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vector-toc-level-2"> <a class="vector-toc-link" href="#Pharmacokinetics"> <div class="vector-toc-text"> <span class="vector-toc-numb">5.2</span> <span>Pharmacokinetics</span> </div> </a> <ul id="toc-Pharmacokinetics-sublist" class="vector-toc-list"> <li id="toc-Buprenorphine" class="vector-toc-list-item vector-toc-level-3"> <a class="vector-toc-link" href="#Buprenorphine"> <div class="vector-toc-text"> <span class="vector-toc-numb">5.2.1</span> <span>Buprenorphine</span> </div> </a> <ul id="toc-Buprenorphine-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Naloxone" class="vector-toc-list-item vector-toc-level-3"> <a class="vector-toc-link" href="#Naloxone"> <div class="vector-toc-text"> <span class="vector-toc-numb">5.2.2</span> <span>Naloxone</span> </div> </a> <ul id="toc-Naloxone-sublist" class="vector-toc-list"> </ul> </li> </ul> </li> </ul> </li> <li id="toc-Society_and_culture" class="vector-toc-list-item vector-toc-level-1 vector-toc-list-item-expanded"> <a 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<span>Access in the United States</span> </div> </a> <ul id="toc-Access_in_the_United_States-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Controversies" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Controversies"> <div class="vector-toc-text"> <span class="vector-toc-numb">6.3</span> <span>Controversies</span> </div> </a> <ul id="toc-Controversies-sublist" class="vector-toc-list"> </ul> </li> </ul> </li> <li id="toc-References" class="vector-toc-list-item vector-toc-level-1 vector-toc-list-item-expanded"> <a class="vector-toc-link" href="#References"> <div class="vector-toc-text"> <span class="vector-toc-numb">7</span> <span>References</span> </div> </a> <ul id="toc-References-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" 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mw-first-heading"><span class="mw-page-title-main">Buprenorphine/naloxone</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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class="interlanguage-link-target"><span>العربية</span></a></li><li class="interlanguage-link interwiki-es mw-list-item"><a href="https://es.wikipedia.org/wiki/Buprenorfina/naloxona" title="Buprenorfina/naloxona – Spanish" lang="es" hreflang="es" data-title="Buprenorfina/naloxona" data-language-autonym="Español" data-language-local-name="Spanish" class="interlanguage-link-target"><span>Español</span></a></li><li class="interlanguage-link interwiki-ja mw-list-item"><a href="https://ja.wikipedia.org/wiki/%E3%83%96%E3%83%97%E3%83%AC%E3%83%8E%E3%83%AB%E3%83%95%E3%82%A3%E3%83%B3%E3%83%BB%E3%83%8A%E3%83%AD%E3%82%AD%E3%82%BD%E3%83%B3" title="ブプレノルフィン・ナロキソン – Japanese" lang="ja" hreflang="ja" data-title="ブプレノルフィン・ナロキソン" 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-or mw-list-item"><a href="https://or.wikipedia.org/wiki/%E0%AC%AC%E0%AD%81%E0%AC%AA%E0%AD%8D%E0%AC%B0%E0%AD%87%E0%AC%A8%E0%AC%B0%E0%AD%8D%E0%AC%AB%E0%AC%BF%E0%AC%A8/%E0%AC%A8%E0%AC%BE%E0%AC%B2%E0%AD%8B%E0%AC%95%E0%AD%8D%E0%AC%B8%E0%AD%8B%E0%AC%A8" title="ବୁପ୍ରେନର୍ଫିନ/ନାଲୋକ୍ସୋନ – Odia" lang="or" hreflang="or" data-title="ବୁପ୍ରେନର୍ଫିନ/ନାଲୋକ୍ସୋନ" data-language-autonym="ଓଡ଼ିଆ" data-language-local-name="Odia" class="interlanguage-link-target"><span>ଓଡ଼ିଆ</span></a></li><li class="interlanguage-link interwiki-sv mw-list-item"><a href="https://sv.wikipedia.org/wiki/Suboxone" title="Suboxone – Swedish" lang="sv" hreflang="sv" data-title="Suboxone" data-language-autonym="Svenska" data-language-local-name="Swedish" class="interlanguage-link-target"><span>Svenska</span></a></li><li class="interlanguage-link interwiki-tr mw-list-item"><a href="https://tr.wikipedia.org/wiki/Buprenorfin/nalokson" title="Buprenorfin/nalokson – Turkish" lang="tr" hreflang="tr" data-title="Buprenorfin/nalokson" 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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">Opioid treatment</div> <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">Not to be confused with <a href="/wiki/Bupropion/naltrexone" class="mw-redirect" title="Bupropion/naltrexone">Bupropion/naltrexone</a>.</div> <p class="mw-empty-elt"> </p> <div class="shortdescription nomobile noexcerpt noprint searchaux" style="display:none">Pharmaceutical compound</div><style data-mw-deduplicate="TemplateStyles:r1257001546">.mw-parser-output .infobox-subbox{padding:0;border:none;margin:-3px;width:auto;min-width:100%;font-size:100%;clear:none;float:none;background-color:transparent}.mw-parser-output .infobox-3cols-child{margin:auto}.mw-parser-output .infobox .navbar{font-size:100%}@media screen{html.skin-theme-clientpref-night .mw-parser-output .infobox-full-data:not(.notheme)>div:not(.notheme)[style]{background:#1f1f23!important;color:#f8f9fa}}@media screen and (prefers-color-scheme:dark){html.skin-theme-clientpref-os .mw-parser-output .infobox-full-data:not(.notheme) div:not(.notheme){background:#1f1f23!important;color:#f8f9fa}}@media(min-width:640px){body.skin--responsive .mw-parser-output .infobox-table{display:table!important}body.skin--responsive .mw-parser-output .infobox-table>caption{display:table-caption!important}body.skin--responsive .mw-parser-output .infobox-table>tbody{display:table-row-group}body.skin--responsive .mw-parser-output .infobox-table tr{display:table-row!important}body.skin--responsive .mw-parser-output .infobox-table th,body.skin--responsive .mw-parser-output .infobox-table td{padding-left:inherit;padding-right:inherit}}</style><table class="infobox" style="border-spacing:2px;"><caption class="infobox-title"><span title="International nonproprietary name (INN): Buprenorphine/naloxone">Buprenorphine/naloxone</span></caption><tbody><tr><td colspan="2" class="infobox-image notheme" style="background-color: #f8f9fa;"><span typeof="mw:File"><a href="/wiki/File:Buprenorphine.svg" class="mw-file-description"><img src="//upload.wikimedia.org/wikipedia/commons/thumb/b/b0/Buprenorphine.svg/215px-Buprenorphine.svg.png" decoding="async" width="215" height="209" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/b/b0/Buprenorphine.svg/323px-Buprenorphine.svg.png 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/b/b0/Buprenorphine.svg/430px-Buprenorphine.svg.png 2x" data-file-width="580" data-file-height="565" /></a></span><div class="infobox-caption"><a href="/wiki/Buprenorphine" title="Buprenorphine">Buprenorphine</a>, an <a href="/wiki/Opioid" title="Opioid">opioid</a></div></td></tr><tr><td colspan="2" class="infobox-image notheme" style="background-color: #f8f9fa;"><span typeof="mw:File"><a href="/wiki/File:Naloxone.svg" class="mw-file-description"><img src="//upload.wikimedia.org/wikipedia/commons/thumb/2/2f/Naloxone.svg/225px-Naloxone.svg.png" decoding="async" width="225" height="187" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/2/2f/Naloxone.svg/338px-Naloxone.svg.png 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/2/2f/Naloxone.svg/450px-Naloxone.svg.png 2x" data-file-width="538" data-file-height="446" /></a></span><div class="infobox-caption"><a href="/wiki/Naloxone" title="Naloxone">Naloxone</a>, an opioid antagonist</div></td></tr><tr><th colspan="2" class="infobox-header" style="background:#ddd">Combination of</th></tr><tr><th scope="row" class="infobox-label" style="line-height:1.2em;"><a href="/wiki/Buprenorphine" title="Buprenorphine">Buprenorphine</a></th><td class="infobox-data"><a href="/wiki/Opioid_modulator" title="Opioid modulator">Opioid modulator</a></td></tr><tr><th scope="row" class="infobox-label" style="line-height:1.2em;"><a href="/wiki/Naloxone" title="Naloxone">Naloxone</a></th><td class="infobox-data"><a href="/wiki/Opioid_antagonist" title="Opioid antagonist">Opioid antagonist</a></td></tr><tr><th colspan="2" class="infobox-header" style="background:#ddd">Clinical data</th></tr><tr><th scope="row" class="infobox-label" style="line-height:1.2em;"><a href="/wiki/Drug_nomenclature#Trade_names" title="Drug nomenclature">Trade names</a></th><td class="infobox-data">Suboxone, Bunavail, Zubsolv, others<sup id="cite_ref-SAM2016_1-0" class="reference"><a href="#cite_note-SAM2016-1"><span class="cite-bracket">[</span>1<span class="cite-bracket">]</span></a></sup></td></tr><tr><th scope="row" class="infobox-label" style="line-height:1.2em;"><a href="/wiki/American_Society_of_Health-System_Pharmacists" title="American Society of Health-System Pharmacists">AHFS</a>/<a href="/wiki/Drugs.com" title="Drugs.com">Drugs.com</a></th><td class="infobox-data"><span title="www.drugs.com"><a rel="nofollow" class="external text" href="https://www.drugs.com/monograph/buprenorphine.html">Monograph</a></span></td></tr><tr><th scope="row" class="infobox-label" style="line-height:1.2em;"><a href="/wiki/Regulation_of_therapeutic_goods" title="Regulation of therapeutic goods">License data</a></th><td class="infobox-data"><style data-mw-deduplicate="TemplateStyles:r1126788409">.mw-parser-output .plainlist ol,.mw-parser-output .plainlist ul{line-height:inherit;list-style:none;margin:0;padding:0}.mw-parser-output .plainlist ol li,.mw-parser-output .plainlist ul li{margin-bottom:0}</style><div class="plainlist"> <ul><li><small><abbr class="country-name" title="United States">US</abbr></small> <a href="/wiki/DailyMed" title="DailyMed">DailyMed</a>: <span title="dailymed.nlm.nih.gov"><a rel="nofollow" class="external text" href="https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=Buprenorphine+and+naloxone">Buprenorphine and naloxone</a></span></li></ul></div> </td></tr><tr><th scope="row" class="infobox-label" style="line-height:1.2em;"><a href="/wiki/Pregnancy_category" title="Pregnancy category">Pregnancy<br />category</a></th><td class="infobox-data"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1126788409"><div class="plainlist"> <ul><li><small><abbr class="country-name" title="Australia">AU</abbr>:</small> C</li> <li class="mw-empty-elt"></li></ul> </div></td></tr><tr><th scope="row" class="infobox-label" style="line-height:1.2em;"><a href="/wiki/Route_of_administration" title="Route of administration">Routes of<br />administration</a></th><td class="infobox-data"><a href="/wiki/Sublingual" class="mw-redirect" title="Sublingual">Sublingual</a>, <a href="/wiki/Buccal_administration" title="Buccal administration">buccal</a></td></tr><tr><th scope="row" class="infobox-label" style="line-height:1.2em;"><a href="/wiki/Anatomical_Therapeutic_Chemical_Classification_System" title="Anatomical Therapeutic Chemical Classification System">ATC code</a></th><td class="infobox-data"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1126788409"><div class="plainlist"><ul><li><a href="/wiki/ATC_code_N07" title="ATC code N07">N07BC51</a> (<span title="www.whocc.no"><a rel="nofollow" class="external text" href="https://www.whocc.no/atc_ddd_index/?code=N07BC51">WHO</a></span>) </li></ul></div></td></tr><tr><th colspan="2" class="infobox-header" style="background:#ddd">Legal status</th></tr><tr><th scope="row" class="infobox-label" style="line-height:1.2em;"><a href="/wiki/Regulation_of_therapeutic_goods" title="Regulation of therapeutic goods">Legal status</a></th><td class="infobox-data"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1126788409"><div class="plainlist"> <ul><li><small><abbr class="country-name" title="Australia">AU</abbr>:</small> <a href="/wiki/Standard_for_the_Uniform_Scheduling_of_Medicines_and_Poisons#Schedule_8" title="Standard for the Uniform Scheduling of Medicines and Poisons">S8</a> (Controlled drug)</li> <li><small><abbr class="country-name" title="Canada">CA</abbr></small>: <a href="/wiki/Prescription_drug" title="Prescription drug"> ℞-only</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></li> <li><small><abbr class="country-name" title="United Kingdom">UK</abbr>:</small> <a href="/wiki/Prescription_drug" title="Prescription drug">POM</a> (Prescription only)</li> <li><small><abbr class="country-name" title="United States">US</abbr>:</small> <a href="/wiki/Controlled_Substances_Act#Schedule_III_drugs" title="Controlled Substances Act">Schedule III</a><sup id="cite_ref-Suboxone_FDA_label_3-0" class="reference"><a href="#cite_note-Suboxone_FDA_label-3"><span class="cite-bracket">[</span>3<span class="cite-bracket">]</span></a></sup></li> <li><small><abbr class="country-name" title="European Union">EU</abbr>:</small> Rx-only<sup id="cite_ref-Zubsolv_EPAR_4-0" class="reference"><a href="#cite_note-Zubsolv_EPAR-4"><span class="cite-bracket">[</span>4<span class="cite-bracket">]</span></a></sup></li></ul></div> </td></tr><tr><th colspan="2" class="infobox-header" style="background:#ddd">Identifiers</th></tr><tr><th scope="row" class="infobox-label" style="line-height:1.2em;"><a href="/wiki/CAS_Registry_Number" title="CAS Registry Number">CAS Number</a></th><td class="infobox-data"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1126788409"><div class="plainlist"><ul><li><span title="commonchemistry.cas.org"><a rel="nofollow" class="external text" href="https://commonchemistry.cas.org/detail?cas_rn=352020-56-5">352020-56-5</a></span></li></ul></div></td></tr><tr><th scope="row" class="infobox-label" style="line-height:1.2em;"><a href="/wiki/PubChem#CID" title="PubChem">PubChem</a> <span style="font-weight:normal"><abbr title="Compound ID">CID</abbr></span></th><td class="infobox-data"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1126788409"><div class="plainlist"><ul><li><span title="pubchem.ncbi.nlm.nih.gov"><a rel="nofollow" class="external text" href="https://pubchem.ncbi.nlm.nih.gov/compound/11274356">11274356</a></span></li></ul></div></td></tr><tr><th scope="row" class="infobox-label" style="line-height:1.2em;"><a href="/wiki/KEGG" title="KEGG">KEGG</a></th><td class="infobox-data"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1126788409"><div class="plainlist"><ul><li><span title="www.kegg.jp"><a rel="nofollow" class="external text" href="https://www.kegg.jp/entry/D10250">D10250</a></span></li></ul></div></td></tr><tr><th scope="row" class="infobox-label" style="line-height:1.2em;"><a href="/wiki/CompTox_Chemicals_Dashboard" title="CompTox Chemicals Dashboard">CompTox Dashboard</a> <span style="font-weight:normal">(<abbr title="U.S. Environmental Protection Agency">EPA</abbr>)</span></th><td class="infobox-data"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1126788409"><div class="plainlist"><ul><li><span title="comptox.epa.gov"><a rel="nofollow" class="external text" href="https://comptox.epa.gov/dashboard/chemical/details/DTXSID50188706">DTXSID50188706</a> <span class="mw-valign-text-top noprint" typeof="mw:File/Frameless"><a href="https://www.wikidata.org/wiki/Q25048068#P3117" title="Edit this at Wikidata"><img alt="Edit this at Wikidata" src="//upload.wikimedia.org/wikipedia/en/thumb/8/8a/OOjs_UI_icon_edit-ltr-progressive.svg/10px-OOjs_UI_icon_edit-ltr-progressive.svg.png" decoding="async" width="10" height="10" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/en/thumb/8/8a/OOjs_UI_icon_edit-ltr-progressive.svg/15px-OOjs_UI_icon_edit-ltr-progressive.svg.png 1.5x, //upload.wikimedia.org/wikipedia/en/thumb/8/8a/OOjs_UI_icon_edit-ltr-progressive.svg/20px-OOjs_UI_icon_edit-ltr-progressive.svg.png 2x" data-file-width="20" data-file-height="20" /></a></span></span></li></ul></div></td></tr></tbody></table> <p><b>Buprenorphine/naloxone</b>, sold under the brand name <b>Suboxone</b> among others, is a fixed-dose <a href="/wiki/Combination_drug" title="Combination drug">combination medication</a> that includes <a href="/wiki/Buprenorphine" title="Buprenorphine">buprenorphine</a> and <a href="/wiki/Naloxone" title="Naloxone">naloxone</a>.<sup id="cite_ref-Suboxone_FDA_label_3-1" class="reference"><a href="#cite_note-Suboxone_FDA_label-3"><span class="cite-bracket">[</span>3<span class="cite-bracket">]</span></a></sup> It is used to treat <a href="/wiki/Opioid_use_disorder" title="Opioid use disorder">opioid use disorder</a>, and reduces the mortality of opioid use disorder by 50% (by reducing the risk of overdose on <a href="/wiki/Full_agonist" class="mw-redirect" title="Full agonist">full-agonist</a> opioids such as <a href="/wiki/Heroin" title="Heroin">heroin</a> or <a href="/wiki/Fentanyl" title="Fentanyl">fentanyl</a>).<sup id="cite_ref-Suboxone_FDA_label_3-2" class="reference"><a href="#cite_note-Suboxone_FDA_label-3"><span class="cite-bracket">[</span>3<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-Fish2008_5-0" class="reference"><a href="#cite_note-Fish2008-5"><span class="cite-bracket">[</span>5<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-6" class="reference"><a href="#cite_note-6"><span class="cite-bracket">[</span>6<span class="cite-bracket">]</span></a></sup> It relieves cravings to use and withdrawal symptoms.<sup id="cite_ref-Sri2017_7-0" class="reference"><a href="#cite_note-Sri2017-7"><span class="cite-bracket">[</span>7<span class="cite-bracket">]</span></a></sup> Buprenorphine/naloxone is available for use in two different forms, <a href="/wiki/Sublingual" class="mw-redirect" title="Sublingual">under the tongue</a> or <a href="/wiki/Buccal_administration" title="Buccal administration">in the cheek</a>.<sup id="cite_ref-SAM2016_1-1" class="reference"><a href="#cite_note-SAM2016-1"><span class="cite-bracket">[</span>1<span class="cite-bracket">]</span></a></sup> </p><p>Side effects may include respiratory depression (decreased breathing), <a href="/wiki/Miosis" title="Miosis">small pupils</a>, sleepiness, and <a href="/wiki/Hypotension" title="Hypotension">low blood pressure</a>.<sup id="cite_ref-Suboxone_FDA_label_3-3" class="reference"><a href="#cite_note-Suboxone_FDA_label-3"><span class="cite-bracket">[</span>3<span class="cite-bracket">]</span></a></sup> The risk of <a href="/wiki/Overdose" class="mw-redirect" title="Overdose">overdose</a> with buprenorphine/naloxone (unless combined with other sedating substances) is exceedingly low, and lower than with <a href="/wiki/Methadone" title="Methadone">methadone</a>,<sup id="cite_ref-Sri2017_7-1" class="reference"><a href="#cite_note-Sri2017-7"><span class="cite-bracket">[</span>7<span class="cite-bracket">]</span></a></sup> but people are more likely to stop treatment on buprenorphine/naloxone than methadone.<sup id="cite_ref-Sri2017_7-2" class="reference"><a href="#cite_note-Sri2017-7"><span class="cite-bracket">[</span>7<span class="cite-bracket">]</span></a></sup> Buprenorphine (like methadone) is a treatment option during pregnancy. </p><p>At lower doses, buprenorphine results in the usual <a href="/wiki/Opioid" title="Opioid">opioid</a> effects; high doses beyond a certain level do not result in greater effects.<sup id="cite_ref-Can2017_8-0" class="reference"><a href="#cite_note-Can2017-8"><span class="cite-bracket">[</span>8<span class="cite-bracket">]</span></a></sup> This is believed to result in a lower risk of overdose than some other opioids.<sup id="cite_ref-Can2017_8-1" class="reference"><a href="#cite_note-Can2017-8"><span class="cite-bracket">[</span>8<span class="cite-bracket">]</span></a></sup> Naloxone is an <a href="/wiki/Opioid_antagonist" title="Opioid antagonist">opioid antagonist</a> that competes with and blocks the effect of other opioids (including buprenorphine) if given by injection.<sup id="cite_ref-Suboxone_FDA_label_3-4" class="reference"><a href="#cite_note-Suboxone_FDA_label-3"><span class="cite-bracket">[</span>3<span class="cite-bracket">]</span></a></sup> Naloxone is poorly absorbed when taken by mouth and is added to decrease the risk that people will misuse the medication by injection.<sup id="cite_ref-SAM2016_1-2" class="reference"><a href="#cite_note-SAM2016-1"><span class="cite-bracket">[</span>1<span class="cite-bracket">]</span></a></sup> Misuse by injection or <a href="/wiki/Intranasal" class="mw-redirect" title="Intranasal">use in the nose</a> still occurs, and more recently the efficacy of naloxone in preventing misuse by injection has been brought into question and preparations including naloxone could even be less safe than preparations containing solely buprenorphine.<sup id="cite_ref-Suboxone_FDA_label_3-5" class="reference"><a href="#cite_note-Suboxone_FDA_label-3"><span class="cite-bracket">[</span>3<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-reconsidering2020_9-0" class="reference"><a href="#cite_note-reconsidering2020-9"><span class="cite-bracket">[</span>9<span class="cite-bracket">]</span></a></sup> Rates of misuse in the U.S. appear to be lower than with other opioids.<sup id="cite_ref-Yok2011_10-0" class="reference"><a href="#cite_note-Yok2011-10"><span class="cite-bracket">[</span>10<span class="cite-bracket">]</span></a></sup> </p><p>The combination formulation was approved for medical use in the U.S. in 2002,<sup id="cite_ref-Suboxone_FDA_label_3-6" class="reference"><a href="#cite_note-Suboxone_FDA_label-3"><span class="cite-bracket">[</span>3<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-Yok2011_10-1" class="reference"><a href="#cite_note-Yok2011-10"><span class="cite-bracket">[</span>10<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-11" class="reference"><a href="#cite_note-11"><span class="cite-bracket">[</span>11<span class="cite-bracket">]</span></a></sup> and in the European Union in 2017.<sup id="cite_ref-Zubsolv_EPAR_4-1" class="reference"><a href="#cite_note-Zubsolv_EPAR-4"><span class="cite-bracket">[</span>4<span class="cite-bracket">]</span></a></sup> A <a href="/wiki/Generic_medication" class="mw-redirect" title="Generic medication">generic version</a> was approved in the U.S. in 2018.<sup id="cite_ref-12" class="reference"><a href="#cite_note-12"><span class="cite-bracket">[</span>12<span class="cite-bracket">]</span></a></sup> In 2019, it was the 272nd most commonly prescribed medication in the U.S., with more than 1<span class="nowrap"> </span>million prescriptions.<sup id="cite_ref-13" class="reference"><a href="#cite_note-13"><span class="cite-bracket">[</span>13<span class="cite-bracket">]</span></a></sup> </p> <meta property="mw:PageProp/toc" /> <div class="mw-heading mw-heading2"><h2 id="Medical_uses">Medical uses</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Buprenorphine/naloxone&action=edit&section=1" title="Edit section: Medical uses"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <figure class="mw-default-size" typeof="mw:File/Thumb"><a href="/wiki/File:Suboxone.jpg" class="mw-file-description"><img src="//upload.wikimedia.org/wikipedia/commons/thumb/1/14/Suboxone.jpg/220px-Suboxone.jpg" decoding="async" width="220" height="127" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/1/14/Suboxone.jpg/330px-Suboxone.jpg 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/1/14/Suboxone.jpg/440px-Suboxone.jpg 2x" data-file-width="1417" data-file-height="818" /></a><figcaption>Sublingual tablets</figcaption></figure> <figure class="mw-default-size" typeof="mw:File/Thumb"><a href="/wiki/File:Suboxone_SL_Tabs.jpg" class="mw-file-description"><img src="//upload.wikimedia.org/wikipedia/commons/thumb/4/4f/Suboxone_SL_Tabs.jpg/220px-Suboxone_SL_Tabs.jpg" decoding="async" width="220" height="165" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/4/4f/Suboxone_SL_Tabs.jpg/330px-Suboxone_SL_Tabs.jpg 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/4/4f/Suboxone_SL_Tabs.jpg/440px-Suboxone_SL_Tabs.jpg 2x" data-file-width="2048" data-file-height="1536" /></a><figcaption>Film (package)</figcaption></figure> <p>Buprenorphine/naloxone is used for the treatment of <a href="/wiki/Opioid_use_disorder" title="Opioid use disorder">opioid use disorder</a>.<sup id="cite_ref-NAMI_14-0" class="reference"><a href="#cite_note-NAMI-14"><span class="cite-bracket">[</span>14<span class="cite-bracket">]</span></a></sup> Long-term outcomes are generally better with use of buprenorphine/naloxone than attempts at stopping opioid use altogether.<sup id="cite_ref-Sri2017_7-3" class="reference"><a href="#cite_note-Sri2017-7"><span class="cite-bracket">[</span>7<span class="cite-bracket">]</span></a></sup> This includes a lower risk of overdose with medication use.<sup id="cite_ref-Sri2017_7-4" class="reference"><a href="#cite_note-Sri2017-7"><span class="cite-bracket">[</span>7<span class="cite-bracket">]</span></a></sup> Due to the high binding affinity and low activation at the opioid receptor, cravings and withdrawal for opioids are decreased while preventing a person from getting high and relapsing on another opioid. The combination of the two medications is preferred over buprenorphine alone for maintenance treatment due to the presence of naloxone in the formulation, which is believed to help discourage intravenous use.<sup id="cite_ref-NAMI_14-1" class="reference"><a href="#cite_note-NAMI-14"><span class="cite-bracket">[</span>14<span class="cite-bracket">]</span></a></sup> However, the belief that the addition of naloxone provides this benefit has been called into question, and posters on drug-related online forums have stated that they were able to attain a high by injecting preparations of buprenorphine despite being combined with naloxone.<sup id="cite_ref-reconsidering2020_9-1" class="reference"><a href="#cite_note-reconsidering2020-9"><span class="cite-bracket">[</span>9<span class="cite-bracket">]</span></a></sup> </p><p>Buprenorphine/naloxone is effective for treating opioid dependence and serves as a recommended first-line medication according to the U.S. <a href="/wiki/National_Institute_on_Drug_Abuse" title="National Institute on Drug Abuse">National Institute on Drug Abuse</a>.<sup id="cite_ref-Yok2011_10-2" class="reference"><a href="#cite_note-Yok2011-10"><span class="cite-bracket">[</span>10<span class="cite-bracket">]</span></a></sup> The medication is an effective maintenance therapy for opioid dependence and has generally similar efficacy to methadone. Both <span class="nowrap">treatments<span style="white-space: nowrap;"> </span>—</span><span style="white-space: nowrap;"> </span>buprenorphine/naloxone and <span class="nowrap">methadone<span style="white-space: nowrap;"> </span>—</span><span style="white-space: nowrap;"> </span>are substantially more effective than abstinence-based treatment.<sup id="cite_ref-Sri2017_7-5" class="reference"><a href="#cite_note-Sri2017-7"><span class="cite-bracket">[</span>7<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-:2_15-0" class="reference"><a href="#cite_note-:2-15"><span class="cite-bracket">[</span>15<span class="cite-bracket">]</span></a></sup> As of October 2023 prescribers no longer need a <a href="/wiki/Drug_Addiction_Treatment_Act" title="Drug Addiction Treatment Act">Drug Addiction Treatment Act</a> (DATA 2000) waiver to prescribe buprenorphine/nalaxone for <a href="/wiki/Opioid_dependence" class="mw-redirect" title="Opioid dependence">opioid dependence</a>.<sup id="cite_ref-16" class="reference"><a href="#cite_note-16"><span class="cite-bracket">[</span>16<span class="cite-bracket">]</span></a></sup> All practitioners who have a current DEA registration that includes Schedule III authority, may now prescribe buprenorphine for opioid use disorder in their practice if permitted by applicable state law. The <a href="/wiki/Substance_Abuse_and_Mental_Health_Services_Administration" title="Substance Abuse and Mental Health Services Administration">Substance Abuse and Mental Health Services Administration</a> encourages practitioners to treat patients within their practices who require treatment for a substance use disorder. Because it may now be prescribed much more readily out of an office setting (as opposed to methadone, which requires <a href="/wiki/Methadone_clinic" title="Methadone clinic">specialized centers</a>), buprenorphine/naloxone allows people more access to this medication and more freedom of administration. It also thus comes with more risks in this vulnerable population. Buprenorphine/naloxone may be recommended for socially stable people who use opioids who cannot retrieve medications from a center daily, who have another condition requiring regular primary care visits, or who have jobs or daily lives that require they maintain all their faculties and cannot take a sedating medication.<sup id="cite_ref-Sri2017_7-6" class="reference"><a href="#cite_note-Sri2017-7"><span class="cite-bracket">[</span>7<span class="cite-bracket">]</span></a></sup> Buprenorphine/naloxone is also recommended over methadone for people at high risk of methadone toxicity, such as the elderly, those taking high doses of <a href="/wiki/Benzodiazepine" title="Benzodiazepine">benzodiazepines</a> or other sedating substances, concomitant <a href="/wiki/Alcohol_use_disorder" class="mw-redirect" title="Alcohol use disorder">alcohol use disorder</a>, those with a lower level of opioid tolerance, and those at high risk of <a href="/wiki/Drug-induced_QT_prolongation" title="Drug-induced QT prolongation">prolonged QT interval</a>. It is also helpful to use the medication in combination with <a href="/wiki/Psychosocial" title="Psychosocial">psychosocial</a> support and counseling.<sup id="cite_ref-Suboxone_FDA_label_3-7" class="reference"><a href="#cite_note-Suboxone_FDA_label-3"><span class="cite-bracket">[</span>3<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-AC_17-0" class="reference"><a href="#cite_note-AC-17"><span class="cite-bracket">[</span>17<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading3"><h3 id="Available_forms">Available forms</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Buprenorphine/naloxone&action=edit&section=2" title="Edit section: Available forms"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>Buprenorphine/naloxone is available in sublingual formulations (that is, products that are dissolved under the tongue). There is no evidence that the tablet formulation is easier to divert and use in ways other than intended by the prescriber compared to the film formulation, or that the tablet formulation has a higher risk for accidental ingestion by children.<sup id="cite_ref-DOJ_Indivior_18-0" class="reference"><a href="#cite_note-DOJ_Indivior-18"><span class="cite-bracket">[</span>18<span class="cite-bracket">]</span></a></sup> There are various <a href="/wiki/Pharmacokinetic" class="mw-redirect" title="Pharmacokinetic">pharmacokinetic</a> differences between sublingual formulations.<sup id="cite_ref-Coe_et_al_2019_19-0" class="reference"><a href="#cite_note-Coe_et_al_2019-19"><span class="cite-bracket">[</span>19<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading2"><h2 id="Contraindications">Contraindications</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Buprenorphine/naloxone&action=edit&section=3" title="Edit section: Contraindications"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>Contraindications are severe <a href="/wiki/Respiratory_insufficiency" class="mw-redirect" title="Respiratory insufficiency">respiratory</a> or <a href="/wiki/Liver_impairment" class="mw-redirect" title="Liver impairment">liver impairment</a> and acute <a href="/wiki/Alcoholism" title="Alcoholism">alcoholism</a>.<sup id="cite_ref-AC_17-1" class="reference"><a href="#cite_note-AC-17"><span class="cite-bracket">[</span>17<span class="cite-bracket">]</span></a></sup> There are limited accounts of cross-reactivity with opioids, but there is a possibility.<sup id="cite_ref-20" class="reference"><a href="#cite_note-20"><span class="cite-bracket">[</span>20<span class="cite-bracket">]</span></a></sup> Serious <a href="/wiki/Central_nervous_system" title="Central nervous system">central nervous system</a> (CNS) and <a href="/wiki/Respiratory_depression" class="mw-redirect" title="Respiratory depression">respiratory depression</a> may also occur with concurrent use of <a href="/wiki/Central_depressant" class="mw-redirect" title="Central depressant">CNS depressants</a>, ingesting <a href="/wiki/Alcohol_(drug)" title="Alcohol (drug)">alcohol</a>, or other CNS-depressing factors while on buprenorphine/naloxone. </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=Buprenorphine/naloxone&action=edit&section=4" title="Edit section: Adverse effects"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>Side effects are similar to those of buprenorphine and other opioids.<sup id="cite_ref-AC_17-2" class="reference"><a href="#cite_note-AC-17"><span class="cite-bracket">[</span>17<span class="cite-bracket">]</span></a></sup> In addition, naloxone can induce withdrawal symptoms in people who are chemically dependent on opioids.<sup id="cite_ref-AC_17-3" class="reference"><a href="#cite_note-AC-17"><span class="cite-bracket">[</span>17<span class="cite-bracket">]</span></a></sup> The most common side effects (in order of most to least common) of sublingual tablets include <a href="/wiki/Headache" title="Headache">headaches</a>, <a href="/wiki/Opioid_withdrawal" title="Opioid withdrawal">opioid withdrawal</a> syndrome, pain, nausea, increased sweating, and <a href="/wiki/Insomnia" title="Insomnia">difficulty sleeping</a>.<sup id="cite_ref-21" class="reference"><a href="#cite_note-21"><span class="cite-bracket">[</span>21<span class="cite-bracket">]</span></a></sup> The most common side effects seen in film formulations are <a href="/wiki/Glossodynia" class="mw-redirect" title="Glossodynia">tongue pain</a>, decreased sensation and redness in the mouth, headache, nausea, vomiting, <a href="/wiki/Hyperhidrosis" title="Hyperhidrosis">excessive sweating</a>, <a href="/wiki/Constipation" title="Constipation">constipation</a>, signs and symptoms of opioid withdrawal, sleeping difficulties, pain, and swelling of the extremities.<sup id="cite_ref-Suboxone_FDA_label_3-8" class="reference"><a href="#cite_note-Suboxone_FDA_label-3"><span class="cite-bracket">[</span>3<span class="cite-bracket">]</span></a></sup> Post-approval, the most frequently reported side effects of buprenorphine/naloxone in sublingual strip form (i.e. Suboxone strips) are <a href="/wiki/Peripheral_edema" title="Peripheral edema">peripheral edema</a>, <a href="/wiki/Stomatitis" title="Stomatitis">stomatitis</a>, <a href="/wiki/Glossitis" title="Glossitis">glossitis</a>, blistering of the mouth, and <a href="/wiki/Mouth_ulcer" title="Mouth ulcer">mouth ulcers</a> (mouth sores).<sup id="cite_ref-suboxoneprescribinginfo_22-0" class="reference"><a href="#cite_note-suboxoneprescribinginfo-22"><span class="cite-bracket">[</span>22<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-optum_23-0" class="reference"><a href="#cite_note-optum-23"><span class="cite-bracket">[</span>23<span class="cite-bracket">]</span></a></sup> Use of buprenorphine/naloxone may also increase the risk of developing certain dental problems (including <a href="/wiki/Tooth_decay" title="Tooth decay">tooth decay</a> and tooth loss).<sup id="cite_ref-pmid36511932_24-0" class="reference"><a href="#cite_note-pmid36511932-24"><span class="cite-bracket">[</span>24<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-pmid37584264_25-0" class="reference"><a href="#cite_note-pmid37584264-25"><span class="cite-bracket">[</span>25<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-FDA_2022_26-0" class="reference"><a href="#cite_note-FDA_2022-26"><span class="cite-bracket">[</span>26<span class="cite-bracket">]</span></a></sup> </p><p>Buprenorphine/naloxone has a milder side effect profile than methadone and limited respiratory effects, due to both agonist/antagonist effects. But buprenorphine/naloxone may be less safe than methadone in people with stable liver disease since it can elevate liver enzymes.<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> </p> <div class="mw-heading mw-heading3"><h3 id="Dependence_and_withdrawal">Dependence and withdrawal</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Buprenorphine/naloxone&action=edit&section=5" title="Edit section: Dependence and withdrawal"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1236090951"><div role="note" class="hatnote navigation-not-searchable">Further information: <a href="/wiki/Opioid_withdrawal" title="Opioid withdrawal">Opioid withdrawal</a></div> <p>When taken in excess, buprenorphine/naloxone can produce dysphoric symptoms for non-opioid-dependent/tolerant people because buprenorphine is a partial opioid agonist. The sublingual formulation of the buprenorphine/naloxone combination was designed to reduce the potential to inject the medication in comparison to buprenorphine alone. If the combination is taken sublingually, as directed, the addition of naloxone does not diminish buprenorphine's effects. When an opioid-dependent person dissolves and injects a combination sublingual tablet, it is believed that a withdrawal effect may be triggered because of naloxone's high parenteral bioavailability.<sup id="cite_ref-:1_28-0" class="reference"><a href="#cite_note-:1-28"><span class="cite-bracket">[</span>28<span class="cite-bracket">]</span></a></sup> However, the efficacy of naloxone in preventing misuse by injection has more recently been brought into question and preparations including naloxone could even be less safe than preparations containing solely buprenorphine.<sup id="cite_ref-reconsidering2020_9-2" class="reference"><a href="#cite_note-reconsidering2020-9"><span class="cite-bracket">[</span>9<span class="cite-bracket">]</span></a></sup> While this mechanism may act to deter intravenous injection, the Suboxone formulation can still produce an opioid agonist "high" if used sublingually by non-dependent persons, leading to opioid dependence.<sup id="cite_ref-:1_28-1" class="reference"><a href="#cite_note-:1-28"><span class="cite-bracket">[</span>28<span class="cite-bracket">]</span></a></sup><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> </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=Buprenorphine/naloxone&action=edit&section=6" title="Edit section: Interactions"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>Buprenorphine's sedating/narcotic effect is increased by other sedating substances, such as other opioids, benzodiazepines, first-generation <a href="/wiki/Antihistamines" class="mw-redirect" title="Antihistamines">antihistamines</a>, <a href="/wiki/Alcohol_(drug)" title="Alcohol (drug)">alcohol</a>, and <a href="/wiki/Antipsychotic" title="Antipsychotic">antipsychotics</a>. Opioids and especially benzodiazepines also increase the risk of potentially lethal <a href="/wiki/Respiratory_depression" class="mw-redirect" title="Respiratory depression">respiratory depression</a>.<sup id="cite_ref-AC_17-4" class="reference"><a href="#cite_note-AC-17"><span class="cite-bracket">[</span>17<span class="cite-bracket">]</span></a></sup> </p><p>Strong inhibitors of the liver enzyme <a href="/wiki/CYP3A4" title="CYP3A4">CYP3A4</a>, such as <a href="/wiki/Ketoconazole" title="Ketoconazole">ketoconazole</a>, moderately increase buprenorphine concentrations; CYP3A4 inducers can theoretically decrease concentrations of buprenorphine.<sup id="cite_ref-Suboxone_FDA_label_3-9" class="reference"><a href="#cite_note-Suboxone_FDA_label-3"><span class="cite-bracket">[</span>3<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-AC_17-5" class="reference"><a href="#cite_note-AC-17"><span class="cite-bracket">[</span>17<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading2"><h2 id="Pharmacology">Pharmacology</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Buprenorphine/naloxone&action=edit&section=7" title="Edit section: Pharmacology"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <figure class="mw-default-size" typeof="mw:File/Thumb"><a href="/wiki/File:Buprenorphine-naloxone_action_at_opioid_receptor.png" class="mw-file-description"><img src="//upload.wikimedia.org/wikipedia/commons/thumb/1/14/Buprenorphine-naloxone_action_at_opioid_receptor.png/290px-Buprenorphine-naloxone_action_at_opioid_receptor.png" decoding="async" width="290" height="387" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/1/14/Buprenorphine-naloxone_action_at_opioid_receptor.png/435px-Buprenorphine-naloxone_action_at_opioid_receptor.png 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/1/14/Buprenorphine-naloxone_action_at_opioid_receptor.png/580px-Buprenorphine-naloxone_action_at_opioid_receptor.png 2x" data-file-width="720" data-file-height="960" /></a><figcaption>A theoretical model of activity: buprenorphine/naloxone at opioid receptor when taken sublingually (top) versus when injected intravenously (bottom).</figcaption></figure> <figure class="mw-default-size" typeof="mw:File/Thumb"><a href="/wiki/File:Buprenorphine_is_a_Partial_Agonist_at_the_%CE%BC-Opioid_Receptor.png" class="mw-file-description"><img src="//upload.wikimedia.org/wikipedia/commons/thumb/e/e5/Buprenorphine_is_a_Partial_Agonist_at_the_%CE%BC-Opioid_Receptor.png/220px-Buprenorphine_is_a_Partial_Agonist_at_the_%CE%BC-Opioid_Receptor.png" decoding="async" width="220" height="184" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/e/e5/Buprenorphine_is_a_Partial_Agonist_at_the_%CE%BC-Opioid_Receptor.png/330px-Buprenorphine_is_a_Partial_Agonist_at_the_%CE%BC-Opioid_Receptor.png 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/e/e5/Buprenorphine_is_a_Partial_Agonist_at_the_%CE%BC-Opioid_Receptor.png/440px-Buprenorphine_is_a_Partial_Agonist_at_the_%CE%BC-Opioid_Receptor.png 2x" data-file-width="1345" data-file-height="1125" /></a><figcaption>Buprenorphine as a partial agonist: Buprenorphine cannot fully activate the μ-opioid receptor even when the dose is escalated. This is demonstrated as a plateau in the concentration-response curve. Opioids like morphine (natural) or leu-enkephalin (endogenous in the body) produce a greater maximum response. Tramadol is a partial agonist with intermediate activity between buprenorphine and full agonists. A full description of buprenorphine with naloxone pharmacology can be found at <a rel="nofollow" class="external free" href="https://www.youtube.com/watch?v=_y8DGjkP1so">https://www.youtube.com/watch?v=_y8DGjkP1so</a></figcaption></figure> <div class="mw-heading mw-heading3"><h3 id="Mechanism_of_action">Mechanism of action</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Buprenorphine/naloxone&action=edit&section=8" title="Edit section: Mechanism of action"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>Buprenorphine binds strongly to <a href="/wiki/Opioid_receptor" title="Opioid receptor">opioid receptors</a> and acts as a <a href="/wiki/Analgesic" title="Analgesic">pain-reducing medication</a> in the <a href="/wiki/Central_nervous_system" title="Central nervous system">central nervous system</a> (CNS). It binds to the <a href="/wiki/%CE%9C-opioid_receptor" title="Μ-opioid receptor">μ-opioid receptor</a> with high affinity, which produces analgesic effects in the CNS. It is a partial μ-opioid receptor agonist and a weak <a href="/wiki/%CE%9A-opioid_receptor" title="Κ-opioid receptor">κ-opioid receptor</a> antagonist. As a <a href="/wiki/Partial_agonist" title="Partial agonist">partial agonist</a>, buprenorphine binds and activates the opioid receptors, but has only partial <a href="/wiki/Intrinsic_activity" title="Intrinsic activity">efficacy</a> at the receptor relative to a full agonist, even at maximal receptor occupancy. It is thus well-suited to treat opioid dependence, as it produces milder effects on the opioid receptor with lower dependence and habit-forming potential. </p><p>Naloxone is a pure opioid antagonist that competes with opioid molecules in the CNS and prevents them from binding to the opioid receptors.<sup id="cite_ref-:2_15-1" class="reference"><a href="#cite_note-:2-15"><span class="cite-bracket">[</span>15<span class="cite-bracket">]</span></a></sup> Naloxone's <a href="/wiki/Binding_affinity" class="mw-redirect" title="Binding affinity">binding affinity</a> is highest for the μ-opioid receptor, then the <a href="/wiki/%CE%94-opioid_receptor" title="Δ-opioid receptor">δ-opioid receptor</a>, and lowest for the κ-opioid receptor.<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> Naloxone has poor <a href="/wiki/Bioavailability" title="Bioavailability">bioavailability</a>, and is rapidly inactivated following oral administration.<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> When injected, it exerts its full effects. </p><p>The principle behind its function as a deterrent is as follows: when taken sublingually as prescribed, buprenorphine's effects at the opioid receptor dominate, while naloxone's effects are negligible due to the low oral absorption. But when someone attempts to misuse the medication via either injection or inhalation, the naloxone is intended to act as an antagonist and either reduce the opioid's euphoric effects or even precipitate withdrawal in those dependent on opioids.<sup id="cite_ref-:2_15-2" class="reference"><a href="#cite_note-:2-15"><span class="cite-bracket">[</span>15<span class="cite-bracket">]</span></a></sup> This helps reduce the potential for deviating from the prescriber's intended use relative to buprenorphine, though it does not eradicate it.<sup id="cite_ref-:4_32-0" class="reference"><a href="#cite_note-:4-32"><span class="cite-bracket">[</span>32<span class="cite-bracket">]</span></a></sup> One reason that naloxone might have limited efficacy as an abuse-deterrent is that buprenorphine binds more tightly to the <a href="/wiki/%CE%9C-opioid_receptor" title="Μ-opioid receptor">mu-opioid receptor</a> than naloxone.<sup id="cite_ref-:4_32-1" class="reference"><a href="#cite_note-:4-32"><span class="cite-bracket">[</span>32<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading3"><h3 id="Pharmacokinetics">Pharmacokinetics</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Buprenorphine/naloxone&action=edit&section=9" title="Edit section: Pharmacokinetics"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>There are small differences in the pharmacokinetics between different sublingual buprenorphine/naloxone products.<sup id="cite_ref-Coe_et_al_2019_19-1" class="reference"><a href="#cite_note-Coe_et_al_2019-19"><span class="cite-bracket">[</span>19<span class="cite-bracket">]</span></a></sup> These differences may require changes in dose when a person switches from one product to another.<sup id="cite_ref-Coe_et_al_2019_19-2" class="reference"><a href="#cite_note-Coe_et_al_2019-19"><span class="cite-bracket">[</span>19<span class="cite-bracket">]</span></a></sup> The buprenorphine/naloxone sublingual film (e.g. trade name Suboxone) achieves higher buprenorphine <a href="/wiki/Cmax_(pharmacology)" title="Cmax (pharmacology)">maximum plasma concentrations</a> (C<sub>max</sub>) and <a href="/wiki/Area_under_the_curve_(pharmacokinetics)" title="Area under the curve (pharmacokinetics)">area under the curve</a> (AUC, a measure of total drug exposure) than the original buprenorphine/naloxone sublingual tablets at equal doses.<sup id="cite_ref-Coe_et_al_2019_19-3" class="reference"><a href="#cite_note-Coe_et_al_2019-19"><span class="cite-bracket">[</span>19<span class="cite-bracket">]</span></a></sup> For example, at a buprenorphine/naloxone dose of 8 mg/2 mg, the buprenorphine C<sub>max</sub> after a single dose of the original tablet formulation is around 3 ng/mL whereas that of the 8 mg/2 mg film formulation is around 3.55 ng/mL.<sup id="cite_ref-Coe_et_al_2019_19-4" class="reference"><a href="#cite_note-Coe_et_al_2019-19"><span class="cite-bracket">[</span>19<span class="cite-bracket">]</span></a></sup> The Zubsolv trade name sublingual tablets have higher buprenorphine <a href="/wiki/Bioavailability" title="Bioavailability">bioavailability</a> than the original sublingual tablets, while the Bunavail trade name buccal films have the highest bioavailability.<sup id="cite_ref-Coe_et_al_2019_19-5" class="reference"><a href="#cite_note-Coe_et_al_2019-19"><span class="cite-bracket">[</span>19<span class="cite-bracket">]</span></a></sup> For example, a single dose of Bunavail 4.2 mg/0.7 mg achieves a C<sub>max</sub> around 3.41 ng/mL.<sup id="cite_ref-Coe_et_al_2019_19-6" class="reference"><a href="#cite_note-Coe_et_al_2019-19"><span class="cite-bracket">[</span>19<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading4"><h4 id="Buprenorphine">Buprenorphine</h4><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Buprenorphine/naloxone&action=edit&section=10" title="Edit section: Buprenorphine"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1236090951"><div role="note" class="hatnote navigation-not-searchable">Main article: <a href="/wiki/Buprenorphine#Pharmacokinetics" title="Buprenorphine">Buprenorphine § Pharmacokinetics</a></div> <p>Buprenorphine is <a href="/wiki/Metabolism" title="Metabolism">metabolized</a> by the <a href="/wiki/Liver" title="Liver">liver</a>, primarily via the <a href="/wiki/Cytochrome_P450_oxidase" class="mw-redirect" title="Cytochrome P450 oxidase">cytochrome P450</a> (CYP) <a href="/wiki/Isozyme" title="Isozyme">isozyme</a> <a href="/wiki/CYP3A4" title="CYP3A4">CYP3A4</a>, into <a href="/wiki/Norbuprenorphine" title="Norbuprenorphine">norbuprenorphine</a>. The <a href="/wiki/Glucuronidation" title="Glucuronidation">glucuronidation</a> of buprenorphine is primarily carried out by the UDP-glucuronosyltransferases (UGTs) <a href="/wiki/UGT1A1" class="mw-redirect" title="UGT1A1">UGT1A1</a> and <a href="/wiki/UGT2B7" title="UGT2B7">UGT2B7</a>, while norbuprenorphine is glucuronidated by <a href="/wiki/UGT1A1" class="mw-redirect" title="UGT1A1">UGT1A1</a> and <a href="/wiki/UGT1A3" title="UGT1A3">UGT1A3</a>. These glucuronides are then <a href="/wiki/Elimination_(pharmacology)" title="Elimination (pharmacology)">eliminated</a> mainly through <a href="/wiki/Excretion" title="Excretion">excretion</a> into <a href="/wiki/Bile" title="Bile">bile</a>. The <a href="/wiki/Elimination_half-life" class="mw-redirect" title="Elimination half-life">elimination half-life</a> of buprenorphine is 20 to 73 hours (mean 37 hours). Due to the mainly hepatic elimination, there is no risk of accumulation in people with <a href="/wiki/Renal_impairment" class="mw-redirect" title="Renal impairment">kidney problems</a>.<sup id="cite_ref-33" class="reference"><a href="#cite_note-33"><span class="cite-bracket">[</span>33<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading4"><h4 id="Naloxone">Naloxone</h4><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Buprenorphine/naloxone&action=edit&section=11" title="Edit section: Naloxone"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1236090951"><div role="note" class="hatnote navigation-not-searchable">Main article: <a href="/wiki/Naloxone#Pharmacokinetics" title="Naloxone">Naloxone § Pharmacokinetics</a></div> <p>Naloxone is extensively inactivated by <a href="/wiki/First-pass_metabolism" class="mw-redirect" title="First-pass metabolism">first-pass metabolism</a> in the liver, meaning that the use of buprenorphine/naloxone as prescribed should not lead to active naloxone in the blood (which, as an opioid antagonist, would reverse the effect of buprenorphine or other opioids). </p> <div class="mw-heading mw-heading2"><h2 id="Society_and_culture">Society and culture</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Buprenorphine/naloxone&action=edit&section=12" title="Edit section: Society and culture"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <div class="mw-heading mw-heading3"><h3 id="Cost">Cost</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Buprenorphine/naloxone&action=edit&section=13" title="Edit section: Cost"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>While the cost of the medication buprenorphine/naloxone is greater than buprenorphine alone, one analysis predicted the overall costs would be less in the United States due to a lower risk of misuse.<sup id="cite_ref-34" class="reference"><a href="#cite_note-34"><span class="cite-bracket">[</span>34<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading3"><h3 id="Access_in_the_United_States">Access in the United States</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Buprenorphine/naloxone&action=edit&section=14" title="Edit section: Access in the United States"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>Before the <a href="/wiki/Drug_Addiction_Treatment_Act" title="Drug Addiction Treatment Act">Drug Addiction Treatment Act of 2000</a> (DATA), physicians were not allowed to prescribe narcotics to treat opioid dependence. People with narcotic dependence had to go to registered clinics to receive treatment. With DATA, Suboxone was the first medication approved for office-based treatment for opioid dependence.<sup id="cite_ref-SAM2016_1-3" class="reference"><a href="#cite_note-SAM2016-1"><span class="cite-bracket">[</span>1<span class="cite-bracket">]</span></a></sup> Suboxone has thus become widely used as a replacement for methadone as it can be prescribed by doctors in their offices, while methadone can only be provided at specialized addiction centers, of which there are a limited number, often making access difficult. Integrating Medication-Assisted Treatment into outpatient primary care practices improves patient access to Suboxone.<sup id="cite_ref-35" class="reference"><a href="#cite_note-35"><span class="cite-bracket">[</span>35<span class="cite-bracket">]</span></a></sup> Some physicians are also leading a movement to begin prescribing it out of the <a href="/wiki/Emergency_department" title="Emergency department">emergency department</a> (ED), as some small studies have shown ED-initiated Suboxone to be effective with people more likely to remain in addiction treatment compared to those either referred to addiction treatment programs or those receiving just a brief intervention in the department.<sup id="cite_ref-36" class="reference"><a href="#cite_note-36"><span class="cite-bracket">[</span>36<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-37" class="reference"><a href="#cite_note-37"><span class="cite-bracket">[</span>37<span class="cite-bracket">]</span></a></sup> </p><p>Access to Suboxone can be limited due to varying <a href="/wiki/Prior_authorization" title="Prior authorization">prior authorization</a> requirements across different <a href="/wiki/Insurer" class="mw-redirect" title="Insurer">insurers</a>. Prior authorization is used by insurance companies to limit certain medications' use by requiring approval before the insurance company will pay for them.<sup id="cite_ref-38" class="reference"><a href="#cite_note-38"><span class="cite-bracket">[</span>38<span class="cite-bracket">]</span></a></sup> This can influence a person's financial access and adherence. Financial access is determined through prior authorization approval, which the prescriber must request before the person can start the medication. The time it takes to have the request approved can delay the person starting the medication. The prior authorization process can also affect adherence because approval is needed for every prescription. This presents the potential for a gap in treatment and withdrawal symptoms as the person waits for approval. Several insurance companies, as well as <a href="/wiki/Medicaid" title="Medicaid">Medicaid</a> in various states, have removed the use of prior authorization for Suboxone in an attempt to increase access to this treatment.<sup id="cite_ref-39" class="reference"><a href="#cite_note-39"><span class="cite-bracket">[</span>39<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading3"><h3 id="Controversies">Controversies</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Buprenorphine/naloxone&action=edit&section=15" title="Edit section: Controversies"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>In July 2019, the British company <a href="/wiki/Reckitt_Benckiser_Group" class="mw-redirect" title="Reckitt Benckiser Group">Reckitt Benckiser Group</a> (RB Group) and its current/former affiliated entities (notably <a href="/wiki/Indivior" title="Indivior">Indivior</a>, which split from RB Group in 2014) settled with the <a href="/wiki/US_Department_of_Justice" class="mw-redirect" title="US Department of Justice">US Department of Justice</a> (DOJ) regarding the sale and marketing of brand name Suboxone (buprenorphine/naloxone).<sup id="cite_ref-CNN_Howard_40-0" class="reference"><a href="#cite_note-CNN_Howard-40"><span class="cite-bracket">[</span>40<span class="cite-bracket">]</span></a></sup> The non-prosecution agreement involves RB Group paying up to $1.4 billion, the largest settlement payment in U.S. history involving an opioid-class medication.<sup id="cite_ref-CNN_Howard_40-1" class="reference"><a href="#cite_note-CNN_Howard-40"><span class="cite-bracket">[</span>40<span class="cite-bracket">]</span></a></sup> This record was surpassed in October 2020, when Purdue Pharma reached an $8 billion settlement for claims related to injuries and deaths caused by the opioid epidemic, which includes criminal fines, forfeiture, and civil damages.<sup id="cite_ref-41" class="reference"><a href="#cite_note-41"><span class="cite-bracket">[</span>41<span class="cite-bracket">]</span></a></sup> The 2019 case alleged <a href="/wiki/Anti-competitive" class="mw-redirect" title="Anti-competitive">anti-competitive</a> behavior by RB Group and Indivior surrounding the expiration of their regulatory exclusivity for Suboxone sublingual tablets.<sup id="cite_ref-FTC_Release_42-0" class="reference"><a href="#cite_note-FTC_Release-42"><span class="cite-bracket">[</span>42<span class="cite-bracket">]</span></a></sup> The DOJ alleged that RB Group and Indivior employed a <a href="/wiki/Product_hopping" class="mw-redirect" title="Product hopping">product hopping</a> scheme (when a firm ceases production of a product upon expiration of regulatory exclusivity in favor of another product that still has regulatory exclusivity in order to prevent generic manufacturer competition) by misrepresenting that the Suboxone sublingual film formulation was safer than the sublingual tablet formulation because "children are less likely to be accidentally exposed to the film product".<sup id="cite_ref-FTC_Release_42-1" class="reference"><a href="#cite_note-FTC_Release-42"><span class="cite-bracket">[</span>42<span class="cite-bracket">]</span></a></sup> There was no scientific evidence for that claim.<sup id="cite_ref-DOJ_Indivior_18-1" class="reference"><a href="#cite_note-DOJ_Indivior-18"><span class="cite-bracket">[</span>18<span class="cite-bracket">]</span></a></sup> The company also sponsored a complaint to the FDA, expressing concern that buprenorphine/naloxone sublingual tablets (the very product they formerly produced) were unsafe, requesting that applications for regulatory approval of generic products by other pharmaceutical companies (their competitors) be rejected by the US <a href="/wiki/Food_and_Drug_Administration" title="Food and Drug Administration">Food and Drug Administration</a>.<sup id="cite_ref-FTC_Release_42-2" class="reference"><a href="#cite_note-FTC_Release-42"><span class="cite-bracket">[</span>42<span class="cite-bracket">]</span></a></sup> </p> <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=Buprenorphine/naloxone&action=edit&section=16" 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"> <div class="mw-references-wrap mw-references-columns"><ol class="references"> <li id="cite_note-SAM2016-1"><span class="mw-cite-backlink">^ <a href="#cite_ref-SAM2016_1-0"><sup><i><b>a</b></i></sup></a> <a href="#cite_ref-SAM2016_1-1"><sup><i><b>b</b></i></sup></a> <a href="#cite_ref-SAM2016_1-2"><sup><i><b>c</b></i></sup></a> <a href="#cite_ref-SAM2016_1-3"><sup><i><b>d</b></i></sup></a></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="https://www.samhsa.gov/medication-assisted-treatment/treatment/buprenorphine">"Buprenorphine"</a>. <i>www.samhsa.gov</i>. 31 May 2016<span class="reference-accessdate">. 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title="Opioid antagonist">Opioid antagonists</a></i> <ul><li><a href="/wiki/Naltrexone" title="Naltrexone">Naltrexone</a></li> <li><a href="/wiki/Nalmefene" title="Nalmefene">Nalmefene</a></li></ul></li> <li><a href="/wiki/Topiramate" title="Topiramate">Topiramate</a></li> <li><i><a href="/wiki/Adrenergic_agonist" title="Adrenergic agonist"><abbr title="Adrenergic agonist">AA</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 Adrenergic agonist</span></i> (<a href="/wiki/Clonidine" title="Clonidine">Clonidine</a>)</li> <li><a href="/wiki/Baclofen" title="Baclofen">Baclofen</a></li> <li><a href="/wiki/Phenibut" title="Phenibut">Phenibut</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Opioid_dependence" class="mw-redirect" title="Opioid dependence">Opioid dependence</a></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><i><a href="/wiki/Adrenergic_agonist" title="Adrenergic agonist"><abbr title="Adrenergic agonist">AA</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 Adrenergic agonist</span></i> (<a href="/wiki/Clonidine" title="Clonidine">Clonidine</a></li> <li><a href="/wiki/Lofexidine" title="Lofexidine">Lofexidine</a>)</li> <li><a href="/wiki/Ibogaine" title="Ibogaine">Ibogaine</a></li> <li><i><a href="/wiki/Opioid" title="Opioid">Opioids</a></i> <ul><li><a href="/wiki/Buprenorphine" title="Buprenorphine">Buprenorphine</a> (<a class="mw-selflink selflink">+naloxone</a>)</li> <li><a href="/wiki/Levacetylmethadol" title="Levacetylmethadol">Levacetylmethadol</a></li> <li><a href="/wiki/Methadone" title="Methadone">Methadone</a></li> <li><a href="/wiki/Dihydrocodeine" title="Dihydrocodeine">Dihydrocodeine</a></li> <li><a href="/wiki/Dihydroetorphine" title="Dihydroetorphine">Dihydroetorphine</a></li> <li><a href="/wiki/Hydromorphone" title="Hydromorphone">Hydromorphone (extended-release)</a></li> <li><a href="/wiki/Morphine" title="Morphine">Morphine (extended-release)</a></li></ul></li> <li><i><a href="/wiki/Opioid_antagonist" title="Opioid antagonist">Opioid antagonists</a></i> (<a href="/wiki/Naltrexone" title="Naltrexone">Naltrexone</a></li> <li><a href="/wiki/Nalmefene" title="Nalmefene">Nalmefene</a>)</li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Benzodiazepine_dependence" title="Benzodiazepine dependence">Benzodiazepine dependence</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><i><a href="/wiki/Adrenergic_agonist" title="Adrenergic agonist"><abbr title="Adrenergic agonist">AA</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 Adrenergic agonist</span></i> (<a href="/wiki/Clonidine" title="Clonidine">Clonidine</a>)</li> <li><i><a href="/wiki/Benzodiazepine" title="Benzodiazepine">Benzodiazepines</a></i> (<a href="/wiki/Diazepam" title="Diazepam">Diazepam</a></li> <li><a href="/wiki/Lorazepam" title="Lorazepam">Lorazepam</a></li> <li><a href="/wiki/Chlordiazepoxide" title="Chlordiazepoxide">Chlordiazepoxide</a></li> <li><a href="/wiki/Oxazepam" title="Oxazepam">Oxazepam</a>)</li> <li><i><a href="/wiki/Barbiturate" title="Barbiturate">Barbiturates</a></i> (<a href="/wiki/Phenobarbital" title="Phenobarbital">Phenobarbital</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="Opioid_receptor_modulators" style="padding:3px"><table class="nowraplinks 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:Opioid_receptor_modulators" title="Template:Opioid receptor modulators"><abbr title="View this template">v</abbr></a></li><li class="nv-talk"><a href="/wiki/Template_talk:Opioid_receptor_modulators" title="Template talk:Opioid receptor modulators"><abbr title="Discuss this template">t</abbr></a></li><li class="nv-edit"><a href="/wiki/Special:EditPage/Template:Opioid_receptor_modulators" title="Special:EditPage/Template:Opioid receptor modulators"><abbr title="Edit this template">e</abbr></a></li></ul></div><div id="Opioid_receptor_modulators" style="font-size:114%;margin:0 4em"><a href="/wiki/Opioid_receptor" title="Opioid receptor">Opioid 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/%CE%9C-opioid_receptor" title="Μ-opioid receptor">μ-opioid</a><br />(MOR)</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 id="Agonists(abridged;_full_list)" scope="row" class="navbox-group" style="width:1%">Agonists<br />(abridged;<br /> <a href="/wiki/List_of_opioids" title="List of opioids">full list</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/3-HO-PCP" title="3-HO-PCP">3-HO-PCP</a></li> <li><a href="/w/index.php?title=7-Acetoxymitragynine&action=edit&redlink=1" class="new" title="7-Acetoxymitragynine (page does not exist)">7-Acetoxymitragynine</a></li> <li><a href="/wiki/7-Hydroxymitragynine" title="7-Hydroxymitragynine">7-Hydroxymitragynine</a></li> <li><a href="/w/index.php?title=%CE%A8-Akuammigine&action=edit&redlink=1" class="new" title="Ψ-Akuammigine (page does not exist)">ψ-Akuammigine</a></li> <li><a href="/wiki/Chlornaltrexamine" class="mw-redirect" title="Chlornaltrexamine">α-Chlornaltrexamine</a></li> <li><a href="/w/index.php?title=Alpha-Narcotine&action=edit&redlink=1" class="new" title="Alpha-Narcotine (page does not exist)">α-Narcotine</a></li> <li><a href="/wiki/Acetyldihydrocodeine" title="Acetyldihydrocodeine">Acetyldihydrocodeine</a></li> <li><a href="/wiki/Acetylfentanyl" title="Acetylfentanyl">Acetylfentanyl</a></li> <li><a href="/wiki/Acrylfentanyl" title="Acrylfentanyl">Acrylfentanyl</a></li> <li><a href="/wiki/Adrenorphin" title="Adrenorphin">Adrenorphin (metorphamide)</a></li> <li><a href="/wiki/AH-7921" title="AH-7921">AH-7921</a></li> <li><a href="/wiki/Akuammicine" title="Akuammicine">Akuammicine</a></li> <li><a href="/w/index.php?title=Akuammidine&action=edit&redlink=1" class="new" title="Akuammidine (page does not exist)">Akuammidine</a></li> <li><a href="/wiki/Alfentanil" title="Alfentanil">Alfentanil</a></li> <li><a href="/wiki/Anileridine" title="Anileridine">Anileridine</a></li> <li><a href="/wiki/Apparicine" title="Apparicine">Apparicine</a></li> <li><a href="/wiki/Beta-Endorphin" class="mw-redirect" title="Beta-Endorphin">β-Endorphin</a></li> <li><a href="/w/index.php?title=Bovine_adrenal_medullary_peptide-12P&action=edit&redlink=1" class="new" title="Bovine adrenal medullary peptide-12P (page does not exist)">BAM-12P</a></li> <li><a href="/w/index.php?title=Bovine_adrenal_medullary_peptide-18P&action=edit&redlink=1" class="new" title="Bovine adrenal medullary peptide-18P (page does not exist)">BAM-18P</a></li> <li><a href="/w/index.php?title=Bovine_adrenal_medullary_peptide-22P&action=edit&redlink=1" class="new" title="Bovine adrenal medullary peptide-22P (page does not exist)">BAM-22P</a></li> <li><a href="/wiki/Benzhydrocodone" title="Benzhydrocodone">Benzhydrocodone</a></li> <li><a href="/wiki/Benzylmorphine" title="Benzylmorphine">Benzylmorphine</a></li> <li><a href="/wiki/Bezitramide" title="Bezitramide">Bezitramide</a></li> <li><a href="/wiki/Biphalin" title="Biphalin">Biphalin</a></li> <li><a href="/w/index.php?title=BU08070&action=edit&redlink=1" class="new" title="BU08070 (page does not exist)">BU08070</a></li> <li><a href="/wiki/Buprenorphine" title="Buprenorphine">Buprenorphine</a></li> <li><a href="/wiki/Butorphan" class="mw-redirect" title="Butorphan">Butorphan</a></li> <li><a href="/wiki/Butorphanol" title="Butorphanol">Butorphanol</a></li> <li><a href="/wiki/Butyrfentanyl" title="Butyrfentanyl">Butyrfentanyl</a></li> <li><a href="/wiki/BW373U86" title="BW373U86">BW373U86</a></li> <li><a href="/wiki/Carfentanil" title="Carfentanil">Carfentanil</a></li> <li><a href="/wiki/Casokefamide" title="Casokefamide">Casokefamide</a></li> <li><a href="/wiki/Cebranopadol" title="Cebranopadol">Cebranopadol</a></li> <li><a href="/wiki/Chloroxymorphamine" title="Chloroxymorphamine">Chloroxymorphamine</a></li> <li><a href="/wiki/Codeine" title="Codeine">Codeine</a></li> <li><a href="/wiki/DADLE" title="DADLE">DADLE</a></li> <li><a href="/wiki/DAMGO" title="DAMGO">DAMGO (DAGO)</a></li> <li><a href="/wiki/Dermorphin" title="Dermorphin">Dermorphin</a></li> <li><a href="/wiki/Desmetramadol" title="Desmetramadol">Desmetramadol (desmethyltramadol)</a></li> <li><a href="/wiki/Desomorphine" title="Desomorphine">Desomorphine</a></li> <li><a href="/wiki/Dextromoramide" title="Dextromoramide">Dextromoramide</a></li> <li><a href="/wiki/Dextropropoxyphene" title="Dextropropoxyphene">Dextropropoxyphene (propoxyphene)</a></li> <li><a href="/wiki/Dezocine" title="Dezocine">Dezocine</a></li> <li><a href="/wiki/Dimenoxadol" title="Dimenoxadol">Dimenoxadol</a></li> <li><a href="/wiki/Dimethylaminopivalophenone" title="Dimethylaminopivalophenone">Dimethylaminopivalophenone</a></li> <li><a href="/wiki/Eluxadoline" title="Eluxadoline">Eluxadoline</a></li> <li><a href="/wiki/Heroin" title="Heroin">Diamorphine (heroin)</a></li> <li><a href="/wiki/Dihydrocodeine" title="Dihydrocodeine">Dihydrocodeine</a></li> <li><a href="/wiki/Dihydroetorphine" title="Dihydroetorphine">Dihydroetorphine</a></li> <li><a href="/wiki/Dihydromorphine" title="Dihydromorphine">Dihydromorphine</a></li> <li><a href="/wiki/Dinalbuphine_sebacate" title="Dinalbuphine sebacate">Dinalbuphine sebacate</a></li> <li><a href="/wiki/Diphenoxylate" title="Diphenoxylate">Diphenoxylate</a></li> <li><a href="/wiki/Dipipanone" title="Dipipanone">Dipipanone</a></li> <li><a href="/wiki/Dynorphin_A" title="Dynorphin A">Dynorphin A</a></li> <li><a href="/wiki/Embutramide" title="Embutramide">Embutramide</a></li> <li><a href="/wiki/Endomorphin-1" title="Endomorphin-1">Endomorphin-1</a></li> <li><a href="/wiki/Endomorphin-2" title="Endomorphin-2">Endomorphin-2</a></li> <li><a href="/wiki/Eseroline" title="Eseroline">Eseroline</a></li> <li><a href="/wiki/Ethylmorphine" title="Ethylmorphine">Ethylmorphine</a></li> <li><a href="/wiki/Etorphine" title="Etorphine">Etorphine</a></li> <li><a href="/wiki/Fentanyl" title="Fentanyl">Fentanyl</a></li> <li><a href="/wiki/Fluorophen" title="Fluorophen">Fluorophen</a></li> <li><a href="/wiki/Frakefamide" title="Frakefamide">Frakefamide</a></li> <li><a href="/wiki/Furanylfentanyl" title="Furanylfentanyl">Furanylfentanyl</a></li> <li><a href="/wiki/Hemorphin-4" title="Hemorphin-4">Hemorphin-4</a></li> <li><a href="/wiki/Herkinorin" title="Herkinorin">Herkinorin</a></li> <li><a href="/wiki/Hodgkinsine" title="Hodgkinsine">Hodgkinsine</a></li> <li><a href="/wiki/Hydrocodone" title="Hydrocodone">Hydrocodone</a></li> <li><a href="/wiki/Hydromorphinol" title="Hydromorphinol">Hydromorphinol</a></li> <li><a href="/wiki/Hydromorphone" title="Hydromorphone">Hydromorphone</a></li> <li><a href="/wiki/IBNtxA" title="IBNtxA">IBNtxA</a></li> <li><a href="/wiki/Ketamine" title="Ketamine">Ketamine</a></li> <li><a href="/wiki/Ketobemidone" title="Ketobemidone">Ketobemidone</a></li> <li><a href="/wiki/Mitragyna_speciosa" title="Mitragyna speciosa">Kratom</a></li> <li><a href="/wiki/Laudanosine" title="Laudanosine">Laudanosine</a></li> <li><a href="/wiki/Lefetamine" title="Lefetamine">Lefetamine</a></li> <li><a href="/wiki/Leu-enkephalin" title="Leu-enkephalin">Leu-enkephalin</a></li> <li><a href="/wiki/Levacetylmethadol" title="Levacetylmethadol">Levacetylmethadol</a></li> <li><a href="/wiki/Levomethorphan" title="Levomethorphan">Levomethorphan</a></li> <li><a href="/wiki/Levorphanol" title="Levorphanol">Levorphanol</a></li> <li><a href="/w/index.php?title=Lexanopadol&action=edit&redlink=1" class="new" title="Lexanopadol (page does not exist)">Lexanopadol</a></li> <li><a href="/wiki/Loperamide" title="Loperamide">Loperamide</a></li> <li><a href="/wiki/Loxicodegol" class="mw-redirect" title="Loxicodegol">Loxicodegol</a></li> <li><a href="/wiki/LS-115509" title="LS-115509">LS-115509</a></li> <li><a href="/wiki/Matrine" title="Matrine">Matrine</a></li> <li><a href="/wiki/Meptazinol" title="Meptazinol">Meptazinol</a></li> <li><a href="/wiki/Met-enkephalin" title="Met-enkephalin">Met-enkephalin (metenkefalin)</a></li> <li><a href="/wiki/Methadone" title="Methadone">Methadone</a></li> <li><a href="/wiki/Metkefamide" title="Metkefamide">Metkefamide</a></li> <li><a href="/wiki/Metopon" title="Metopon">Metopon</a></li> <li><a href="/wiki/Mitragynine" title="Mitragynine">Mitragynine</a></li> <li><a href="/wiki/Mitragynine_pseudoindoxyl" title="Mitragynine pseudoindoxyl">Mitragynine pseudoindoxyl</a></li> <li><a href="/wiki/Morphiceptin" title="Morphiceptin">Morphiceptin</a></li> <li><a href="/wiki/Morphine" title="Morphine">Morphine</a></li> <li><a href="/wiki/Nalbuphine" title="Nalbuphine">Nalbuphine</a></li> <li><a href="/w/index.php?title=Naloxone_benzoylhydrazone&action=edit&redlink=1" class="new" title="Naloxone benzoylhydrazone (page does not exist)">NalBzOH</a></li> <li><a href="/wiki/Nalmexone" title="Nalmexone">Nalmexone</a></li> <li><a href="/wiki/Naltalimide" title="Naltalimide">Naltalimide</a></li> <li><a href="/w/index.php?title=Neopine&action=edit&redlink=1" class="new" title="Neopine (page does not exist)">Neopine</a></li> <li><a href="/wiki/NFEPP" title="NFEPP">NFEPP</a></li> <li><a href="/wiki/Nicocodeine" title="Nicocodeine">Nicocodeine</a></li> <li><a href="/wiki/Nicodicodine" title="Nicodicodine">Nicodicodine</a></li> <li><a href="/wiki/Nicomorphine" title="Nicomorphine">Nicomorphine</a></li> <li><a href="/wiki/Norketamine" title="Norketamine">Norketamine</a></li> <li><a href="/wiki/Nufenoxole" title="Nufenoxole">Nufenoxole</a></li> <li><a href="/wiki/Octreotide" title="Octreotide">Octreotide</a></li> <li><a href="/wiki/Oliceridine" title="Oliceridine">Oliceridine</a></li> <li><a href="/wiki/Oxycodegol" title="Oxycodegol">Oxycodegol</a></li> <li><a href="/wiki/Oxymorphone-3-methoxynaltrexonazine" title="Oxymorphone-3-methoxynaltrexonazine">OM-3-MNZ</a></li> <li><a href="/wiki/Oripavine" title="Oripavine">Oripavine</a></li> <li><a href="/wiki/Oxycodone" title="Oxycodone">Oxycodone</a></li> <li><a href="/wiki/Oxymorphazone" title="Oxymorphazone">Oxymorphazone</a></li> <li><a href="/w/index.php?title=Oxymorphonazine&action=edit&redlink=1" class="new" title="Oxymorphonazine (page does not exist)">Oxymorphonazine</a></li> <li><a href="/wiki/Oxymorphone" title="Oxymorphone">Oxymorphone</a></li> <li><a href="/w/index.php?title=Oxymorphone_phenylhydrazone&action=edit&redlink=1" class="new" title="Oxymorphone phenylhydrazone (page does not exist)">Oxymorphone phenylhydrazone</a></li> <li><a href="/w/index.php?title=Oxymorphone_p-nitrophenylhydrazone&action=edit&redlink=1" class="new" title="Oxymorphone p-nitrophenylhydrazone (page does not exist)">OxyPNPH</a></li> <li><i><a href="/wiki/Papaver_somniferum" title="Papaver somniferum">Papaver somniferum</a></i> (<a href="/wiki/Opium" title="Opium">opium</a>)</li> <li><a href="/wiki/Pentazocine" title="Pentazocine">Pentazocine</a></li> <li><a href="/wiki/Pericine" title="Pericine">Pericine</a></li> <li><a href="/wiki/Pethidine" title="Pethidine">Pethidine (meperidine)</a></li> <li><a href="/wiki/Phenazocine" title="Phenazocine">Phenazocine</a></li> <li><a href="/wiki/Phencyclidine" title="Phencyclidine">Phencyclidine</a></li> <li><a href="/wiki/Piminodine" title="Piminodine">Piminodine</a></li> <li><a href="/wiki/Piritramide" title="Piritramide">Piritramide</a></li> <li><a href="/w/index.php?title=PL-017&action=edit&redlink=1" class="new" title="PL-017 (page does not exist)">PL-017</a></li> <li><a href="/wiki/Prodine" title="Prodine">Prodine</a></li> <li><a href="/wiki/Propiram" title="Propiram">Propiram</a></li> <li><a href="/wiki/PZM21" title="PZM21">PZM21</a></li> <li><a href="/wiki/Methorphan" title="Methorphan">Racemethorphan</a></li> <li><a href="/wiki/Racemorphan" title="Racemorphan">Racemorphan</a></li> <li><a href="/wiki/Remifentanil" title="Remifentanil">Remifentanil</a></li> <li><a href="/wiki/Salsolinol" title="Salsolinol">Salsolinol</a></li> <li><a href="/wiki/SC-17599" title="SC-17599">SC-17599</a></li> <li><a href="/wiki/Sinomenine" title="Sinomenine">Sinomenine</a></li> <li><a href="/wiki/Sufentanil" title="Sufentanil">Sufentanil</a></li> <li><a href="/wiki/Tapentadol" title="Tapentadol">Tapentadol</a></li> <li><a href="/wiki/Tetrahydropapaveroline" title="Tetrahydropapaveroline">Tetrahydropapaveroline</a></li> <li><a href="/wiki/TH-030418" title="TH-030418">TH-030418</a></li> <li><a href="/wiki/Thebaine" title="Thebaine">Thebaine</a></li> <li><a href="/wiki/Thienorphine" title="Thienorphine">Thienorphine</a></li> <li><a href="/wiki/Tianeptine" title="Tianeptine">Tianeptine</a></li> <li><a href="/wiki/Tilidine" title="Tilidine">Tilidine</a></li> <li><a href="/wiki/Tramadol" title="Tramadol">Tramadol</a></li> <li><a href="/wiki/Trimebutine" title="Trimebutine">Trimebutine</a></li> <li><a href="/wiki/TRIMU_5" title="TRIMU 5">TRIMU 5</a></li> <li><a href="/wiki/TRV734" title="TRV734">TRV734</a></li> <li><a href="/w/index.php?title=Tubotaiwine&action=edit&redlink=1" class="new" title="Tubotaiwine (page does not exist)">Tubotaiwine</a></li> <li><a href="/wiki/U-47700" title="U-47700">U-47700</a></li> <li><a href="/wiki/Valorphin" title="Valorphin">Valorphin</a></li> <li><a href="/wiki/Viminol" title="Viminol">Viminol</a></li> <li><a href="/wiki/Xorphanol" title="Xorphanol">Xorphanol</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%">Antagonists</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/Picenadol" title="Picenadol">(3S,4S)-Picenadol</a></li> <li><a href="/wiki/Viminol" title="Viminol">2-(S)-N,N-(R)-Viminol</a></li> <li><a href="/w/index.php?title=3CS-nalmefene&action=edit&redlink=1" class="new" title="3CS-nalmefene (page does not exist)">3CS-nalmefene</a></li> <li><a href="/wiki/4-Caffeoyl-1,5-quinide" title="4-Caffeoyl-1,5-quinide">4-Caffeoyl-1,5-quinide</a></li> <li><a href="/wiki/4%E2%80%B2-Hydroxyflavanone" class="mw-redirect" title="4′-Hydroxyflavanone">4′-Hydroxyflavanone</a></li> <li><a href="/wiki/4%27,7-Dihydroxyflavone" title="4',7-Dihydroxyflavone">4',7-Dihydroxyflavone</a></li> <li><a href="/wiki/6%CE%B2-Naltrexol" title="6β-Naltrexol">6β-Naltrexol</a></li> <li><a href="/wiki/6%CE%B2-Naltrexol-d4" title="6β-Naltrexol-d4">6β-Naltrexol-d4</a></li> <li><a href="/wiki/18-Methoxycoronaridine" title="18-Methoxycoronaridine">18-MC</a></li> <li><a href="/wiki/Alpha-Gliadin" class="mw-redirect" title="Alpha-Gliadin">α-Gliadin</a></li> <li><a href="/wiki/Chlornaltrexamine" class="mw-redirect" title="Chlornaltrexamine">β-Chlornaltrexamine</a></li> <li><a href="/wiki/Beta-Funaltrexamine" class="mw-redirect" title="Beta-Funaltrexamine">β-Funaltrexamine</a></li> <li><a href="/wiki/Akuammine" title="Akuammine">Akuammine</a></li> <li><a href="/wiki/Alvimopan" title="Alvimopan">Alvimopan</a></li> <li><a href="/wiki/AM-251_(drug)" title="AM-251 (drug)">AM-251</a></li> <li><a href="/wiki/Apigenin" title="Apigenin">Apigenin</a></li> <li><a href="/wiki/AT-076" title="AT-076">AT-076</a></li> <li><a href="/wiki/Axelopran" title="Axelopran">Axelopran</a></li> <li><a href="/wiki/Bevenopran" title="Bevenopran">Bevenopran</a></li> <li><a href="/wiki/Catechin" title="Catechin">Catechin</a></li> <li><a href="/wiki/Epicatechin_gallate" title="Epicatechin gallate">Catechin gallate</a></li> <li><a href="/wiki/Clocinnamox" title="Clocinnamox">Clocinnamox</a></li> <li>CTAP</li> <li><a href="/w/index.php?title=CTOP&action=edit&redlink=1" class="new" title="CTOP (page does not exist)">CTOP</a></li> <li><a href="/w/index.php?title=Cyclofoxy&action=edit&redlink=1" class="new" title="Cyclofoxy (page does not exist)">Cyclofoxy</a></li> <li><a href="/wiki/Cyprodime" title="Cyprodime">Cyprodime</a></li> <li><a href="/wiki/Diacetylnalorphine" title="Diacetylnalorphine">Diacetylnalorphine</a></li> <li><a href="/wiki/Diprenorphine" title="Diprenorphine">Diprenorphine</a></li> <li><a href="/wiki/Epicatechin_gallate" title="Epicatechin gallate">ECG</a></li> <li><a href="/wiki/Gallocatechol" title="Gallocatechol">EGC</a></li> <li><a href="/wiki/Epicatechin" class="mw-redirect" title="Epicatechin">Epicatechin</a></li> <li><a href="/wiki/Eptazocine" title="Eptazocine">Eptazocine</a></li> <li><a href="/wiki/Gemazocine" title="Gemazocine">Gemazocine</a></li> <li><a href="/w/index.php?title=Ginsenoside_R&action=edit&redlink=1" class="new" title="Ginsenoside R (page does not exist)">Ginsenoside R</a></li> <li><a href="/wiki/Hyperoside" title="Hyperoside">Hyperoside</a></li> <li><a href="/wiki/Ibogaine" title="Ibogaine">Ibogaine</a></li> <li><a href="/wiki/JDTic" title="JDTic">JDTic</a></li> <li><a href="/wiki/Levallorphan" title="Levallorphan">Levallorphan</a></li> <li><a href="/wiki/Lobeline" title="Lobeline">Lobeline</a></li> <li><a href="/wiki/LY-255582" title="LY-255582">LY-255582</a></li> <li><a href="/wiki/LY-2196044" class="mw-redirect" title="LY-2196044">LY-2196044</a></li> <li><a href="/wiki/Methocinnamox" title="Methocinnamox">Methocinnamox</a></li> <li><a href="/wiki/Methylnaltrexone" title="Methylnaltrexone">Methylnaltrexone</a></li> <li><a href="/w/index.php?title=Methylsamidorphan_chloride&action=edit&redlink=1" class="new" title="Methylsamidorphan chloride (page does not exist)">Methylsamidorphan chloride</a></li> <li><a href="/wiki/Naldemedine" title="Naldemedine">Naldemedine</a></li> <li><a href="/wiki/Nalmefene" title="Nalmefene">Nalmefene</a></li> <li><a href="/wiki/Nalodeine" title="Nalodeine">Nalodeine (N-allylnorcodeine)</a></li> <li><a href="/wiki/Nalorphine" title="Nalorphine">Nalorphine</a></li> <li><a href="/wiki/Nalorphine_dinicotinate" title="Nalorphine dinicotinate">Nalorphine dinicotinate</a></li> <li><a href="/wiki/Naloxazone" title="Naloxazone">Naloxazone</a></li> <li><a href="/wiki/Naloxegol" title="Naloxegol">Naloxegol</a></li> <li><a href="/wiki/Naloxol" title="Naloxol">Naloxol</a></li> <li><a href="/wiki/Naloxonazine" title="Naloxonazine">Naloxonazine</a></li> <li><a href="/wiki/Naloxone" title="Naloxone">Naloxone</a></li> <li><a href="/w/index.php?title=Naltrexazone&action=edit&redlink=1" class="new" title="Naltrexazone (page does not exist)">Naltrexazone</a></li> <li><a href="/w/index.php?title=Naltrexonazine&action=edit&redlink=1" class="new" title="Naltrexonazine (page does not exist)">Naltrexonazine</a></li> <li><a href="/wiki/Naltrexone" title="Naltrexone">Naltrexone</a></li> <li><a href="/wiki/Naltrindole" title="Naltrindole">Naltrindole</a></li> <li><a href="/wiki/Naringenin" title="Naringenin">Naringenin</a></li> <li><a href="/wiki/Noribogaine" title="Noribogaine">Noribogaine</a></li> <li><a href="/wiki/Oxilorphan" title="Oxilorphan">Oxilorphan</a></li> <li><a href="/wiki/Pawhuskin_A" title="Pawhuskin A">Pawhuskin A</a></li> <li><a href="/wiki/Rimonabant" title="Rimonabant">Rimonabant</a></li> <li><a href="/wiki/Quadazocine" title="Quadazocine">Quadazocine</a></li> <li><a href="/wiki/Samidorphan" title="Samidorphan">Samidorphan</a></li> <li><a href="/wiki/Taxifolin" title="Taxifolin">Taxifolin</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/%CE%94-opioid_receptor" title="Δ-opioid receptor">δ-opioid</a><br />(DOR)</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%">Agonists</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="/w/index.php?title=3CS-nalmefene&action=edit&redlink=1" class="new" title="3CS-nalmefene (page does not exist)">3CS-nalmefene</a></li> <li><a href="/wiki/6%27-Guanidinonaltrindole" title="6'-Guanidinonaltrindole">6'-GNTI</a></li> <li><a href="/wiki/7-Spiroindanyloxymorphone" title="7-Spiroindanyloxymorphone">7-SIOM</a></li> <li><a href="/wiki/ADL-5747" title="ADL-5747">ADL-5747 (PF-04856881)</a></li> <li><a href="/wiki/ADL-5859" title="ADL-5859">ADL-5859</a></li> <li><a href="/wiki/Alazocine" title="Alazocine">Alazocine (SKF-10047)</a></li> <li><a href="/wiki/Amoxapine" title="Amoxapine">Amoxapine</a></li> <li><a href="/wiki/ARM390" title="ARM390">AR-M100390 (ARM390)</a></li> <li><a href="/wiki/AZD2327" class="mw-redirect" title="AZD2327">AZD2327</a></li> <li><a href="/wiki/Beta-Endorphin" class="mw-redirect" title="Beta-Endorphin">β-Endorphin</a></li> <li><a href="/w/index.php?title=Bovine_adrenal_medullary_peptide-18P&action=edit&redlink=1" class="new" title="Bovine adrenal medullary peptide-18P (page does not exist)">BAM-18P</a></li> <li><a href="/wiki/Biphalin" title="Biphalin">Biphalin</a></li> <li><a href="/wiki/BU-48" title="BU-48">BU-48</a></li> <li><a href="/wiki/Butorphan" class="mw-redirect" title="Butorphan">Butorphan</a></li> <li><a href="/wiki/Butorphanol" title="Butorphanol">Butorphanol</a></li> <li><a href="/wiki/BW373U86" title="BW373U86">BW373U86</a></li> <li><a href="/wiki/Casokefamide" title="Casokefamide">Casokefamide</a></li> <li><a href="/wiki/Cebranopadol" title="Cebranopadol">Cebranopadol</a></li> <li><a href="/wiki/Codeine" title="Codeine">Codeine</a></li> <li><a href="/wiki/Cyclazocine" title="Cyclazocine">Cyclazocine</a></li> <li><a href="/wiki/DADLE" title="DADLE">DADLE</a></li> <li><a href="/wiki/Deltorphin" title="Deltorphin">Deltorphin A</a></li> <li><a href="/wiki/Deltorphin_I" title="Deltorphin I">Deltorphin I</a></li> <li><a href="/w/index.php?title=Deltorphin_II&action=edit&redlink=1" class="new" title="Deltorphin II (page does not exist)">Deltorphin II</a></li> <li><a href="/wiki/Desmethylclozapine" title="Desmethylclozapine">Desmethylclozapine</a></li> <li><a href="/wiki/Desmetramadol" title="Desmetramadol">Desmetramadol (desmethyltramadol)</a></li> <li><a href="/wiki/Dezocine" title="Dezocine">Dezocine</a></li> <li><a href="/wiki/Heroin" title="Heroin">Diamorphine (heroin)</a></li> <li><a href="/wiki/Dihydroetorphine" title="Dihydroetorphine">Dihydroetorphine</a></li> <li><a href="/wiki/Dihydromorphine" title="Dihydromorphine">Dihydromorphine</a></li> <li><a href="/wiki/DPDPE" title="DPDPE">DPDPE</a></li> <li><a href="/wiki/DPI-221" title="DPI-221">DPI-221</a></li> <li><a href="/wiki/DPI-3290" title="DPI-3290">DPI-3290</a></li> <li><a href="/w/index.php?title=(D-Ser2,_Leu5,_Thr6)-Enkephalin&action=edit&redlink=1" class="new" title="(D-Ser2, Leu5, Thr6)-Enkephalin (page does not exist)">DSLET</a></li> <li><a href="/wiki/Ethylketazocine" title="Ethylketazocine">Ethylketazocine</a></li> <li><a href="/wiki/Etorphine" title="Etorphine">Etorphine</a></li> <li><a href="/wiki/Fentanyl" title="Fentanyl">Fentanyl</a></li> <li><a href="/w/index.php?title=Fentanyl_isothiocyanate&action=edit&redlink=1" class="new" title="Fentanyl isothiocyanate (page does not exist)">FIT</a></li> <li><a href="/wiki/Fluorophen" title="Fluorophen">Fluorophen</a></li> <li><a href="/wiki/Hemorphin-4" title="Hemorphin-4">Hemorphin-4</a></li> <li><a href="/wiki/Hydrocodone" title="Hydrocodone">Hydrocodone</a></li> <li><a href="/wiki/Hydromorphone" title="Hydromorphone">Hydromorphone</a></li> <li><a href="/wiki/Ibogaine" title="Ibogaine">Ibogaine</a></li> <li><a href="/wiki/Isomethadone" title="Isomethadone">Isomethadone</a></li> <li><a href="/wiki/JNJ-20788560" title="JNJ-20788560">JNJ-20788560</a></li> <li><a href="/wiki/KNT-127" title="KNT-127">KNT-127</a></li> <li><a href="/wiki/Mitragyna_speciosa" title="Mitragyna speciosa">Kratom</a></li> <li><a href="/wiki/Laudanosine" title="Laudanosine">Laudanosine</a></li> <li><a href="/wiki/Leu-enkephalin" title="Leu-enkephalin">Leu-enkephalin</a></li> <li><a href="/wiki/Levomethorphan" title="Levomethorphan">Levomethorphan</a></li> <li><a href="/wiki/Levorphanol" title="Levorphanol">Levorphanol</a></li> <li><a href="/w/index.php?title=Lexanopadol&action=edit&redlink=1" class="new" title="Lexanopadol (page does not exist)">Lexanopadol</a></li> <li><a href="/wiki/Lofentanil" title="Lofentanil">Lofentanil</a></li> <li><a href="/wiki/Met-enkephalin" title="Met-enkephalin">Met-enkephalin (metenkefalin)</a></li> <li><a href="/wiki/Metazocine" title="Metazocine">Metazocine</a></li> <li><a href="/wiki/Metkefamide" title="Metkefamide">Metkefamide</a></li> <li><a href="/wiki/Mitragynine" title="Mitragynine">Mitragynine</a></li> <li><a href="/wiki/Mitragynine_pseudoindoxyl" title="Mitragynine pseudoindoxyl">Mitragynine pseudoindoxyl</a></li> <li><a href="/wiki/Morphine" title="Morphine">Morphine</a></li> <li><a href="/wiki/N-Phenethyl-14-ethoxymetopon" title="N-Phenethyl-14-ethoxymetopon">N-Phenethyl-14-ethoxymetopon</a></li> <li><a href="/wiki/Norbuprenorphine" title="Norbuprenorphine">Norbuprenorphine</a></li> <li><a href="/w/index.php?title=Naloxone_benzoylhydrazone&action=edit&redlink=1" class="new" title="Naloxone benzoylhydrazone (page does not exist)">NalBzOH</a></li> <li><a href="/wiki/Oripavine" title="Oripavine">Oripavine</a></li> <li><a href="/wiki/Oxycodone" title="Oxycodone">Oxycodone</a></li> <li><a href="/wiki/Oxymorphone" title="Oxymorphone">Oxymorphone</a></li> <li><a href="/wiki/Pethidine" title="Pethidine">Pethidine (meperidine)</a></li> <li><a href="/wiki/Proglumide" title="Proglumide">Proglumide</a></li> <li><a href="/wiki/Methorphan" title="Methorphan">Racemethorphan</a></li> <li><a href="/wiki/Racemorphan" title="Racemorphan">Racemorphan</a></li> <li><a href="/wiki/RWJ-394674" title="RWJ-394674">RWJ-394674</a></li> <li><a href="/wiki/Samidorphan" title="Samidorphan">Samidorphan</a></li> <li><a href="/w/index.php?title=SB-235863&action=edit&redlink=1" class="new" title="SB-235863 (page does not exist)">SB-235863</a></li> <li><a href="/wiki/SNC-80" title="SNC-80">SNC-80</a></li> <li><a href="/w/index.php?title=SNC-162&action=edit&redlink=1" class="new" title="SNC-162 (page does not exist)">SNC-162</a></li> <li><a href="/wiki/TAN-67" title="TAN-67">TAN-67 (SB-205,607)</a></li> <li><a href="/wiki/TH-030418" title="TH-030418">TH-030418</a></li> <li><a href="/wiki/Thebaine" title="Thebaine">Thebaine</a></li> <li><a href="/wiki/C-8813" title="C-8813">Thiobromadol (C-8813)</a></li> <li><a href="/wiki/Tonazocine" title="Tonazocine">Tonazocine</a></li> <li><a href="/wiki/Tramadol" title="Tramadol">Tramadol</a></li> <li><a href="/w/index.php?title=TRV250&action=edit&redlink=1" class="new" title="TRV250 (page does not exist)">TRV250</a></li> <li><a href="/wiki/Xorphanol" title="Xorphanol">Xorphanol</a></li> <li><a href="/wiki/Zenazocine" title="Zenazocine">Zenazocine</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%">Antagonists</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/4%27,7-Dihydroxyflavone" title="4',7-Dihydroxyflavone">4',7-Dihydroxyflavone</a></li> <li><a href="/w/index.php?title=Naltrindole-5%27-isothiocyanate&action=edit&redlink=1" class="new" title="Naltrindole-5'-isothiocyanate (page does not exist)">5'-NTII</a></li> <li><a href="/wiki/6%CE%B2-Naltrexol" title="6β-Naltrexol">6β-Naltrexol</a></li> <li><a href="/wiki/6%CE%B2-Naltrexol-d4" title="6β-Naltrexol-d4">6β-Naltrexol-d4</a></li> <li><a href="/w/index.php?title=Alpha-Santolol&action=edit&redlink=1" class="new" title="Alpha-Santolol (page does not exist)">α-Santolol</a></li> <li><a href="/wiki/Chlornaltrexamine" class="mw-redirect" title="Chlornaltrexamine">β-Chlornaltrexamine</a></li> <li><a href="/wiki/Apigenin" title="Apigenin">Apigenin</a></li> <li><a href="/wiki/AT-076" title="AT-076">AT-076</a></li> <li><a href="/wiki/Axelopran" title="Axelopran">Axelopran</a></li> <li><a href="/wiki/Bevenopran" title="Bevenopran">Bevenopran</a></li> <li><a href="/w/index.php?title=7-Benzylidenenaltrexone&action=edit&redlink=1" class="new" title="7-Benzylidenenaltrexone (page does not exist)">BNTX</a></li> <li><a href="/wiki/Catechin" title="Catechin">Catechin</a></li> <li><a href="/wiki/Epicatechin_gallate" title="Epicatechin gallate">Catechin gallate</a></li> <li><a href="/wiki/Clocinnamox" title="Clocinnamox">Clocinnamox</a></li> <li><a href="/wiki/Diacetylnalorphine" title="Diacetylnalorphine">Diacetylnalorphine</a></li> <li><a href="/wiki/Diprenorphine" title="Diprenorphine">Diprenorphine</a></li> <li><a href="/wiki/Epicatechin_gallate" title="Epicatechin gallate">ECG</a></li> <li><a href="/wiki/Gallocatechol" title="Gallocatechol">EGC</a></li> <li><a href="/wiki/Eluxadoline" title="Eluxadoline">Eluxadoline</a></li> <li><a href="/wiki/Epicatechin" class="mw-redirect" title="Epicatechin">Epicatechin</a></li> <li><a href="/w/index.php?title=ICI-154129&action=edit&redlink=1" class="new" title="ICI-154129 (page does not exist)">ICI-154129</a></li> <li><a href="/w/index.php?title=ICI-174864&action=edit&redlink=1" class="new" title="ICI-174864 (page does not exist)">ICI-174864</a></li> <li><a href="/wiki/LY-255582" title="LY-255582">LY-255582</a></li> <li><a href="/wiki/LY-2196044" class="mw-redirect" title="LY-2196044">LY-2196044</a></li> <li><a href="/wiki/Methylnaltrexone" title="Methylnaltrexone">Methylnaltrexone</a></li> <li><a href="/w/index.php?title=Methylnaltrindole&action=edit&redlink=1" class="new" title="Methylnaltrindole (page does not exist)">Methylnaltrindole</a></li> <li><a href="/w/index.php?title=N-Benzylnaltrindole&action=edit&redlink=1" class="new" title="N-Benzylnaltrindole (page does not exist)">N-Benzylnaltrindole</a></li> <li><a href="/wiki/Nalmefene" title="Nalmefene">Nalmefene</a></li> <li><a href="/wiki/Nalorphine" title="Nalorphine">Nalorphine</a></li> <li><a href="/wiki/Naltrexone" title="Naltrexone">Naltrexone</a></li> <li><a href="/wiki/Naltriben" title="Naltriben">Naltriben</a></li> <li><a href="/wiki/Naltrindole" title="Naltrindole">Naltrindole</a></li> <li><a href="/wiki/Naloxone" title="Naloxone">Naloxone</a></li> <li><a href="/wiki/Naringenin" title="Naringenin">Naringenin</a></li> <li><a href="/wiki/Noribogaine" title="Noribogaine">Noribogaine</a></li> <li><a href="/wiki/Pawhuskin_A" title="Pawhuskin A">Pawhuskin A</a></li> <li><a href="/wiki/Quadazocine" title="Quadazocine">Quadazocine</a></li> <li><a href="/w/index.php?title=SDM25N&action=edit&redlink=1" class="new" title="SDM25N (page does not exist)">SDM25N</a></li> <li><a href="/wiki/SoRI-9409" title="SoRI-9409">SoRI-9409</a></li> <li><a href="/wiki/Taxifolin" title="Taxifolin">Taxifolin</a></li> <li><a href="/wiki/Thienorphine" title="Thienorphine">Thienorphine</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/%CE%9A-opioid_receptor" title="Κ-opioid receptor">κ-opioid</a><br />(KOR)</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%">Agonists</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="/w/index.php?title=3CS-nalmefene&action=edit&redlink=1" class="new" title="3CS-nalmefene (page does not exist)">3CS-nalmefene</a></li> <li><a href="/wiki/6%27-Guanidinonaltrindole" title="6'-Guanidinonaltrindole">6'-GNTI</a></li> <li><a href="/wiki/8-Carboxamidocyclazocine" title="8-Carboxamidocyclazocine">8-CAC</a></li> <li><a href="/wiki/18-Methoxycoronaridine" title="18-Methoxycoronaridine">18-MC</a></li> <li><a href="/wiki/14-Methoxymetopon" title="14-Methoxymetopon">14-Methoxymetopon</a></li> <li><a href="/wiki/Chlornaltrexamine" class="mw-redirect" title="Chlornaltrexamine">β-Chlornaltrexamine</a></li> <li><a href="/wiki/Beta-Funaltrexamine" class="mw-redirect" title="Beta-Funaltrexamine">β-Funaltrexamine</a></li> <li><a href="/wiki/Adrenorphin" title="Adrenorphin">Adrenorphin (metorphamide)</a></li> <li><a href="/wiki/Akuammicine" title="Akuammicine">Akuammicine</a></li> <li><a href="/wiki/Alazocine" title="Alazocine">Alazocine (SKF-10047)</a></li> <li><a href="/wiki/Allomatrine" class="mw-redirect" title="Allomatrine">Allomatrine</a></li> <li><a href="/w/index.php?title=Apadoline&action=edit&redlink=1" class="new" title="Apadoline (page does not exist)">Apadoline</a></li> <li><a href="/wiki/Asimadoline" title="Asimadoline">Asimadoline</a></li> <li><a href="/w/index.php?title=Bovine_adrenal_medullary_peptide-12P&action=edit&redlink=1" class="new" title="Bovine adrenal medullary peptide-12P (page does not exist)">BAM-12P</a></li> <li><a href="/w/index.php?title=Bovine_adrenal_medullary_peptide-18P&action=edit&redlink=1" class="new" title="Bovine adrenal medullary peptide-18P (page does not exist)">BAM-18P</a></li> <li><a href="/w/index.php?title=Bovine_adrenal_medullary_peptide-22P&action=edit&redlink=1" class="new" title="Bovine adrenal medullary peptide-22P (page does not exist)">BAM-22P</a></li> <li><a href="/wiki/Big_dynorphin" title="Big dynorphin">Big dynorphin</a></li> <li><a href="/wiki/Bremazocine" title="Bremazocine">Bremazocine</a></li> <li><a href="/wiki/BRL-52537" title="BRL-52537">BRL-52537</a></li> <li><a href="/wiki/Butorphan" class="mw-redirect" title="Butorphan">Butorphan</a></li> <li><a href="/wiki/Butorphanol" title="Butorphanol">Butorphanol</a></li> <li><a href="/wiki/BW373U86" title="BW373U86">BW373U86</a></li> <li><a href="/wiki/Cebranopadol" title="Cebranopadol">Cebranopadol</a></li> <li><a href="/wiki/Ciprefadol" title="Ciprefadol">Ciprefadol</a></li> <li><a href="/wiki/CR665" title="CR665">CR665</a></li> <li><a href="/wiki/Cyclazocine" title="Cyclazocine">Cyclazocine</a></li> <li><a href="/wiki/Cyclorphan" title="Cyclorphan">Cyclorphan</a></li> <li><a href="/wiki/Cyprenorphine" title="Cyprenorphine">Cyprenorphine</a></li> <li><a href="/wiki/Desmetramadol" title="Desmetramadol">Desmetramadol (desmethyltramadol)</a></li> <li><a href="/wiki/Heroin" title="Heroin">Diamorphine (heroin)</a></li> <li><a href="/wiki/Diacetylnalorphine" title="Diacetylnalorphine">Diacetylnalorphine</a></li> <li><a href="/wiki/Difelikefalin" title="Difelikefalin">Difelikefalin</a></li> <li><a href="/wiki/Dihydroetorphine" title="Dihydroetorphine">Dihydroetorphine</a></li> <li><a href="/wiki/Dihydromorphine" title="Dihydromorphine">Dihydromorphine</a></li> <li><a href="/wiki/Dinalbuphine_sebacate" title="Dinalbuphine sebacate">Dinalbuphine sebacate</a></li> <li><a href="/wiki/Diprenorphine" title="Diprenorphine">Diprenorphine</a></li> <li><a href="/wiki/Dynorphin_A" title="Dynorphin A">Dynorphin A</a></li> <li><a href="/wiki/Dynorphin_B" title="Dynorphin B">Dynorphin B (rimorphin)</a></li> <li><a href="/wiki/Eluxadoline" title="Eluxadoline">Eluxadoline</a></li> <li><a href="/wiki/Enadoline" title="Enadoline">Enadoline</a></li> <li><a href="/wiki/Eptazocine" title="Eptazocine">Eptazocine</a></li> <li><a href="/w/index.php?title=Erinacine_E&action=edit&redlink=1" class="new" title="Erinacine E (page does not exist)">Erinacine E</a></li> <li><a href="/wiki/Ethylketazocine" title="Ethylketazocine">Ethylketazocine</a></li> <li><a href="/wiki/Etorphine" title="Etorphine">Etorphine</a></li> <li><a href="/wiki/Fedotozine" title="Fedotozine">Fedotozine</a></li> <li><a href="/wiki/Fentanyl" title="Fentanyl">Fentanyl</a></li> <li><a href="/wiki/Gemazocine" title="Gemazocine">Gemazocine</a></li> <li><a href="/wiki/GR-89696" title="GR-89696">GR-89696</a></li> <li><a href="/w/index.php?title=GR-103545&action=edit&redlink=1" class="new" title="GR-103545 (page does not exist)">GR-103545</a></li> <li><a href="/wiki/Hemorphin-4" title="Hemorphin-4">Hemorphin-4</a></li> <li><a href="/wiki/Herkinorin" title="Herkinorin">Herkinorin</a></li> <li><a href="/wiki/HS665" title="HS665">HS665</a></li> <li><a href="/wiki/Hydromorphone" title="Hydromorphone">Hydromorphone</a></li> <li><a href="/wiki/HZ-2" title="HZ-2">HZ-2</a></li> <li><a href="/wiki/Ibogaine" title="Ibogaine">Ibogaine</a></li> <li><a href="/wiki/ICI-199,441" title="ICI-199,441">ICI-199,441</a></li> <li><a href="/wiki/ICI-204,448" title="ICI-204,448">ICI-204,448</a></li> <li><a href="/wiki/Ketamine" title="Ketamine">Ketamine</a></li> <li><a href="/wiki/Ketazocine" title="Ketazocine">Ketazocine</a></li> <li><a href="/wiki/Laudanosine" title="Laudanosine">Laudanosine</a></li> <li><a href="/wiki/Leumorphin" title="Leumorphin">Leumorphin (dynorphin B-29)</a></li> <li><a href="/wiki/Levallorphan" title="Levallorphan">Levallorphan</a></li> <li><a href="/wiki/Levomethorphan" title="Levomethorphan">Levomethorphan</a></li> <li><a href="/wiki/Levorphanol" title="Levorphanol">Levorphanol</a></li> <li><a href="/w/index.php?title=Lexanopadol&action=edit&redlink=1" class="new" title="Lexanopadol (page does not exist)">Lexanopadol</a></li> <li><a href="/wiki/Lofentanil" title="Lofentanil">Lofentanil</a></li> <li><a href="/wiki/LPK-26" title="LPK-26">LPK-26</a></li> <li><a href="/wiki/Lufuradom" title="Lufuradom">Lufuradom</a></li> <li><a href="/wiki/Matrine" title="Matrine">Matrine</a></li> <li><a href="/w/index.php?title=MB-1C-OH&action=edit&redlink=1" class="new" title="MB-1C-OH (page does not exist)">MB-1C-OH</a></li> <li><a href="/wiki/Menthol" title="Menthol">Menthol</a></li> <li><a href="/wiki/Metazocine" title="Metazocine">Metazocine</a></li> <li><a href="/wiki/Metkefamide" title="Metkefamide">Metkefamide</a></li> <li><a href="/wiki/Mianserin" title="Mianserin">Mianserin</a></li> <li><a href="/wiki/Mirtazapine" title="Mirtazapine">Mirtazapine</a></li> <li><a href="/wiki/Morphine" title="Morphine">Morphine</a></li> <li><a href="/wiki/Moxazocine" title="Moxazocine">Moxazocine</a></li> <li><a href="/w/index.php?title=MR-2034&action=edit&redlink=1" class="new" title="MR-2034 (page does not exist)">MR-2034</a></li> <li><a href="/w/index.php?title=N-MPPP&action=edit&redlink=1" class="new" title="N-MPPP (page does not exist)">N-MPPP</a></li> <li><a href="/wiki/Nalbuphine" title="Nalbuphine">Nalbuphine</a></li> <li><a href="/w/index.php?title=Naloxone_benzoylhydrazone&action=edit&redlink=1" class="new" title="Naloxone benzoylhydrazone (page does not exist)">NalBzOH</a></li> <li><a href="/wiki/Nalfurafine" title="Nalfurafine">Nalfurafine</a></li> <li><a href="/wiki/Nalmefene" title="Nalmefene">Nalmefene</a></li> <li><a href="/wiki/Nalodeine" title="Nalodeine">Nalodeine (N-allylnorcodeine)</a></li> <li><a href="/wiki/Nalorphine" title="Nalorphine">Nalorphine</a></li> <li><a href="/wiki/Naltriben" title="Naltriben">Naltriben</a></li> <li><a href="/wiki/Niravoline" title="Niravoline">Niravoline</a></li> <li><a href="/wiki/Norbuprenorphine" title="Norbuprenorphine">Norbuprenorphine</a></li> <li><a href="/wiki/Norbuprenorphine-3-glucuronide" title="Norbuprenorphine-3-glucuronide">Norbuprenorphine-3-glucuronide</a></li> <li><a href="/wiki/Noribogaine" title="Noribogaine">Noribogaine</a></li> <li><a href="/wiki/Norketamine" title="Norketamine">Norketamine</a></li> <li><a href="/wiki/Oripavine" title="Oripavine">Oripavine</a></li> <li><a href="/wiki/Oxilorphan" title="Oxilorphan">Oxilorphan</a></li> <li><a href="/wiki/Oxycodone" title="Oxycodone">Oxycodone</a></li> <li><a href="/wiki/Pentazocine" title="Pentazocine">Pentazocine</a></li> <li><a href="/wiki/Pethidine" title="Pethidine">Pethidine (meperidine)</a></li> <li><a href="/wiki/Phenazocine" title="Phenazocine">Phenazocine</a></li> <li><a href="/wiki/Proxorphan" title="Proxorphan">Proxorphan</a></li> <li><a href="/wiki/Methorphan" title="Methorphan">Racemethorphan</a></li> <li><a href="/wiki/Racemorphan" title="Racemorphan">Racemorphan</a></li> <li><a href="/wiki/RB-64" title="RB-64">RB-64</a></li> <li><a href="/wiki/Salvinorin_A" title="Salvinorin A">Salvinorin A</a> (<a href="/wiki/Salvia_divinorum" title="Salvia divinorum">salvia</a>)</li> <li><a href="/wiki/Salvinorin_B_ethoxymethyl_ether" class="mw-redirect" title="Salvinorin B ethoxymethyl ether">Salvinorin B ethoxymethyl ether</a></li> <li><a href="/wiki/Salvinorin_B_methoxymethyl_ether" title="Salvinorin B methoxymethyl ether">Salvinorin B methoxymethyl ether</a></li> <li><a href="/wiki/Samidorphan" title="Samidorphan">Samidorphan</a></li> <li><a href="/wiki/Spiradoline" title="Spiradoline">Spiradoline (U-62,066)</a></li> <li><a href="/wiki/TH-030418" title="TH-030418">TH-030418</a></li> <li><a href="/wiki/Thienorphine" title="Thienorphine">Thienorphine</a></li> <li><a href="/wiki/Tifluadom" title="Tifluadom">Tifluadom</a></li> <li><a href="/wiki/Tricyclic_antidepressant" title="Tricyclic antidepressant">Tricyclic antidepressants</a> (e.g., <a href="/wiki/Amitriptyline" title="Amitriptyline">amitriptyline</a>, <a href="/wiki/Desipramine" title="Desipramine">desipramine</a>, <a href="/wiki/Imipramine" title="Imipramine">imipramine</a>, <a href="/wiki/Nortriptyline" title="Nortriptyline">nortriptyline</a>)</li> <li><a href="/wiki/U-50488" title="U-50488">U-50488</a></li> <li><a href="/w/index.php?title=U-54,494A&action=edit&redlink=1" class="new" title="U-54,494A (page does not exist)">U-54,494A</a></li> <li><a href="/wiki/U-69,593" title="U-69,593">U-69,593</a></li> <li><a href="/wiki/Xorphanol" title="Xorphanol">Xorphanol</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%">Antagonists</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/4%E2%80%B2-Hydroxyflavanone" class="mw-redirect" title="4′-Hydroxyflavanone">4′-Hydroxyflavanone</a></li> <li><a href="/wiki/4%27,7-Dihydroxyflavone" title="4',7-Dihydroxyflavone">4',7-Dihydroxyflavone</a></li> <li><a href="/wiki/5%27-Guanidinonaltrindole" title="5'-Guanidinonaltrindole">5'-GNTI</a></li> <li><a href="/wiki/6%27-Guanidinonaltrindole" title="6'-Guanidinonaltrindole">6'-GNTI</a></li> <li><a href="/wiki/6%CE%B2-Naltrexol" title="6β-Naltrexol">6β-Naltrexol</a></li> <li><a href="/wiki/6%CE%B2-Naltrexol-d4" title="6β-Naltrexol-d4">6β-Naltrexol-d4</a></li> <li><a href="/wiki/Chlornaltrexamine" class="mw-redirect" title="Chlornaltrexamine">β-Chlornaltrexamine</a></li> <li><a href="/wiki/Buprenorphine/samidorphan" title="Buprenorphine/samidorphan">Buprenorphine/samidorphan</a></li> <li><a href="/wiki/Amentoflavone" title="Amentoflavone">Amentoflavone</a></li> <li><a href="/w/index.php?title=5%27-Acetamidinoethylnaltrindole&action=edit&redlink=1" class="new" title="5'-Acetamidinoethylnaltrindole (page does not exist)">ANTI</a></li> <li><a href="/wiki/Apigenin" title="Apigenin">Apigenin</a></li> <li><a href="/w/index.php?title=Arodyne&action=edit&redlink=1" class="new" title="Arodyne (page does not exist)">Arodyne</a></li> <li><a href="/wiki/AT-076" title="AT-076">AT-076</a></li> <li><a href="/wiki/Aticaprant" title="Aticaprant">Aticaprant</a></li> <li><a href="/wiki/Axelopran" title="Axelopran">Axelopran</a></li> <li><a href="/w/index.php?title=AZ-MTAB&action=edit&redlink=1" class="new" title="AZ-MTAB (page does not exist)">AZ-MTAB</a></li> <li><a href="/wiki/Binaltorphimine" title="Binaltorphimine">Binaltorphimine</a></li> <li><a href="/wiki/BU09059" title="BU09059">BU09059</a></li> <li><a href="/wiki/Buprenorphine" title="Buprenorphine">Buprenorphine</a></li> <li><a href="/wiki/Catechin" title="Catechin">Catechin</a></li> <li><a href="/wiki/Epicatechin_gallate" title="Epicatechin gallate">Catechin gallate</a></li> <li><a href="/wiki/CERC-501" class="mw-redirect" title="CERC-501">CERC-501 (LY-2456302)</a></li> <li><a href="/wiki/Clocinnamox" title="Clocinnamox">Clocinnamox</a></li> <li><a href="/wiki/Icalcaprant" title="Icalcaprant">CVL-354</a></li> <li><a href="/w/index.php?title=Cyclofoxy&action=edit&redlink=1" class="new" title="Cyclofoxy (page does not exist)">Cyclofoxy</a></li> <li><a href="/wiki/Dezocine" title="Dezocine">Dezocine</a></li> <li><a href="/w/index.php?title=DIPPA&action=edit&redlink=1" class="new" title="DIPPA (page does not exist)">DIPPA</a></li> <li><a href="/wiki/Gallocatechol" title="Gallocatechol">EGC</a></li> <li><a href="/wiki/Epicatechin_gallate" title="Epicatechin gallate">ECG</a></li> <li><a href="/wiki/Epicatechin" class="mw-redirect" title="Epicatechin">Epicatechin</a></li> <li><a href="/wiki/Hyperoside" title="Hyperoside">Hyperoside</a></li> <li><a href="/wiki/JDTic" title="JDTic">JDTic</a></li> <li><a href="/wiki/LY-255582" title="LY-255582">LY-255582</a></li> <li><a href="/wiki/LY-2196044" class="mw-redirect" title="LY-2196044">LY-2196044</a></li> <li><a href="/w/index.php?title=LY-2444296&action=edit&redlink=1" class="new" title="LY-2444296 (page does not exist)">LY-2444296</a></li> <li><a href="/wiki/LY-2459989" title="LY-2459989">LY-2459989</a></li> <li><a href="/w/index.php?title=LY-2795050&action=edit&redlink=1" class="new" title="LY-2795050 (page does not exist)">LY-2795050</a></li> <li><a href="/w/index.php?title=MeJDTic&action=edit&redlink=1" class="new" title="MeJDTic (page does not exist)">MeJDTic</a></li> <li><a href="/wiki/Methylnaltrexone" title="Methylnaltrexone">Methylnaltrexone</a></li> <li><a href="/w/index.php?title=ML190&action=edit&redlink=1" class="new" title="ML190 (page does not exist)">ML190</a></li> <li><a href="/w/index.php?title=ML350&action=edit&redlink=1" class="new" title="ML350 (page does not exist)">ML350</a></li> <li><a href="/w/index.php?title=MR-2266&action=edit&redlink=1" class="new" title="MR-2266 (page does not exist)">MR-2266</a></li> <li><a href="/w/index.php?title=N-Fluoropropyl-JDTic&action=edit&redlink=1" class="new" title="N-Fluoropropyl-JDTic (page does not exist)">N-Fluoropropyl-JDTic</a></li> <li><a href="/wiki/Naloxone" title="Naloxone">Naloxone</a></li> <li><a href="/wiki/Naltrexone" title="Naltrexone">Naltrexone</a></li> <li><a href="/wiki/Naltrindole" title="Naltrindole">Naltrindole</a></li> <li><a href="/wiki/Naringenin" title="Naringenin">Naringenin</a></li> <li><a href="/wiki/Navacaprant" title="Navacaprant">Navacaprant</a></li> <li><a href="/wiki/Norbinaltorphimine" title="Norbinaltorphimine">Norbinaltorphimine</a></li> <li><a href="/wiki/Noribogaine" title="Noribogaine">Noribogaine</a></li> <li><a href="/wiki/Pawhuskin_A" title="Pawhuskin A">Pawhuskin A</a></li> <li><a href="/wiki/PF-4455242" class="mw-redirect" title="PF-4455242">PF-4455242</a></li> <li><a href="/wiki/RB-64" title="RB-64">RB-64</a></li> <li><a href="/wiki/Quadazocine" title="Quadazocine">Quadazocine</a></li> <li><a href="/wiki/Taxifolin" title="Taxifolin">Taxifolin</a></li> <li><a href="/w/index.php?title=UPHIT&action=edit&redlink=1" class="new" title="UPHIT (page does not exist)">UPHIT</a></li> <li><a href="/wiki/Zyklophin" title="Zyklophin">Zyklophin</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/Nociceptin_receptor" title="Nociceptin receptor">Nociceptin</a><br />(NOP)</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%">Agonists</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="/w/index.php?title=(Arg14,Lys15)Nociceptin&action=edit&redlink=1" class="new" title="(Arg14,Lys15)Nociceptin (page does not exist)">(Arg14,Lys15)Nociceptin</a></li> <li><a href="/w/index.php?title=((pF)Phe4)Nociceptin(1-13)NH2&action=edit&redlink=1" class="new" title="((pF)Phe4)Nociceptin(1-13)NH2 (page does not exist)">((pF)Phe<sup>4</sup>)Nociceptin(1-13)NH<sub>2</sub></a></li> <li><a href="/w/index.php?title=(Phe1%CE%A8(CH2-NH)Gly2)Nociceptin(1-13)NH2&action=edit&redlink=1" class="new" title="(Phe1Ψ(CH2-NH)Gly2)Nociceptin(1-13)NH2 (page does not exist)">(Phe<sup>1</sup>Ψ(CH<sub>2</sub>-NH)Gly<sup>2</sup>)Nociceptin(1-13)NH<sub>2</sub></a></li> <li><a href="/w/index.php?title=Ac-RYYRWK-NH2&action=edit&redlink=1" class="new" title="Ac-RYYRWK-NH2 (page does not exist)">Ac-RYYRWK-NH<sub>2</sub></a></li> <li><a href="/w/index.php?title=Ac-RYYRIK-NH2&action=edit&redlink=1" class="new" title="Ac-RYYRIK-NH2 (page does not exist)">Ac-RYYRIK-NH<sub>2</sub></a></li> <li><a href="/w/index.php?title=BU08070&action=edit&redlink=1" class="new" title="BU08070 (page does not exist)">BU08070</a></li> <li><a href="/wiki/Buprenorphine" title="Buprenorphine">Buprenorphine</a></li> <li><a href="/wiki/Cebranopadol" title="Cebranopadol">Cebranopadol</a></li> <li><a href="/wiki/Dihydroetorphine" title="Dihydroetorphine">Dihydroetorphine</a></li> <li><a href="/wiki/Etorphine" title="Etorphine">Etorphine</a></li> <li><a href="/w/index.php?title=JNJ-19385899&action=edit&redlink=1" class="new" title="JNJ-19385899 (page does not exist)">JNJ-19385899</a></li> <li><a href="/wiki/Levomethorphan" title="Levomethorphan">Levomethorphan</a></li> <li><a href="/wiki/Levorphanol" title="Levorphanol">Levorphanol</a></li> <li><a href="/w/index.php?title=Lexanopadol&action=edit&redlink=1" class="new" title="Lexanopadol (page does not exist)">Lexanopadol</a></li> <li><a href="/wiki/MCOPPB" title="MCOPPB">MCOPPB</a></li> <li><a href="/wiki/MT-7716" title="MT-7716">MT-7716</a></li> <li><a href="/wiki/NNC_63-0532" title="NNC 63-0532">NNC 63-0532</a></li> <li><a href="/wiki/Nociceptin" title="Nociceptin">Nociceptin (orphanin FQ)</a></li> <li><a href="/w/index.php?title=Nociceptin_(1-11)&action=edit&redlink=1" class="new" title="Nociceptin (1-11) (page does not exist)">Nociceptin (1-11)</a></li> <li><a href="/w/index.php?title=Nociceptin_(1-13)NH2&action=edit&redlink=1" class="new" title="Nociceptin (1-13)NH2 (page does not exist)">Nociceptin (1-13)NH<sub>2</sub></a></li> <li><a href="/wiki/Norbuprenorphine" title="Norbuprenorphine">Norbuprenorphine</a></li> <li><a href="/wiki/Methorphan" title="Methorphan">Racemethorphan</a></li> <li><a href="/wiki/Racemorphan" title="Racemorphan">Racemorphan</a></li> <li><a href="/wiki/Ro64-6198" title="Ro64-6198">Ro64-6198</a></li> <li><a href="/wiki/Ro65-6570" title="Ro65-6570">Ro65-6570</a></li> <li><a href="/wiki/SCH-221510" title="SCH-221510">SCH-221510</a></li> <li><a href="/w/index.php?title=SCH-486757&action=edit&redlink=1" class="new" title="SCH-486757 (page does not exist)">SCH-486757</a></li> <li><a href="/w/index.php?title=SR-8993&action=edit&redlink=1" class="new" title="SR-8993 (page does not exist)">SR-8993</a></li> <li><a href="/wiki/SR-16435" title="SR-16435">SR-16435</a></li> <li><a href="/wiki/Sunobinop" title="Sunobinop">Sunobinop (S-117957)</a></li> <li><a href="/wiki/TH-030418" title="TH-030418">TH-030418</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%">Antagonists</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="/w/index.php?title=(Nphe1)Nociceptin(1-13)NH2&action=edit&redlink=1" class="new" title="(Nphe1)Nociceptin(1-13)NH2 (page does not exist)">(Nphe<sup>1</sup>)Nociceptin(1-13)NH<sub>2</sub></a></li> <li><a href="/wiki/AT-076" title="AT-076">AT-076</a></li> <li><a href="/w/index.php?title=BAN-ORL-24&action=edit&redlink=1" class="new" title="BAN-ORL-24 (page does not exist)">BAN-ORL-24</a></li> <li><a href="/wiki/BTRX-246040" title="BTRX-246040">BTRX-246040 (LY-2940094)</a></li> <li><a href="/wiki/J-113,397" title="J-113,397">J-113,397</a></li> <li><a href="/wiki/JTC-801" title="JTC-801">JTC-801</a></li> <li><a href="/w/index.php?title=Naloxone_benzoylhydrazone&action=edit&redlink=1" class="new" title="Naloxone benzoylhydrazone (page does not exist)">NalBzOH</a></li> <li><a href="/w/index.php?title=Nociceptin_(1-7)&action=edit&redlink=1" class="new" title="Nociceptin (1-7) (page does not exist)">Nociceptin (1-7)</a></li> <li><a href="/w/index.php?title=Nocistatin&action=edit&redlink=1" class="new" title="Nocistatin (page does not exist)">Nocistatin</a></li> <li><a href="/wiki/SB-612,111" title="SB-612,111">SB-612,111</a></li> <li><a href="/w/index.php?title=SR-16430&action=edit&redlink=1" class="new" title="SR-16430 (page does not exist)">SR-16430</a></li> <li><a href="/wiki/Thienorphine" title="Thienorphine">Thienorphine</a></li> <li><a href="/w/index.php?title=Trap-101&action=edit&redlink=1" class="new" title="Trap-101 (page does not exist)">Trap-101</a></li> <li><a href="/w/index.php?title=UFP-101&action=edit&redlink=1" class="new" title="UFP-101 (page does not exist)">UFP-101</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;">Others</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><i><a href="/wiki/Enkephalinase_inhibitor" title="Enkephalinase inhibitor">Enkephalinase inhibitors</a>:</i> <a href="/wiki/Amastatin" title="Amastatin">Amastatin</a></li> <li><a href="/w/index.php?title=BL-2401&action=edit&redlink=1" class="new" title="BL-2401 (page does not exist)">BL-2401</a></li> <li><a href="/wiki/Candoxatril" title="Candoxatril">Candoxatril</a></li> <li><a href="/wiki/Phenylalanine#D-,_L-_and_DL-phenylalanine" title="Phenylalanine"><span style="font-size:85%;">D </span>-Phenylalanine</a></li> <li><a href="/w/index.php?title=Dexecadotril&action=edit&redlink=1" class="new" title="Dexecadotril (page does not exist)">Dexecadotril (retorphan)</a></li> <li><a href="/wiki/Ecadotril" title="Ecadotril">Ecadotril (sinorphan)</a></li> <li><a href="/wiki/Kelatorphan" title="Kelatorphan">Kelatorphan</a></li> <li><a href="/wiki/Racecadotril" title="Racecadotril">Racecadotril (acetorphan)</a></li> <li><a href="/wiki/RB-101" title="RB-101">RB-101</a></li> <li><a href="/wiki/RB-120" title="RB-120">RB-120</a></li> <li><a href="/wiki/RB-3007" title="RB-3007">RB-3007</a></li> <li><a href="/w/index.php?title=Opiorphan&action=edit&redlink=1" class="new" title="Opiorphan (page does not exist)">Opiorphan</a></li> <li><a href="/wiki/Selank" title="Selank">Selank</a></li> <li><a href="/wiki/Semax" title="Semax">Semax</a></li> <li><a href="/wiki/Spinorphin" title="Spinorphin">Spinorphin</a></li> <li><a href="/wiki/Thiorphan" title="Thiorphan">Thiorphan</a></li> <li><a href="/wiki/Tynorphin" title="Tynorphin">Tynorphin</a></li> <li><a href="/wiki/Ubenimex" title="Ubenimex">Ubenimex (bestatin)</a></li></ul> <ul><li><i>Propeptides:</i> <a href="/wiki/Lipotropin" title="Lipotropin">β-Lipotropin (proendorphin)</a></li> <li><a href="/wiki/Prodynorphin" title="Prodynorphin">Prodynorphin</a></li> <li><a href="/wiki/Proenkephalin" title="Proenkephalin">Proenkephalin</a></li> <li><a href="/w/index.php?title=Pronociceptin&action=edit&redlink=1" class="new" title="Pronociceptin (page does not exist)">Pronociceptin</a></li> <li><a href="/wiki/Proopiomelanocortin" title="Proopiomelanocortin">Proopiomelanocortin (POMC)</a></li></ul> <ul><li><i>Others:</i> <a href="/wiki/Kyotorphin" title="Kyotorphin">Kyotorphin</a> (met-enkephalin releaser/degradation stabilizer)</li></ul> </div></td></tr></tbody></table></div> <style data-mw-deduplicate="TemplateStyles:r1130092004">.mw-parser-output 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