(primarily <a href="/wiki/Nicotinic_antagonist" title="Nicotinic antagonist">antinicotinic</a>,<br /><a href="/wiki/Neuromuscular-blocking_drugs" class="mw-redirect" title="Neuromuscular-blocking drugs">NMJ block</a>)</th><td class="navbox-list-with-group navbox-list navbox-odd hlist" style="width:100%;padding:0"><div style="padding:0 0.25em"></div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Neuromuscular_nondepolarizing_agent" class="mw-redirect" title="Neuromuscular nondepolarizing agent">Non-depolarizing</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"></div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><th id="Curare_alkaloids" scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Curare" title="Curare">Curare</a> <a href="/wiki/Alkaloid" title="Alkaloid">alkaloids</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Alcuronium_chloride" title="Alcuronium chloride">Alcuronium</a></li> <li><a href="/wiki/Dimethyltubocurarinium_chloride" title="Dimethyltubocurarinium chloride">Dimethyltubocurarine</a></li> <li><a href="/wiki/Tubocurarine_chloride" title="Tubocurarine chloride">Tubocurarine</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Quaternary_ammonium_muscle_relaxants" class="mw-redirect" title="Quaternary ammonium muscle relaxants">4° ammonium agents</a></th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><i>ultra-short duration:</i> <a href="/wiki/Gantacurium_chloride" title="Gantacurium chloride">Gantacurium</a></li></ul> <ul><li><i>short duration</i>: <a href="/wiki/Rapacuronium_bromide" title="Rapacuronium bromide">Rapacuronium</a></li> <li><a href="/wiki/Mivacurium_chloride" title="Mivacurium chloride">Mivacurium</a></li> <li><a href="/wiki/Candocuronium_iodide" title="Candocuronium iodide">Chandonium</a></li></ul> <ul><li><i>intermediate duration:</i> <a href="/wiki/Atracurium_besilate" title="Atracurium besilate">Atracurium</a></li> <li><a href="/wiki/Cisatracurium_besilate" title="Cisatracurium besilate">Cisatracurium</a></li> <li><a href="/wiki/Fazadinium_bromide" title="Fazadinium bromide">Fazadinium</a></li> <li><a href="/wiki/Rocuronium_bromide" title="Rocuronium bromide">Rocuronium</a></li> <li><a href="/wiki/Vecuronium_bromide" title="Vecuronium bromide">Vecuronium</a></li></ul> <ul><li><i>long duration:</i> <a href="/wiki/Doxacurium_chloride" title="Doxacurium chloride">Doxacurium</a></li> <li><a href="/wiki/Dimethyltubocurarine" class="mw-redirect" title="Dimethyltubocurarine">Dimethyltubocurarine</a></li> <li><a href="/wiki/Pancuronium_bromide" title="Pancuronium bromide">Pancuronium</a></li> <li><a href="/wiki/Pipecuronium_bromide" title="Pipecuronium bromide">Pipecuronium</a></li> <li><a href="/wiki/Laudexium_metilsulfate" title="Laudexium metilsulfate">Laudexium</a></li> <li><a href="/wiki/Gallamine_triethiodide" title="Gallamine triethiodide">Gallamine</a></li></ul> <ul><li><i>unsorted:</i> <a href="/wiki/Hexafluronium_bromide" title="Hexafluronium bromide">Hexafluronium</a> (Hexafluorenium)</li></ul> </div></td></tr></tbody></table><div></div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Neuromuscular_depolarizing_agent" class="mw-redirect" title="Neuromuscular depolarizing agent">Depolarizing</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><i><a href="/wiki/Choline" title="Choline">Choline derivatives</a>:</i> <a href="/wiki/Suxamethonium_chloride" title="Suxamethonium chloride">Suxamethonium</a> (Succinylcholine)</li></ul> <ul><li><i>Polyalkylene derivatives:</i> <a href="/wiki/Hexamethonium" title="Hexamethonium">Hexamethonium</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Acetylcholine#Release_inhibitors" title="Acetylcholine">ACh release inhibitors</a></th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Botulinum_toxin" title="Botulinum toxin">Botulinum toxin</a></li></ul> </div></td></tr></tbody></table><div></div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Muscle_relaxant#Spasmolytics" title="Muscle relaxant">Centrally acting</a></th><td class="navbox-list-with-group navbox-list navbox-odd hlist" style="width:100%;padding:0"><div style="padding:0 0.25em"></div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Carbamic_acid" title="Carbamic acid">Carbamic acid</a> esters</th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Carisoprodol" title="Carisoprodol">Carisoprodol</a></li> <li><a href="/wiki/Cyclarbamate" title="Cyclarbamate">Cyclarbamate</a></li> <li><a href="/wiki/Difebarbamate" title="Difebarbamate">Difebarbamate</a></li> <li><a href="/wiki/Febarbamate" title="Febarbamate">Febarbamate</a></li> <li><a href="/wiki/Meprobamate" title="Meprobamate">Meprobamate</a></li> <li><a href="/wiki/Phenprobamate" title="Phenprobamate">Phenprobamate</a></li> <li><a href="/wiki/Styramate" title="Styramate">Styramate</a></li> <li><a href="/wiki/Tybamate" title="Tybamate">Tybamate</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Benzodiazepine" title="Benzodiazepine">Benzodiazepines</a></th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Bromazepam" title="Bromazepam">Bromazepam</a></li> <li><a href="/wiki/Diazepam" title="Diazepam">Diazepam</a></li> <li><a href="/wiki/Clonazepam" title="Clonazepam">Clonazepam</a></li> <li><a href="/wiki/Flunitrazepam" title="Flunitrazepam">Flunitrazepam</a></li> <li><a href="/wiki/Lorazepam" title="Lorazepam">Lorazepam</a></li> <li><a href="/wiki/Nitrazepam" title="Nitrazepam">Nitrazepam</a></li> <li><a href="/wiki/Temazepam" title="Temazepam">Temazepam</a></li> <li><a href="/wiki/Tetrazepam" title="Tetrazepam">Tetrazepam</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Nonbenzodiazepines" class="mw-redirect" title="Nonbenzodiazepines">Nonbenzodiazepines</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Eszopiclone" title="Eszopiclone">Eszopiclone</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Thienodiazepine" title="Thienodiazepine">Thienodiazepines</a></th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Etizolam" title="Etizolam">Etizolam</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Quinazoline" title="Quinazoline">Quinazolines</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Methaqualone" title="Methaqualone">Methaqualone</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Anticholinergic" title="Anticholinergic">Anticholinergics</a> <br />(<a href="/wiki/Muscarinic_antagonist" title="Muscarinic antagonist">Antimuscarinics</a>)</th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Cyclobenzaprine" title="Cyclobenzaprine">Cyclobenzaprine</a></li> <li><a href="/wiki/Orphenadrine" title="Orphenadrine">Orphenadrine</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%">Other</th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Arbaclofen_placarbil" title="Arbaclofen placarbil">Arbaclofen placarbil</a></li> <li><a href="/wiki/Baclofen" title="Baclofen">Baclofen</a></li> <li><a href="/wiki/Chlormezanone" title="Chlormezanone">Chlormezanone</a></li> <li><a href="/wiki/Chlorphenesin" class="mw-redirect" title="Chlorphenesin">Chlorphenesin</a></li> <li><a href="/wiki/Chlorzoxazone" title="Chlorzoxazone">Chlorzoxazone</a></li> <li><a href="/wiki/Eperisone" title="Eperisone">Eperisone</a></li> <li><a href="/wiki/Fenyramidol" title="Fenyramidol">Fenyramidol</a></li> <li><a href="/wiki/Flopropione" title="Flopropione">Flopropione</a></li> <li><a href="/wiki/Gabapentin" title="Gabapentin">Gabapentin</a></li> <li><a href="/wiki/Gamma-Hydroxybutyric_acid" class="mw-redirect" title="Gamma-Hydroxybutyric acid">GHB</a></li> <li><a href="/wiki/Inaperisone" title="Inaperisone">Inaperisone</a></li> <li><a href="/wiki/Lanperisone" title="Lanperisone">Lanperisone</a></li> <li><a href="/wiki/Mephenesin" title="Mephenesin">Mephenesin</a></li> <li><a href="/wiki/Mephenoxalone" title="Mephenoxalone">Mephenoxalone</a></li> <li><a href="/wiki/Metaxalone" title="Metaxalone">Metaxalone</a></li> <li><a href="/wiki/Methocarbamol" title="Methocarbamol">Methocarbamol</a></li> <li><a href="/wiki/Phenibut" title="Phenibut">Phenibut</a></li> <li><a href="/wiki/Pregabalin" title="Pregabalin">Pregabalin</a></li> <li><a href="/wiki/Pridinol" title="Pridinol">Pridinol</a></li> <li><a href="/wiki/Promoxolane" title="Promoxolane">Promoxolane</a></li> <li><a href="/wiki/Quinine" title="Quinine">Quinine</a></li> <li><a href="/wiki/Silperisone" title="Silperisone">Silperisone</a></li> <li><a href="/wiki/Thiocolchicoside" title="Thiocolchicoside">Thiocolchicoside</a></li> <li><a href="/wiki/Tizanidine" title="Tizanidine">Tizanidine</a></li> <li><a href="/wiki/Tolperisone" title="Tolperisone">Tolperisone</a></li> <li><a href="/wiki/Zoxazolamine" title="Zoxazolamine">Zoxazolamine</a></li></ul> </div></td></tr></tbody></table><div></div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Muscle_relaxant#Terminology" title="Muscle relaxant">Directly acting</a></th><td class="navbox-list-with-group navbox-list navbox-even hlist" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Dantrolene" title="Dantrolene">Dantrolene</a></li></ul> </div></td></tr></tbody></table></div> <div class="navbox-styles"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1129693374"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1236075235"></div><div role="navigation" class="navbox" aria-labelledby="Acetylcholine_metabolism_and_transport_modulators" style="padding:3px"><table class="nowraplinks hlist mw-collapsible mw-collapsed navbox-inner" style="border-spacing:0;background:transparent;color:inherit"><tbody><tr><th scope="col" class="navbox-title" colspan="2"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1129693374"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1239400231"><div class="navbar plainlinks hlist navbar-mini"><ul><li class="nv-view"><a href="/wiki/Template:Acetylcholine_metabolism_and_transport_modulators" title="Template:Acetylcholine metabolism and transport modulators"><abbr title="View this template">v</abbr></a></li><li class="nv-talk"><a href="/wiki/Template_talk:Acetylcholine_metabolism_and_transport_modulators" title="Template talk:Acetylcholine metabolism and transport modulators"><abbr title="Discuss this template">t</abbr></a></li><li class="nv-edit"><a href="/wiki/Special:EditPage/Template:Acetylcholine_metabolism_and_transport_modulators" title="Special:EditPage/Template:Acetylcholine metabolism and transport modulators"><abbr title="Edit this template">e</abbr></a></li></ul></div><div id="Acetylcholine_metabolism_and_transport_modulators" style="font-size:114%;margin:0 4em"><a href="/wiki/Acetylcholine" title="Acetylcholine">Acetylcholine</a> <a href="/wiki/Metabolism" title="Metabolism">metabolism</a> and <a href="/wiki/Neurotransmitter_transporter" title="Neurotransmitter transporter">transport</a> <a href="/wiki/Receptor_modulator" title="Receptor modulator">modulators</a></div></th></tr><tr><th scope="row" class="navbox-group" style="width:1%;text-align:center;"><a href="/wiki/Enzyme" title="Enzyme">Enzyme</a><br /><small>(<a href="/wiki/Enzyme_modulator" title="Enzyme modulator">modulators</a>)</small></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"></div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><th scope="row" class="navbox-group" style="width:6em;;text-align:center;"><a href="/wiki/Choline_acetyltransferase" title="Choline acetyltransferase"><abbr title="Choline acetyltransferase">ChAT</abbr></a><span class="sr-only" style="border: 0; clip: rect(0, 0, 0, 0); clip-path: polygon(0px 0px, 0px 0px, 0px 0px); height: 1px; margin: -1px; overflow: hidden; padding: 0; position: absolute; width: 1px; white-space: nowrap;">Tooltip Choline acetyltransferase</span></th><td class="navbox-list-with-group navbox-list navbox-odd" style="padding:0"><div style="padding:0 0.25em"> <ul><li><b>Inhibitors:</b> <a href="/w/index.php?title=1-(-Benzoylethyl)pyridinium&action=edit&redlink=1" class="new" title="1-(-Benzoylethyl)pyridinium (page does not exist)">1-(-Benzoylethyl)pyridinium</a></li> <li><a href="/w/index.php?title=2-(%CE%B1-Naphthoyl)ethyltrimethylammonium&action=edit&redlink=1" class="new" title="2-(α-Naphthoyl)ethyltrimethylammonium (page does not exist)">2-(α-Naphthoyl)ethyltrimethylammonium</a></li> <li><a href="/w/index.php?title=3-Chloro-4-stillbazole&action=edit&redlink=1" class="new" title="3-Chloro-4-stillbazole (page does not exist)">3-Chloro-4-stillbazole</a></li> <li><a href="/w/index.php?title=4-(1-Naphthylvinyl)pyridine&action=edit&redlink=1" class="new" title="4-(1-Naphthylvinyl)pyridine (page does not exist)">4-(1-Naphthylvinyl)pyridine</a></li> <li><a href="/w/index.php?title=Acetylseco_hemicholinium-3&action=edit&redlink=1" class="new" title="Acetylseco hemicholinium-3 (page does not exist)">Acetylseco hemicholinium-3</a></li> <li><a href="/w/index.php?title=Acryloylcholine&action=edit&redlink=1" class="new" title="Acryloylcholine (page does not exist)">Acryloylcholine</a></li> <li><a href="/wiki/AF64A" class="mw-redirect" title="AF64A">AF64A</a></li> <li><a href="/w/index.php?title=(E)-1-Methyl-4-(1-naphthylvinyl)-1,2,3,6-tetrahydropyridine&action=edit&redlink=1" class="new" title="(E)-1-Methyl-4-(1-naphthylvinyl)-1,2,3,6-tetrahydropyridine (page does not exist)">B115</a></li> <li><a href="/w/index.php?title=(2-Benzoylethyl)trimethylammonium&action=edit&redlink=1" class="new" title="(2-Benzoylethyl)trimethylammonium (page does not exist)">BETA</a></li> <li><a href="/w/index.php?title=N,N-Dimethylamino-2-ethoxyimino-2-adamantane&action=edit&redlink=1" class="new" title="N,N-Dimethylamino-2-ethoxyimino-2-adamantane (page does not exist)">CM-54,903</a></li> <li><a href="/w/index.php?title=N,N-Dimethylaminoethylacrylate&action=edit&redlink=1" class="new" title="N,N-Dimethylaminoethylacrylate (page does not exist)">N,N-Dimethylaminoethylacrylate</a></li> <li><a href="/w/index.php?title=N,N-Dimethylaminoethylchloroacetate&action=edit&redlink=1" class="new" title="N,N-Dimethylaminoethylchloroacetate (page does not exist)">N,N-Dimethylaminoethylchloroacetate</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:6em;;text-align:center;"><a href="/wiki/Acetylcholinesterase" title="Acetylcholinesterase"><abbr title="Acetylcholinesterase">AChE</abbr></a><span class="sr-only" style="border: 0; clip: rect(0, 0, 0, 0); clip-path: polygon(0px 0px, 0px 0px, 0px 0px); height: 1px; margin: -1px; overflow: hidden; padding: 0; position: absolute; width: 1px; white-space: nowrap;">Tooltip Acetylcholinesterase</span></th><td class="navbox-list-with-group navbox-list navbox-even" style="padding:0"><div style="padding:0 0.25em"> <ul><li><b><a href="/wiki/Acetylcholinesterase_inhibitor" title="Acetylcholinesterase inhibitor">Inhibitors</a>:</b> <i>Reversible:</i> Carbamates: <a href="/wiki/Aldicarb" title="Aldicarb">Aldicarb</a></li> <li><a href="/wiki/Aminocarb" title="Aminocarb">Aminocarb</a></li> <li><a href="/wiki/Bendiocarb" title="Bendiocarb">Bendiocarb</a></li> <li><a href="/w/index.php?title=Bufencarb&action=edit&redlink=1" class="new" title="Bufencarb (page does not exist)">Bufencarb</a></li> <li><a href="/wiki/Carbaryl" title="Carbaryl">Carbaryl</a></li> <li><a href="/wiki/Carbendazim" title="Carbendazim">Carbendazim</a></li> <li><a href="/w/index.php?title=Carbetamide&action=edit&redlink=1" class="new" title="Carbetamide (page does not exist)">Carbetamide</a></li> <li><a href="/wiki/Carbofuran" title="Carbofuran">Carbofuran</a></li> <li><a href="/wiki/Carbosulfan" title="Carbosulfan">Carbosulfan</a></li> <li><a href="/w/index.php?title=Chlorbufam&action=edit&redlink=1" class="new" title="Chlorbufam (page does not exist)">Chlorbufam</a></li> <li><a href="/w/index.php?title=Chloropropham&action=edit&redlink=1" class="new" title="Chloropropham (page does not exist)">Chloropropham</a></li> <li><a href="/wiki/Dimetilan" title="Dimetilan">Dimetilan</a></li> <li><a href="/wiki/Ethienocarb" class="mw-redirect" title="Ethienocarb">Ethienocarb</a></li> <li><a href="/wiki/Ethiofencarb" title="Ethiofencarb">Ethiofencarb</a></li> <li><a href="/wiki/Fenobucarb" title="Fenobucarb">Fenobucarb</a></li> <li><a href="/wiki/Formetanate" title="Formetanate">Formetanate</a></li> <li><a href="/wiki/Formparanate" title="Formparanate">Formparanate</a></li> <li><a href="/wiki/Methiocarb" title="Methiocarb">Methiocarb</a></li> <li><a href="/wiki/Methomyl" title="Methomyl">Methomyl</a></li> <li><a href="/wiki/Metolcarb" title="Metolcarb">Metolcarb</a></li> <li><a href="/wiki/Miotine" title="Miotine">Miotine</a></li> <li><a href="/wiki/Oxamyl" title="Oxamyl">Oxamyl</a></li> <li><a href="/w/index.php?title=Phenmedipham&action=edit&redlink=1" class="new" title="Phenmedipham (page does not exist)">Phenmedipham</a></li> <li><a href="/w/index.php?title=Pinmicarb&action=edit&redlink=1" class="new" title="Pinmicarb (page does not exist)">Pinmicarb</a></li> <li><a href="/wiki/Pirimicarb" title="Pirimicarb">Pirimicarb</a></li> <li><a href="/wiki/Promecarb" title="Promecarb">Promecarb</a></li> <li><a href="/wiki/Propamocarb" title="Propamocarb">Propamocarb</a></li> <li><a href="/w/index.php?title=Propham&action=edit&redlink=1" class="new" title="Propham (page does not exist)">Propham</a></li> <li><a href="/wiki/Propoxur" title="Propoxur">Propoxur</a></li> <li><a href="/w/index.php?title=Thiodicarb&action=edit&redlink=1" class="new" title="Thiodicarb (page does not exist)">Thiodicarb</a></li> <li><a href="/wiki/Thiofanox" title="Thiofanox">Thiofanox</a>; Stigmines: <a href="/wiki/Distigmine" title="Distigmine">Distigmine</a></li> <li><a href="/w/index.php?title=Eptastigmine&action=edit&redlink=1" class="new" title="Eptastigmine (page does not exist)">Eptastigmine</a></li> <li><a href="/w/index.php?title=Ganstigmine&action=edit&redlink=1" class="new" title="Ganstigmine (page does not exist)">Ganstigmine</a></li> <li><a href="/wiki/Neostigmine" title="Neostigmine">Neostigmine</a> <a href="/wiki/Neostigmine/glycopyrronium_bromide" title="Neostigmine/glycopyrronium bromide">+glycopyrronium bromide</a></li> <li><a href="/wiki/Phenserine" title="Phenserine">Phenserine</a></li> <li><a href="/wiki/Physostigmine" title="Physostigmine">Physostigmine</a></li> <li><a href="/wiki/Pyridostigmine" title="Pyridostigmine">Pyridostigmine</a></li> <li><a href="/w/index.php?title=Quilostigmine&action=edit&redlink=1" class="new" title="Quilostigmine (page does not exist)">Quilostigmine</a></li> <li><a href="/wiki/Rivastigmine" title="Rivastigmine">Rivastigmine</a></li> <li><a href="/w/index.php?title=Terestigmine&action=edit&redlink=1" class="new" title="Terestigmine (page does not exist)">Terestigmine</a>; Others: <a href="/wiki/Acotiamide" title="Acotiamide">Acotiamide</a></li> <li><a href="/wiki/Ambenonium" class="mw-redirect" title="Ambenonium">Ambenonium</a></li> <li><a href="/wiki/Caffeine" title="Caffeine">Caffeine</a></li> <li><a href="/wiki/Donepezil" title="Donepezil">Donepezil</a></li> <li><a href="/wiki/EA-3990" title="EA-3990">EA-3990</a></li> <li><a href="/wiki/EA-4056" title="EA-4056">EA-4056</a></li> <li><a href="/wiki/Edrophonium" title="Edrophonium">Edrophonium</a></li> <li><a href="/wiki/Galantamine" title="Galantamine">Galantamine</a></li> <li><a href="/wiki/Huperzine_A" title="Huperzine A">Huperzine A</a></li> <li><a href="/w/index.php?title=Huprine_W&action=edit&redlink=1" class="new" title="Huprine W (page does not exist)">Huprine W</a></li> <li><a href="/wiki/Huprine_X" title="Huprine X">Huprine X</a></li> <li><a href="/w/index.php?title=Huprine_Y&action=edit&redlink=1" class="new" title="Huprine Y (page does not exist)">Huprine Y</a></li> <li><a href="/wiki/Ipidacrine" title="Ipidacrine">Ipidacrine</a></li> <li><a href="/wiki/Itopride" title="Itopride">Itopride</a></li> <li><a href="/wiki/Ladostigil" title="Ladostigil">Ladostigil</a></li> <li><a href="/wiki/Minaprine" title="Minaprine">Minaprine</a></li> <li><a href="/wiki/Octamethylene-bis(5-dimethylcarbamoxyisoquinolinium_bromide)" title="Octamethylene-bis(5-dimethylcarbamoxyisoquinolinium bromide)">Octamethylene-bis(5-dimethylcarbamoxyisoquinolinium bromide)</a></li> <li><a href="/wiki/T-1123" title="T-1123">T-1123</a></li> <li><a href="/wiki/T-1152" title="T-1152">T-1152</a></li> <li><a href="/wiki/T-1194" title="T-1194">T-1194</a></li> <li><a href="/wiki/TL-599" title="TL-599">TL-599</a></li> <li><a href="/wiki/TL-1238" title="TL-1238">TL-1238</a></li> <li><a href="/wiki/Tacrine" title="Tacrine">Tacrine</a></li> <li><a href="/w/index.php?title=Zanapezil&action=edit&redlink=1" class="new" title="Zanapezil (page does not exist)">Zanapezil</a></li></ul> <ul><li><i>Irreversible:</i> Organophosphates: <a href="/wiki/2-Ethoxycarbonyl-1-methylvinyl_cyclohexyl_methylphosphonate" title="2-Ethoxycarbonyl-1-methylvinyl cyclohexyl methylphosphonate">2-Ethoxycarbonyl-1-methylvinyl cyclohexyl methylphosphonate</a></li> <li><a href="/wiki/Acephate" title="Acephate">Acephate</a></li> <li><a href="/wiki/Armine_(chemical)" title="Armine (chemical)">Armine</a></li> <li><a href="/wiki/Azinphos-ethyl" title="Azinphos-ethyl">Azinphos-ethyl</a></li> <li><a href="/wiki/Azinphos-methyl" title="Azinphos-methyl">Azinphos-methyl</a></li> <li><a href="/wiki/BAY-29952" title="BAY-29952">BAY-29952</a></li> <li><a href="/wiki/Bensulide" title="Bensulide">Bensulide</a></li> <li><a href="/wiki/Cadusafos" title="Cadusafos">Cadusafos</a></li> <li><a href="/wiki/Carbophenothion" title="Carbophenothion">Carbophenothion</a></li> <li><a href="/wiki/Chlorethoxyfos" title="Chlorethoxyfos">Chlorethoxyfos</a></li> <li><a href="/wiki/Chlorfenvinphos" title="Chlorfenvinphos">Chlorfenvinphos</a></li> <li><a href="/wiki/Chlorpyrifos" title="Chlorpyrifos">Chlorpyrifos</a></li> <li><a href="/wiki/Chlorpyrifos-methyl" class="mw-redirect" title="Chlorpyrifos-methyl">Chlorpyrifos-methyl</a></li> <li><a href="/wiki/Coumaphos" title="Coumaphos">Coumaphos</a></li> <li><a href="/wiki/Crotylsarin" title="Crotylsarin">Crotylsarin</a></li> <li><a href="/wiki/Cyanophos" title="Cyanophos">Cyanophos</a></li> <li><a href="/wiki/Cyclosarin" title="Cyclosarin">Cyclosarin (GF)</a></li> <li><a href="/wiki/Demephion" title="Demephion">Demephion</a></li> <li><a href="/wiki/Demeton" title="Demeton">Demeton</a></li> <li><a href="/wiki/Demeton-S-methyl" title="Demeton-S-methyl">Demeton-S-methyl</a></li> <li><a href="/wiki/Dialifor" title="Dialifor">Dialifor</a></li> <li><a href="/wiki/Diazinon" title="Diazinon">Diazinon</a></li> <li><a href="/wiki/Dichlorvos" title="Dichlorvos">Dichlorvos</a></li> <li><a href="/wiki/Dicrotophos" title="Dicrotophos">Dicrotophos</a></li> <li><a href="/wiki/Dicyclohexyl_phosphorofluoridate" title="Dicyclohexyl phosphorofluoridate">Dicyclohexyl phosphorofluoridate</a></li> <li><a href="/wiki/Diisopropylphosphate" title="Diisopropylphosphate">Diisopropylphosphate</a></li> <li><a href="/wiki/Diisopropyl_fluorophosphate" title="Diisopropyl fluorophosphate">Diisopropyl fluorophosphate</a></li> <li><a href="/wiki/Dimefox" title="Dimefox">Dimefox</a></li> <li><a href="/wiki/Dimethoate" title="Dimethoate">Dimethoate</a></li> <li><a href="/wiki/Dimethyl_4-(methylthio)phenyl_phosphate" title="Dimethyl 4-(methylthio)phenyl phosphate">Dimethyl 4-(methylthio)phenyl phosphate</a></li> <li><a href="/wiki/Dioxathion" title="Dioxathion">Dioxathion</a></li> <li><a href="/wiki/Disulfoton" title="Disulfoton">Disulfoton</a></li> <li><a href="/wiki/EA-2012" title="EA-2012">EA-2012</a></li> <li><a href="/wiki/EA-2054" title="EA-2054">EA-2054</a></li> <li><a href="/wiki/EA-2098" title="EA-2098">EA-2098</a></li> <li><a href="/wiki/EA-2192" title="EA-2192">EA-2192</a></li> <li><a href="/wiki/EA-2613" title="EA-2613">EA-2613</a></li> <li><a href="/wiki/EA-3148" title="EA-3148">EA-3148</a></li> <li><a href="/wiki/EA-4352" title="EA-4352">EA-4352</a></li> <li><a href="/wiki/Echothiophate" title="Echothiophate">Echothiophate</a></li> <li><a href="/wiki/Ethylsarin" title="Ethylsarin">Ethylsarin (GE)</a></li> <li><a href="/wiki/Endothion" title="Endothion">Endothion</a></li> <li><a href="/wiki/EPN_(insecticide)" title="EPN (insecticide)">EPN</a></li> <li><a href="/wiki/Ethion" title="Ethion">Ethion</a></li> <li><a href="/wiki/Ethoprop" class="mw-redirect" title="Ethoprop">Ethoprop</a></li> <li><a href="/wiki/Fenamiphos" title="Fenamiphos">Fenamiphos</a></li> <li><a href="/wiki/Fenitrothion" title="Fenitrothion">Fenitrothion</a></li> <li><a href="/wiki/Fenthion" title="Fenthion">Fenthion</a></li> <li><a href="/wiki/Fluorotabun" title="Fluorotabun">Fluorotabun</a></li> <li><a href="/wiki/Fonofos" title="Fonofos">Fonofos</a></li> <li><a href="/wiki/Formothion" title="Formothion">Formothion</a></li> <li><a href="/w/index.php?title=Fosthiazate&action=edit&redlink=1" class="new" title="Fosthiazate (page does not exist)">Fosthiazate</a></li> <li><a href="/wiki/GD-42" title="GD-42">GD-42</a></li> <li><a href="/wiki/GH_(nerve_agent)" title="GH (nerve agent)">GH</a></li> <li><a href="/w/index.php?title=GT-45&action=edit&redlink=1" class="new" title="GT-45 (page does not exist)">GT-45</a></li> <li><a href="/wiki/GV_(nerve_agent)" title="GV (nerve agent)">GV</a></li> <li><a href="/wiki/Guanitoxin" title="Guanitoxin">Guanitoxin</a></li> <li><a href="/wiki/Hexaethyl_tetraphosphate" title="Hexaethyl tetraphosphate">Hexaethyl tetraphosphate (HETP)</a></li> <li><a href="/wiki/Isofluorophate" class="mw-redirect" title="Isofluorophate">Isofluorophate</a></li> <li><a href="/wiki/Isoxathion" title="Isoxathion">Isoxathion</a></li> <li><a href="/wiki/Leptophos" title="Leptophos">Leptophos</a></li> <li><a href="/wiki/Malaoxon" title="Malaoxon">Malaoxon</a></li> <li><a href="/wiki/Malathion" title="Malathion">Malathion</a></li> <li><a href="/w/index.php?title=Mazidox&action=edit&redlink=1" class="new" title="Mazidox (page does not exist)">Mazidox</a></li> <li><a href="/wiki/Methamidophos" title="Methamidophos">Methamidophos</a></li> <li><a href="/wiki/Methidathion" title="Methidathion">Methidathion</a></li> <li><a href="/wiki/Methyl_phenkapton" title="Methyl phenkapton">Methyl phenkapton</a></li> <li><a href="/wiki/Methylfluorophosphonylcholine" title="Methylfluorophosphonylcholine">Methylfluorophosphonylcholine (MFPCh)</a></li> <li><a href="/wiki/Metrifonate" title="Metrifonate">Metrifonate</a></li> <li><a href="/wiki/Mevinphos" title="Mevinphos">Mevinphos</a></li> <li><a href="/wiki/Mipafox" title="Mipafox">Mipafox</a></li> <li><a href="/wiki/Monocrotophos" title="Monocrotophos">Monocrotophos</a></li> <li><a href="/wiki/MSPI_(nerve_agent)" title="MSPI (nerve agent)">MSPI</a></li> <li><a href="/wiki/Naled" title="Naled">Naled</a></li> <li><a href="/wiki/Novichok_agent" class="mw-redirect" title="Novichok agent">Novichok agent</a></li> <li><a href="/wiki/Omethoate" title="Omethoate">Omethoate</a></li> <li><a href="/wiki/Oxydemeton-methyl" title="Oxydemeton-methyl">Oxydemeton-methyl</a></li> <li><a href="/wiki/Paraoxon" title="Paraoxon">Paraoxon</a></li> <li><a href="/wiki/Parathion" title="Parathion">Parathion</a></li> <li><a href="/wiki/Parathion-methyl" class="mw-redirect" title="Parathion-methyl">Parathion-methyl</a></li> <li><a href="/wiki/Phorate" title="Phorate">Phorate</a></li> <li><a href="/wiki/Phosalone" title="Phosalone">Phosalone</a></li> <li><a href="/wiki/Phosfolan" title="Phosfolan">Phosfolan</a></li> <li><a href="/wiki/Phosmet" title="Phosmet">Phosmet</a></li> <li><a href="/wiki/Phosphamidon" title="Phosphamidon">Phosphamidon</a></li> <li><a href="/wiki/Phoxim" title="Phoxim">Phoxim</a></li> <li><a href="/wiki/Pirimiphos-methyl" title="Pirimiphos-methyl">Pirimiphos-methyl</a></li> <li><a href="/wiki/Profenofos" title="Profenofos">Profenofos</a></li> <li><a href="/wiki/Prothoate" title="Prothoate">Prothoate</a></li> <li><a href="/wiki/R-16661" title="R-16661">R-16661</a></li> <li><a href="/w/index.php?title=Ro_3-0340&action=edit&redlink=1" class="new" title="Ro 3-0340 (page does not exist)">Ro 3-0340</a></li> <li><a href="/w/index.php?title=Ro_3-0346&action=edit&redlink=1" class="new" title="Ro 3-0346 (page does not exist)">Ro 3-0346</a></li> <li><a href="/w/index.php?title=Ro_3-0347&action=edit&redlink=1" class="new" title="Ro 3-0347 (page does not exist)">Ro 3-0347</a></li> <li><a href="/w/index.php?title=Ro_3-0351&action=edit&redlink=1" class="new" title="Ro 3-0351 (page does not exist)">Ro 3-0351</a></li> <li><a href="/w/index.php?title=Ro_3-0352&action=edit&redlink=1" class="new" title="Ro 3-0352 (page does not exist)">Ro 3-0352</a></li> <li><a href="/w/index.php?title=Ro_3-0397&action=edit&redlink=1" class="new" title="Ro 3-0397 (page does not exist)">Ro 3-0397</a></li> <li><a href="/w/index.php?title=Ro_3-0411&action=edit&redlink=1" class="new" title="Ro 3-0411 (page does not exist)">Ro 3-0411</a></li> <li><a href="/wiki/Ro_3-0412" title="Ro 3-0412">Ro 3-0412</a></li> <li><a href="/w/index.php?title=Ro_3-0417&action=edit&redlink=1" class="new" title="Ro 3-0417 (page does not exist)">Ro 3-0417</a></li> <li><a href="/wiki/Ro_3-0419" title="Ro 3-0419">Ro 3-0419</a></li> <li><a href="/wiki/Ro_3-0422" title="Ro 3-0422">Ro 3-0422</a></li> <li><a href="/w/index.php?title=Ro_3-0433&action=edit&redlink=1" class="new" title="Ro 3-0433 (page does not exist)">Ro 3-0433</a></li> <li><a href="/w/index.php?title=Ronnel&action=edit&redlink=1" class="new" title="Ronnel (page does not exist)">Ronnel</a></li> <li><a href="/wiki/Sarin" title="Sarin">Sarin (GB)</a></li> <li><a href="/wiki/Schradan" title="Schradan">Schradan</a></li> <li><a href="/wiki/Soman" title="Soman">Soman (GD)</a></li> <li><a href="/wiki/Sulfotep" title="Sulfotep">Sulfotep (TEDP)</a></li> <li><a href="/wiki/Tabun_(nerve_agent)" title="Tabun (nerve agent)">Tabun (GA)</a></li> <li><a href="/wiki/Tebupirimfos" title="Tebupirimfos">Tebupirimfos</a></li> <li><a href="/wiki/Temefos" title="Temefos">Temefos</a></li> <li><a href="/wiki/Terbufos" title="Terbufos">Terbufos</a></li> <li><a href="/wiki/Tetrachlorvinphos" title="Tetrachlorvinphos">Tetrachlorvinphos</a></li> <li><a href="/wiki/Tetraethyl_pyrophosphate" title="Tetraethyl pyrophosphate">Tetraethyl pyrophosphate (TEPP)</a></li> <li><a href="/wiki/Triazofos" title="Triazofos">Triazofos</a></li> <li><a href="/w/index.php?title=Tribufos&action=edit&redlink=1" class="new" title="Tribufos (page does not exist)">Tribufos</a></li> <li><a href="/wiki/Trichlorfon" class="mw-redirect" title="Trichlorfon">Trichlorfon</a></li> <li><a href="/wiki/Trichloronate" title="Trichloronate">Trichloronate</a></li> <li><a href="/wiki/Tricresyl_phosphate" title="Tricresyl phosphate">Tricresyl phosphate</a></li> <li><a href="/wiki/VE_(nerve_agent)" title="VE (nerve agent)">VE</a></li> <li><a href="/wiki/VG_(nerve_agent)" title="VG (nerve agent)">VG</a></li> <li><a href="/wiki/VM_(nerve_agent)" title="VM (nerve agent)">VM</a></li> <li><a href="/wiki/VP_(nerve_agent)" class="mw-redirect" title="VP (nerve agent)">VP</a></li> <li><a href="/wiki/VS_(nerve_agent)" title="VS (nerve agent)">VS</a></li> <li><a href="/wiki/VR_(nerve_agent)" title="VR (nerve agent)">VR</a></li> <li><a href="/wiki/VX_(nerve_agent)" title="VX (nerve agent)">VX</a>; Others: <a href="/wiki/Demecarium" class="mw-redirect" title="Demecarium">Demecarium</a></li> <li><a href="/wiki/Fasciculin" title="Fasciculin">Fasciculins (green mamba toxins)</a> (<a href="/w/index.php?title=Fasciculin_1&action=edit&redlink=1" class="new" title="Fasciculin 1 (page does not exist)">1</a>, <a href="/w/index.php?title=Fasciculin_2&action=edit&redlink=1" class="new" title="Fasciculin 2 (page does not exist)">2</a>, <a href="/w/index.php?title=Fasciculin_3&action=edit&redlink=1" class="new" title="Fasciculin 3 (page does not exist)">3</a>, <a href="/w/index.php?title=Fasciculin_4&action=edit&redlink=1" class="new" title="Fasciculin 4 (page does not exist)">4</a>)</li> <li><a href="/wiki/Onchidal" title="Onchidal">Onchidal</a> (<i><a href="/wiki/Onchidella_binneyi" title="Onchidella binneyi">Onchidella binneyi</a></i>)</li> <li><a href="/wiki/Methanesulfonyl_fluoride" title="Methanesulfonyl fluoride">Methanesulfonyl fluoride</a></li></ul> <ul><li><i>Unsorted:</i> <a href="/wiki/%CE%91-Pinene" title="Α-Pinene">α-Pinene</a></li> <li><a href="/wiki/%CE%91-Viniferin" title="Α-Viniferin">α-Viniferin</a></li> <li><a href="/wiki/Affinine" title="Affinine">Affinine</a></li> <li><a href="/wiki/Affinisine" title="Affinisine">Affinisine</a></li> <li><a href="/wiki/Arisugacin_A" title="Arisugacin A">Arisugacin A</a></li> <li><a href="/wiki/Bulbocapnine" title="Bulbocapnine">Bulbocapnine</a></li> <li><a href="/wiki/Conodurine" title="Conodurine">Conodurine</a></li> <li><a href="/wiki/Coronaridine" title="Coronaridine">Coronaridine</a></li> <li><a href="/wiki/Corydaline" title="Corydaline">Corydaline</a></li> <li><a href="/wiki/Corynoline" title="Corynoline">Corynoline</a></li> <li><a href="/wiki/Crimidine" title="Crimidine">Crimidine</a></li> <li><a href="/wiki/Cyclanoline" title="Cyclanoline">Cyclanoline</a></li> <li><a href="/wiki/Cymserine" title="Cymserine">Cymserine</a></li> <li><a href="/wiki/Harmaline" title="Harmaline">Harmaline</a></li> <li><a href="/wiki/Kobophenol_A" title="Kobophenol A">Kobophenol A</a></li> <li><a href="/wiki/Lactucopicrin" title="Lactucopicrin">Lactucopicrin</a></li> <li><a href="/wiki/Lycorine" title="Lycorine">Lycorine</a></li> <li><a href="/wiki/Phosacetim" title="Phosacetim">Phosacetim</a></li> <li><a href="/wiki/Rosmarinic_acid" title="Rosmarinic acid">Rosmarinic acid</a></li> <li><a href="/wiki/Stercuronium_iodide" title="Stercuronium iodide">Stercuronium iodide</a></li> <li><a href="/wiki/Taspine" title="Taspine">Taspine</a></li> <li><a href="/wiki/Tetrahydrocannabinol" title="Tetrahydrocannabinol">Tetrahydrocannabinol</a></li> <li><a href="/wiki/Ungeremine" title="Ungeremine">Ungeremine</a></li> <li><a href="/wiki/Ungiminorine" title="Ungiminorine">Ungiminorine</a></li> <li><a href="/wiki/Dimethylcarbamoyl_fluoride" title="Dimethylcarbamoyl fluoride">Dimethylcarbamoyl fluoride</a></li> <li><a href="/wiki/BW284C51" title="BW284C51">BW284C51</a></li> <li><a href="/wiki/TMTFA" title="TMTFA">TMTFA</a></li> <li><a href="/wiki/3152_CT" title="3152 CT">3152 CT</a></li></ul> <ul><li><a href="/wiki/Cholinesterase_reactivator" title="Cholinesterase reactivator">Reactivators</a>: <a href="/wiki/Asoxime_chloride" title="Asoxime chloride">Asoxime chloride</a></li> <li><a href="/w/index.php?title=Methoxime&action=edit&redlink=1" class="new" title="Methoxime (page does not exist)">Methoxime</a></li> <li><a href="/wiki/Obidoxime" title="Obidoxime">Obidoxime</a></li> <li><a href="/wiki/Pralidoxime" title="Pralidoxime">Pralidoxime</a></li> <li><a href="/wiki/Trimedoxime_bromide" title="Trimedoxime bromide">Trimedoxime bromide</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:6em;;text-align:center;"><a href="/wiki/Butyrylcholinesterase" title="Butyrylcholinesterase"><abbr title="Butyrylcholinesterase">BChE</abbr></a><span class="sr-only" style="border: 0; clip: rect(0, 0, 0, 0); clip-path: polygon(0px 0px, 0px 0px, 0px 0px); height: 1px; margin: -1px; overflow: hidden; padding: 0; position: absolute; width: 1px; white-space: nowrap;">Tooltip Butyrylcholinesterase</span></th><td class="navbox-list-with-group navbox-list navbox-odd" style="padding:0"><div style="padding:0 0.25em"> <ul><li><b>Inhibitors:</b> <a href="/wiki/Affinine" title="Affinine">Affinine</a></li> <li><a href="/wiki/Affinisine" title="Affinisine">Affinisine</a></li> <li><a href="/wiki/Conodurine" title="Conodurine">Conodurine</a></li> <li><a href="/wiki/Cymserine" title="Cymserine">Cymserine</a></li> <li><a href="/wiki/Ladostigil" title="Ladostigil">Ladostigil</a></li> <li><a href="/wiki/Profenamine" title="Profenamine">Profenamine (ethopropazine)</a></li> <li><a href="/wiki/Rivastigmine" title="Rivastigmine">Rivastigmine</a></li> <li><a href="/wiki/Tacrine" title="Tacrine">Tacrine</a></li> <li><a href="/w/index.php?title=ZINC-12613047&action=edit&redlink=1" class="new" title="ZINC-12613047 (page does not exist)">ZINC-12613047</a></li> <li>Many of the other AChE inhibitors listed above</li></ul> </div></td></tr></tbody></table><div></div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%;text-align:center;"><a href="/wiki/Neurotransmitter_transporter" title="Neurotransmitter transporter">Transporter</a><br /><small>(<a href="/wiki/Transporter_modulator" class="mw-redirect" title="Transporter modulator">modulators</a>)</small></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"></div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><th scope="row" class="navbox-group" style="width:6em;;text-align:center;"><a href="/wiki/Choline_transporter" title="Choline transporter"><abbr title="Choline transporter">CHT</abbr></a><span class="sr-only" style="border: 0; clip: rect(0, 0, 0, 0); clip-path: polygon(0px 0px, 0px 0px, 0px 0px); height: 1px; margin: -1px; overflow: hidden; padding: 0; position: absolute; width: 1px; white-space: nowrap;">Tooltip Choline transporter</span></th><td class="navbox-list-with-group navbox-list navbox-even" style="padding:0"><div style="padding:0 0.25em"> <ul><li><b>Inhibitors:</b> <a href="/wiki/Hemicholinium-3" title="Hemicholinium-3">Hemicholinium-3 (hemicholine)</a></li> <li><a href="/wiki/Triethylcholine" title="Triethylcholine">Triethylcholine</a></li></ul> <ul><li><b>Enhancers:</b> <a href="/wiki/Coluracetam" title="Coluracetam">Coluracetam</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:6em;;text-align:center;"><a href="/wiki/Vesicular_acetylcholine_transporter" title="Vesicular acetylcholine transporter"><abbr title="Vesicular acetylcholine transporter">VAChT</abbr></a><span class="sr-only" style="border: 0; clip: rect(0, 0, 0, 0); clip-path: polygon(0px 0px, 0px 0px, 0px 0px); height: 1px; margin: -1px; overflow: hidden; padding: 0; position: absolute; width: 1px; white-space: nowrap;">Tooltip Vesicular acetylcholine transporter</span></th><td class="navbox-list-with-group navbox-list navbox-odd" style="padding:0"><div style="padding:0 0.25em"> <ul><li><b>Inhibitors:</b> <a href="/wiki/Vesamicol" title="Vesamicol">Vesamicol</a></li></ul> </div></td></tr></tbody></table><div></div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%;text-align:center;"><a href="/wiki/Neurotransmitter_release" class="mw-redirect" title="Neurotransmitter release">Release</a><br /><small>(<a href="/wiki/Release_modulator" title="Release modulator">modulators</a>)</small></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"></div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><th scope="row" class="navbox-group" style="width:6em;;text-align:center;"><a href="/wiki/Release_inhibitor" class="mw-redirect" title="Release inhibitor">Inhibitors</a></th><td class="navbox-list-with-group navbox-list navbox-even" style="padding:0"><div style="padding:0 0.25em"> <ul><li><b><a href="/wiki/Synaptosomal-associated_protein_25" class="mw-redirect" title="Synaptosomal-associated protein 25"><abbr title="Synaptosomal-associated protein 25">SNAP-25</abbr></a><span class="sr-only" style="border: 0; clip: rect(0, 0, 0, 0); clip-path: polygon(0px 0px, 0px 0px, 0px 0px); height: 1px; margin: -1px; overflow: hidden; padding: 0; position: absolute; width: 1px; white-space: nowrap;">Tooltip Synaptosomal-associated protein 25</span> inactivators:</b> <a href="/wiki/Botulinum_toxin" title="Botulinum toxin">Botulinum toxin</a> (<a href="/wiki/Botulinum_toxin_A" class="mw-redirect" title="Botulinum toxin A">A</a>, <a href="/wiki/Botulinum_toxin_C" class="mw-redirect" title="Botulinum toxin C">C</a>, <a href="/wiki/Botulinum_toxin_E" class="mw-redirect" title="Botulinum toxin E">E</a>)</li></ul> <ul><li><b><a href="/wiki/Vesicle-associated_membrane_protein" title="Vesicle-associated membrane protein"><abbr title="Vesicle-associated membrane protein">VAMP</abbr></a><span class="sr-only" style="border: 0; clip: rect(0, 0, 0, 0); clip-path: polygon(0px 0px, 0px 0px, 0px 0px); height: 1px; margin: -1px; overflow: hidden; padding: 0; position: absolute; width: 1px; white-space: nowrap;">Tooltip Vesicle-associated membrane protein</span> inactivators:</b> <a href="/wiki/Botulinum_toxin" title="Botulinum toxin">Botulinum toxin</a> (<a href="/wiki/Botulinum_toxin_B" class="mw-redirect" title="Botulinum toxin B">B</a>, <a href="/wiki/Botulinum_toxin_D" class="mw-redirect" title="Botulinum toxin D">D</a>, <a href="/wiki/Botulinum_toxin_F" class="mw-redirect" title="Botulinum toxin F">F</a>, <a href="/wiki/Botulinum_toxin_G" class="mw-redirect" title="Botulinum toxin G">G</a>)</li></ul> <ul><li><b>Others:</b> <a href="/wiki/Bungarotoxin" title="Bungarotoxin">Bungarotoxins</a> (<a href="/wiki/Beta-Bungarotoxin" class="mw-redirect" title="Beta-Bungarotoxin">β-bungarotoxin</a>, <a href="/wiki/%CE%93-bungarotoxin" class="mw-redirect" title="Γ-bungarotoxin">γ-bungarotoxin</a>)</li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:6em;;text-align:center;"><a href="/wiki/Release_enhancer" class="mw-redirect" title="Release enhancer">Enhancers</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="padding:0"><div style="padding:0 0.25em"> <ul><li><b><a href="/wiki/Latrophilin" title="Latrophilin"><abbr title="Latrophilin">LPHN</abbr></a><span class="sr-only" style="border: 0; clip: rect(0, 0, 0, 0); clip-path: polygon(0px 0px, 0px 0px, 0px 0px); height: 1px; margin: -1px; overflow: hidden; padding: 0; position: absolute; width: 1px; white-space: nowrap;">Tooltip Latrophilin</span> agonists:</b> <a href="/wiki/Alpha-Latrotoxin" class="mw-redirect" title="Alpha-Latrotoxin">α-Latrotoxin</a></li></ul> <ul><li><b>Others:</b> Atracotoxins (e.g., <a href="/wiki/Robustoxin" class="mw-redirect" title="Robustoxin">robustoxin</a>, <a href="/wiki/Versutoxin" title="Versutoxin">versutoxin</a>)</li> <li><a href="/wiki/Crotoxin" title="Crotoxin">Crotoxin</a></li></ul> </div></td></tr></tbody></table><div></div></td></tr><tr><td class="navbox-abovebelow" colspan="2"><div> <dl><dt>See also</dt> <dd><a href="/wiki/Template:Receptor_modulators" title="Template:Receptor modulators">Receptor/signaling modulators</a></dd> <dd><a href="/wiki/Template:Muscarinic_acetylcholine_receptor_modulators" title="Template:Muscarinic acetylcholine receptor modulators">Muscarinic acetylcholine receptor modulators</a></dd> <dd><a href="/wiki/Template:Nicotinic_acetylcholine_receptor_modulators" title="Template:Nicotinic acetylcholine receptor modulators">Nicotinic acetylcholine receptor modulators</a></dd></dl> </div></td></tr></tbody></table></div> <div class="navbox-styles"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1129693374"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1236075235"></div><div role="navigation" class="navbox" aria-labelledby="Nicotinic_acetylcholine_receptor_modulators" style="padding:3px"><table class="nowraplinks hlist mw-collapsible mw-collapsed navbox-inner" style="border-spacing:0;background:transparent;color:inherit"><tbody><tr><th scope="col" class="navbox-title" colspan="2"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1129693374"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1239400231"><div class="navbar plainlinks hlist navbar-mini"><ul><li class="nv-view"><a href="/wiki/Template:Nicotinic_acetylcholine_receptor_modulators" title="Template:Nicotinic acetylcholine receptor modulators"><abbr title="View this template">v</abbr></a></li><li class="nv-talk"><a href="/wiki/Template_talk:Nicotinic_acetylcholine_receptor_modulators" title="Template talk:Nicotinic acetylcholine receptor modulators"><abbr title="Discuss this template">t</abbr></a></li><li class="nv-edit"><a href="/wiki/Special:EditPage/Template:Nicotinic_acetylcholine_receptor_modulators" title="Special:EditPage/Template:Nicotinic acetylcholine receptor modulators"><abbr title="Edit this template">e</abbr></a></li></ul></div><div id="Nicotinic_acetylcholine_receptor_modulators" style="font-size:114%;margin:0 4em"><a href="/wiki/Nicotinic_acetylcholine_receptor" title="Nicotinic acetylcholine receptor">Nicotinic acetylcholine receptor</a> <a href="/wiki/Receptor_modulator" title="Receptor modulator">modulators</a></div></th></tr><tr><th scope="row" class="navbox-group" style="width:1%;text-align:center;"><a href="/wiki/Nicotinic_acetylcholine_receptors" class="mw-redirect" title="Nicotinic acetylcholine receptors"><abbr title="Nicotinic acetylcholine receptors">nAChRs</abbr></a><span class="sr-only" style="border: 0; clip: rect(0, 0, 0, 0); clip-path: polygon(0px 0px, 0px 0px, 0px 0px); height: 1px; margin: -1px; overflow: hidden; padding: 0; position: absolute; width: 1px; white-space: nowrap;">Tooltip Nicotinic acetylcholine receptors</span></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"></div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><th scope="row" class="navbox-group" style="width:1%;text-align:center;"><a href="/wiki/Receptor_agonist" class="mw-redirect" title="Receptor agonist">Agonists</a><br />(and <a href="/wiki/Positive_allosteric_modulators" class="mw-redirect" title="Positive allosteric modulators"><abbr title="positive allosteric modulators">PAMs</abbr></a><span class="sr-only" style="border: 0; clip: rect(0, 0, 0, 0); clip-path: polygon(0px 0px, 0px 0px, 0px 0px); height: 1px; margin: -1px; overflow: hidden; padding: 0; position: absolute; width: 1px; white-space: nowrap;">Tooltip positive allosteric modulators</span>)</th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/5-Hydroxyindoleacetic_acid" title="5-Hydroxyindoleacetic acid">5-HIAA</a></li> <li><a href="/wiki/6-Chloronicotine" title="6-Chloronicotine">6-Chloronicotine</a></li> <li><a href="/wiki/A-84,543" title="A-84,543">A-84,543</a></li> <li><a href="/wiki/A-366,833" title="A-366,833">A-366,833</a></li> <li><a href="/w/index.php?title=A-582,941&action=edit&redlink=1" class="new" title="A-582,941 (page does not exist)">A-582,941</a></li> <li><a href="/w/index.php?title=A-867,744&action=edit&redlink=1" class="new" title="A-867,744 (page does not exist)">A-867,744</a></li> <li><a href="/wiki/ABT-202" title="ABT-202">ABT-202</a></li> <li><a href="/wiki/ABT-418" title="ABT-418">ABT-418</a></li> <li><a href="/w/index.php?title=ABT-560&action=edit&redlink=1" class="new" title="ABT-560 (page does not exist)">ABT-560</a></li> <li><a href="/w/index.php?title=ABT-894&action=edit&redlink=1" class="new" title="ABT-894 (page does not exist)">ABT-894</a></li> <li><a href="/wiki/Acetylcholine" title="Acetylcholine">Acetylcholine</a></li> <li><a href="/wiki/Altinicline" title="Altinicline">Altinicline</a></li> <li><a href="/wiki/Anabasine" title="Anabasine">Anabasine</a></li> <li><a href="/wiki/Anatabine" title="Anatabine">Anatabine</a></li> <li><a href="/wiki/Anatoxin-a" title="Anatoxin-a">Anatoxin-a</a></li> <li><a href="/wiki/AR-R17779" title="AR-R17779">AR-R17779</a></li> <li><a href="/wiki/Bephenium_hydroxynaphthoate" title="Bephenium hydroxynaphthoate">Bephenium hydroxynaphthoate</a></li> <li><a href="/wiki/Butinoline" title="Butinoline">Butinoline</a></li> <li><a href="/wiki/Butyrylcholine" title="Butyrylcholine">Butyrylcholine</a></li> <li><a href="/wiki/Carbachol" title="Carbachol">Carbachol</a></li> <li><a href="/wiki/Choline" title="Choline">Choline</a></li> <li><a href="/wiki/Cotinine" title="Cotinine">Cotinine</a></li> <li><a href="/wiki/Cytisine" title="Cytisine">Cytisine</a></li> <li><a href="/wiki/Decamethonium" title="Decamethonium">Decamethonium</a></li> <li><a href="/wiki/Desformylflustrabromine" title="Desformylflustrabromine">Desformylflustrabromine</a></li> <li><a href="/wiki/Dianicline" title="Dianicline">Dianicline</a></li> <li><a href="/wiki/Dimethylphenylpiperazinium" title="Dimethylphenylpiperazinium">Dimethylphenylpiperazinium</a></li> <li><a href="/wiki/Epibatidine" title="Epibatidine">Epibatidine</a></li> <li><a href="/wiki/Epiboxidine" title="Epiboxidine">Epiboxidine</a></li> <li><a href="/wiki/Alcohol_(drug)" title="Alcohol (drug)">Ethanol (alcohol)</a></li> <li><a href="/w/index.php?title=Ethoxysebacylcholine&action=edit&redlink=1" class="new" title="Ethoxysebacylcholine (page does not exist)">Ethoxysebacylcholine</a></li> <li><a href="/w/index.php?title=EVP-4473&action=edit&redlink=1" class="new" title="EVP-4473 (page does not exist)">EVP-4473</a></li> <li><a href="/wiki/EVP-6124" class="mw-redirect" title="EVP-6124">EVP-6124</a></li> <li><a href="/wiki/Galantamine" title="Galantamine">Galantamine</a></li> <li><a href="/wiki/GTS-21" title="GTS-21">GTS-21</a></li> <li><a href="/wiki/Ispronicline" title="Ispronicline">Ispronicline</a></li> <li><a href="/wiki/Ivermectin" title="Ivermectin">Ivermectin</a></li> <li><a href="/wiki/JNJ-39393406" title="JNJ-39393406">JNJ-39393406</a></li> <li><a href="/wiki/Levamisole" title="Levamisole">Levamisole</a></li> <li><a href="/wiki/Lobeline" title="Lobeline">Lobeline</a></li> <li><a href="/w/index.php?title=MEM-63,908&action=edit&redlink=1" class="new" title="MEM-63,908 (page does not exist)">MEM-63,908 (RG-3487)</a></li> <li><a href="/wiki/Morantel" title="Morantel">Morantel</a></li> <li><a href="/wiki/Nicotine" title="Nicotine">Nicotine</a> (<a href="/wiki/Tobacco" title="Tobacco">tobacco</a>)</li> <li><a href="/w/index.php?title=NS-1738&action=edit&redlink=1" class="new" title="NS-1738 (page does not exist)">NS-1738</a></li> <li><a href="/wiki/PHA-543,613" title="PHA-543,613">PHA-543,613</a></li> <li><a href="/w/index.php?title=PHA-709,829&action=edit&redlink=1" class="new" title="PHA-709,829 (page does not exist)">PHA-709,829</a></li> <li><a href="/wiki/PNU-120,596" title="PNU-120,596">PNU-120,596</a></li> <li><a href="/wiki/PNU-282,987" title="PNU-282,987">PNU-282,987</a></li> <li><a href="/wiki/Pozanicline" title="Pozanicline">Pozanicline</a></li> <li><a href="/wiki/Pyrantel" title="Pyrantel">Pyrantel</a></li> <li><a href="/wiki/Rivanicline" title="Rivanicline">Rivanicline</a></li> <li><a href="/wiki/RJR-2429" title="RJR-2429">RJR-2429</a></li> <li><a href="/wiki/Sazetidine_A" title="Sazetidine A">Sazetidine A</a></li> <li><a href="/wiki/SB-206553" title="SB-206553">SB-206553</a></li> <li><a href="/w/index.php?title=Sebacylcholine&action=edit&redlink=1" class="new" title="Sebacylcholine (page does not exist)">Sebacylcholine</a></li> <li><a href="/wiki/SIB-1508Y" class="mw-redirect" title="SIB-1508Y">SIB-1508Y</a></li> <li><a href="/wiki/SIB-1553A" title="SIB-1553A">SIB-1553A</a></li> <li><a href="/wiki/SSR-180,711" title="SSR-180,711">SSR-180,711</a></li> <li><a href="/w/index.php?title=Suberyldicholine&action=edit&redlink=1" class="new" title="Suberyldicholine (page does not exist)">Suberyldicholine</a></li> <li><a href="/wiki/Suxamethonium" class="mw-redirect" title="Suxamethonium">Suxamethonium (succinylcholine)</a></li> <li><a href="/wiki/Suxethonium_chloride" title="Suxethonium chloride">Suxethonium (succinyldicholine)</a></li> <li><a href="/wiki/TC-1698" title="TC-1698">TC-1698</a></li> <li><a href="/w/index.php?title=TC-1734&action=edit&redlink=1" class="new" title="TC-1734 (page does not exist)">TC-1734</a></li> <li><a href="/wiki/TC-1827" title="TC-1827">TC-1827</a></li> <li><a href="/wiki/TC-2216" title="TC-2216">TC-2216</a></li> <li><a href="/wiki/TC-5214" class="mw-redirect" title="TC-5214">TC-5214</a></li> <li><a href="/wiki/TC-5619" class="mw-redirect" title="TC-5619">TC-5619</a></li> <li><a href="/w/index.php?title=TC-6683&action=edit&redlink=1" class="new" title="TC-6683 (page does not exist)">TC-6683</a></li> <li><a href="/wiki/Tebanicline" title="Tebanicline">Tebanicline</a></li> <li><a href="/wiki/Tribendimidine" title="Tribendimidine">Tribendimidine</a></li> <li><a href="/wiki/Tropisetron" title="Tropisetron">Tropisetron</a></li> <li><a href="/wiki/UB-165" title="UB-165">UB-165</a></li> <li><a href="/wiki/Varenicline" title="Varenicline">Varenicline</a></li> <li><a href="/wiki/WAY-317,538" class="mw-redirect" title="WAY-317,538">WAY-317,538</a></li> <li><a href="/w/index.php?title=XY-4083&action=edit&redlink=1" class="new" title="XY-4083 (page does not exist)">XY-4083</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%;text-align:center;"><a href="/wiki/Receptor_antagonist" title="Receptor antagonist">Antagonists</a><br />(and <a href="/wiki/Negative_allosteric_modulators" class="mw-redirect" title="Negative allosteric modulators"><abbr title="negative allosteric modulators">NAMs</abbr></a><span class="sr-only" style="border: 0; clip: rect(0, 0, 0, 0); clip-path: polygon(0px 0px, 0px 0px, 0px 0px); height: 1px; margin: -1px; overflow: hidden; padding: 0; position: absolute; width: 1px; white-space: nowrap;">Tooltip negative allosteric modulators</span>)</th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/18-Methylaminocoronaridine" title="18-Methylaminocoronaridine">18-MAC</a></li> <li><a href="/wiki/18-Methoxycoronaridine" title="18-Methoxycoronaridine">18-MC</a></li> <li><a href="/wiki/%CE%91-Neurotoxin" title="Α-Neurotoxin">α-Neurotoxins</a> (e.g., <a href="/wiki/%CE%91-bungarotoxin" class="mw-redirect" title="Α-bungarotoxin">α-bungarotoxin</a>, <a href="/wiki/%CE%91-cobratoxin" class="mw-redirect" title="Α-cobratoxin">α-cobratoxin</a>, <a href="/wiki/%CE%91-conotoxin" class="mw-redirect" title="Α-conotoxin">α-conotoxin</a>, many others)</li> <li><a href="/w/index.php?title=ABT-126&action=edit&redlink=1" class="new" title="ABT-126 (page does not exist)">ABT-126</a></li> <li><a href="/wiki/Alcuronium" class="mw-redirect" title="Alcuronium">Alcuronium</a></li> <li><a href="/wiki/Allopregnanolone" title="Allopregnanolone">Allopregnanolone</a></li> <li><a href="/wiki/Amantadine" title="Amantadine">Amantadine</a></li> <li><a href="/w/index.php?title=Anatruxonium&action=edit&redlink=1" class="new" title="Anatruxonium (page does not exist)">Anatruxonium</a></li> <li><a href="/w/index.php?title=AQW051&action=edit&redlink=1" class="new" title="AQW051 (page does not exist)">AQW051</a></li> <li><a href="/wiki/Atracurium" class="mw-redirect" title="Atracurium">Atracurium</a></li> <li><a href="/wiki/Barbiturates" class="mw-redirect" title="Barbiturates">Barbiturates</a> (e.g., <a href="/wiki/Pentobarbital" title="Pentobarbital">pentobarbital</a>, <a href="/wiki/Sodium_thiopental" title="Sodium thiopental">sodium thiopental</a>)</li> <li><a href="/wiki/BNC-210" title="BNC-210">BNC-210</a></li> <li><a href="/wiki/Bungarotoxin" title="Bungarotoxin">Bungarotoxins</a> (e.g., <a href="/wiki/%CE%91-bungarotoxin" class="mw-redirect" title="Α-bungarotoxin">α-bungarotoxin</a>, <a href="/wiki/%CE%9A-bungarotoxin" class="mw-redirect" title="Κ-bungarotoxin">κ-bungarotoxin</a>)</li> <li><a href="/wiki/Bupropion" title="Bupropion">Bupropion</a></li> <li><a href="/wiki/BW284C51" title="BW284C51">BW284C51</a></li> <li><a href="/wiki/BW-A444" title="BW-A444">BW-A444</a></li> <li><a href="/wiki/Candocuronium_iodide" title="Candocuronium iodide">Candocuronium iodide (chandonium iodide)</a></li> <li><a href="/wiki/Chlorisondamine" title="Chlorisondamine">Chlorisondamine</a></li> <li><a href="/wiki/Cisatracurium" class="mw-redirect" title="Cisatracurium">Cisatracurium</a></li> <li><a href="/wiki/Coclaurine" title="Coclaurine">Coclaurine</a></li> <li><a href="/wiki/Coronaridine" title="Coronaridine">Coronaridine</a></li> <li><a href="/wiki/Curare" title="Curare">Curare</a></li> <li><a href="/wiki/Cyclopropane" title="Cyclopropane">Cyclopropane</a></li> <li><a href="/wiki/Dacuronium_bromide" title="Dacuronium bromide">Dacuronium bromide</a></li> <li><a href="/wiki/Decamethonium" title="Decamethonium">Decamethonium</a></li> <li><a href="/wiki/Dehydronorketamine" title="Dehydronorketamine">Dehydronorketamine</a></li> <li><a href="/wiki/Desflurane" title="Desflurane">Desflurane</a></li> <li><a href="/wiki/Dextromethorphan" title="Dextromethorphan">Dextromethorphan</a></li> <li><a href="/wiki/Dextropropoxyphene" title="Dextropropoxyphene">Dextropropoxyphene</a></li> <li><a href="/wiki/Dextrorphan" title="Dextrorphan">Dextrorphan</a></li> <li><a href="/w/index.php?title=Diadonium&action=edit&redlink=1" class="new" title="Diadonium (page does not exist)">Diadonium</a></li> <li><a href="/w/index.php?title=Dihydro-beta-erythroidine&action=edit&redlink=1" class="new" title="Dihydro-beta-erythroidine (page does not exist)">DHβE</a></li> <li><a href="/wiki/Dihydrochandonium" title="Dihydrochandonium">Dihydrochandonium</a></li> <li><a href="/wiki/Dimethyltubocurarine" class="mw-redirect" title="Dimethyltubocurarine">Dimethyltubocurarine (metocurine)</a></li> <li><a href="/wiki/Dioscorine" title="Dioscorine">Dioscorine</a></li> <li><a href="/wiki/Dipyrandium" title="Dipyrandium">Dipyrandium</a></li> <li><a href="/wiki/Dizocilpine" title="Dizocilpine">Dizocilpine (MK-801)</a></li> <li><a href="/wiki/Doxacurium" class="mw-redirect" title="Doxacurium">Doxacurium</a></li> <li><a href="/wiki/Encenicline" title="Encenicline">Encenicline</a></li> <li><a href="/wiki/Enflurane" title="Enflurane">Enflurane</a></li> <li><a href="/wiki/Erythravine" title="Erythravine">Erythravine</a></li> <li><a href="/wiki/Esketamine" title="Esketamine">Esketamine</a></li> <li><a href="/wiki/Fazadinium" class="mw-redirect" title="Fazadinium">Fazadinium</a></li> <li><a href="/wiki/Gallamine" class="mw-redirect" title="Gallamine">Gallamine</a></li> <li><a href="/wiki/Gantacurium_chloride" title="Gantacurium chloride">Gantacurium chloride</a></li> <li><a href="/wiki/Halothane" title="Halothane">Halothane</a></li> <li><a href="/wiki/Hexafluronium" class="mw-redirect" title="Hexafluronium">Hexafluronium</a></li> <li><a href="/wiki/Hexamethonium" title="Hexamethonium">Hexamethonium (benzohexonium)</a></li> <li><a href="/wiki/Hydroxybupropion" title="Hydroxybupropion">Hydroxybupropion</a></li> <li><a href="/wiki/Hydroxynorketamine" title="Hydroxynorketamine">Hydroxynorketamine</a></li> <li><a href="/wiki/Ibogaine" title="Ibogaine">Ibogaine</a></li> <li><a href="/wiki/Isoflurane" title="Isoflurane">Isoflurane</a></li> <li><a href="/wiki/Ketamine" title="Ketamine">Ketamine</a></li> <li><a href="/wiki/Kynurenic_acid" title="Kynurenic acid">Kynurenic acid</a></li> <li><a href="/wiki/Laudanosine" title="Laudanosine">Laudanosine</a></li> <li><a href="/wiki/Laudexium" class="mw-redirect" title="Laudexium">Laudexium (laudolissin)</a></li> <li><a href="/wiki/Levacetylmethadol" title="Levacetylmethadol">Levacetylmethadol</a></li> <li><a href="/wiki/Levomethadone" title="Levomethadone">Levomethadone</a></li> <li><a href="/wiki/Malouetine" title="Malouetine">Malouetine</a></li> <li><a href="/wiki/2-Methoxyethyl-18-methoxycoronaridinate" title="2-Methoxyethyl-18-methoxycoronaridinate">ME-18-MC</a></li> <li><a href="/wiki/Mecamylamine" title="Mecamylamine">Mecamylamine</a></li> <li><a href="/wiki/Memantine" title="Memantine">Memantine</a></li> <li><a href="/wiki/Methadone" title="Methadone">Methadone</a></li> <li><a href="/wiki/Methorphan" title="Methorphan">Methorphan (racemethorphan)</a></li> <li><a href="/wiki/Methyllycaconitine" title="Methyllycaconitine">Methyllycaconitine</a></li> <li><a href="/wiki/Metocurine" title="Metocurine">Metocurine</a></li> <li><a href="/wiki/Mivacurium" class="mw-redirect" title="Mivacurium">Mivacurium</a></li> <li><a href="/wiki/Morphanol" class="mw-redirect" title="Morphanol">Morphanol (racemorphan)</a></li> <li><a href="/wiki/Neramexane" title="Neramexane">Neramexane</a></li> <li><a href="/wiki/Nitrous_oxide" title="Nitrous oxide">Nitrous oxide</a></li> <li><a href="/wiki/Norketamine" title="Norketamine">Norketamine</a></li> <li><a href="/wiki/Pancuronium_bromide" title="Pancuronium bromide">Pancuronium bromide</a></li> <li><a href="/wiki/Pempidine" title="Pempidine">Pempidine</a></li> <li><a href="/wiki/Pentamine" title="Pentamine">Pentamine</a></li> <li><a href="/wiki/Pentolinium" title="Pentolinium">Pentolinium</a></li> <li><a href="/wiki/Phencyclidine" title="Phencyclidine">Phencyclidine</a></li> <li><a href="/wiki/Pipecuronium_bromide" title="Pipecuronium bromide">Pipecuronium bromide</a></li> <li><a href="/wiki/Progesterone" title="Progesterone">Progesterone</a></li> <li><a href="/wiki/Promegestone" title="Promegestone">Promegestone</a></li> <li><a href="/wiki/Radafaxine" title="Radafaxine">Radafaxine</a></li> <li><a href="/wiki/Rapacuronium_bromide" title="Rapacuronium bromide">Rapacuronium bromide</a></li> <li><a href="/wiki/Reboxetine" title="Reboxetine">Reboxetine</a></li> <li><a href="/wiki/Rocuronium_bromide" title="Rocuronium bromide">Rocuronium bromide</a></li> <li><a href="/wiki/Sevoflurane" title="Sevoflurane">Sevoflurane</a></li> <li><a href="/wiki/Stercuronium_iodide" title="Stercuronium iodide">Stercuronium iodide</a></li> <li><a href="/wiki/Surugatoxin" title="Surugatoxin">Surugatoxin</a></li> <li><a href="/wiki/Thiocolchicoside" title="Thiocolchicoside">Thiocolchicoside</a></li> <li><a href="/wiki/Threohydrobupropion" title="Threohydrobupropion">Threohydrobupropion</a></li> <li><a href="/wiki/Toxiferine" title="Toxiferine">Toxiferine</a></li> <li><a href="/wiki/Tramadol" title="Tramadol">Tramadol</a></li> <li><a href="/wiki/Trimetaphan_camsilate" title="Trimetaphan camsilate">Trimetaphan camsilate (trimethaphan camsylate)</a></li> <li><a href="/w/index.php?title=Tropeinium&action=edit&redlink=1" class="new" title="Tropeinium (page does not exist)">Tropeinium</a></li> <li><a href="/wiki/Tubocurarine" class="mw-redirect" title="Tubocurarine">Tubocurarine</a></li> <li><a href="/wiki/Vanoxerine" title="Vanoxerine">Vanoxerine</a></li> <li><a href="/wiki/Vecuronium_bromide" title="Vecuronium bromide">Vecuronium bromide</a></li> <li><a href="/wiki/Xenon" title="Xenon">Xenon</a></li></ul> </div></td></tr></tbody></table><div></div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%;text-align:center;"><a href="/wiki/Precursor_(chemistry)" title="Precursor (chemistry)">Precursors</a><br /><small>(and <a href="/wiki/Prodrug" title="Prodrug">prodrugs</a>)</small></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Acetyl-coA" class="mw-redirect" title="Acetyl-coA">Acetyl-coA</a></li> <li><a href="/wiki/Adafenoxate" title="Adafenoxate">Adafenoxate</a></li> <li><a href="/wiki/Choline" title="Choline">Choline</a> (<a href="/wiki/Lecithin" title="Lecithin">lecithin</a>)</li> <li><a href="/wiki/Citicoline" title="Citicoline">Citicoline</a></li> <li><a href="/wiki/Cyprodenate" title="Cyprodenate">Cyprodenate</a></li> <li><a href="/wiki/Dimethylethanolamine" title="Dimethylethanolamine">Dimethylethanolamine</a></li> <li><a href="/wiki/Glycerophosphocholine" class="mw-redirect" title="Glycerophosphocholine">Glycerophosphocholine</a></li> <li><a href="/wiki/Meclofenoxate" title="Meclofenoxate">Meclofenoxate (centrophenoxine)</a></li> <li><a href="/wiki/Phosphatidylcholine" title="Phosphatidylcholine">Phosphatidylcholine</a></li> <li><a href="/wiki/Phosphatidylethanolamine" title="Phosphatidylethanolamine">Phosphatidylethanolamine</a></li> <li><a href="/wiki/Phosphorylcholine" title="Phosphorylcholine">Phosphorylcholine</a></li> <li><a href="/wiki/Pirisudanol" title="Pirisudanol">Pirisudanol</a></li></ul> </div></td></tr><tr><td class="navbox-abovebelow" colspan="2"><div> <dl><dt>See also</dt> <dd><a href="/wiki/Template:Receptor_modulators" title="Template:Receptor modulators">Receptor/signaling modulators</a></dd> <dd><a href="/wiki/Template:Muscarinic_acetylcholine_receptor_modulators" title="Template:Muscarinic acetylcholine receptor modulators">Muscarinic acetylcholine receptor modulators</a></dd> <dd><a href="/wiki/Template:Acetylcholine_metabolism_and_transport_modulators" title="Template:Acetylcholine metabolism and transport modulators">Acetylcholine metabolism/transport modulators</a></dd></dl> </div></td></tr></tbody></table></div>    </div><noscript><img src="https://login.wikimedia.org/wiki/Special:CentralAutoLogin/start?type=1x1" alt="" width="1" height="1" style="border: none; position: absolute;"></noscript> <div class="printfooter" data-nosnippet="">Retrieved from "<a dir="ltr" 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