# Dextrorphan > Mediated Wiki article. Canonical URL: https://mediated.wiki/source/Dextrorphan > Markdown URL: https://mediated.wiki/source/Dextrorphan.md > Source: https://en.wikipedia.org/wiki/Dextrorphan > Source revision: 1351187251 > License: Creative Commons Attribution-ShareAlike 4.0 International (https://creativecommons.org/licenses/by-sa/4.0/) {{Short description|Psychoactive cough suppressant medication}} {{Distinguish|Dextromethorphan|Dextrallorphan}} {{Infobox drug | Verifiedfields = changed | Watchedfields = changed | class = [Cough suppressant](/source/Cough_suppressant); [NMDA receptor antagonist](/source/NMDA_receptor_antagonist); [Serotonin-norepinephrine reuptake inhibitor](/source/Serotonin-norepinephrine_reuptake_inhibitor); [Dissociative hallucinogen](/source/Dissociative_hallucinogen) | verifiedrevid = 408496712 | IUPAC_name = (+)-17-methyl-9a,13a,14a-morphinan-3-ol | image = Dextrorphan.svg | image_class = skin-invert-image | tradename = | legal_US = Unscheduled{{Cite web |last=Bensinger |first=Peter |date=October 1, 1976 |title=Dextrophan and Nalbuphine; Removal from Schedules |url=https://www.govinfo.gov/content/pkg/FR-1976-10-01/pdf/FR-1976-10-01.pdf |access-date=June 26, 2023 |website=[NARA](/source/NARA)}} | CAS_number_Ref = {{cascite|correct|??}} | CAS_number = 125-73-5 | ATC_prefix = None | PubChem = 5360697 | UNII_Ref = {{fdacite|changed|FDA}} | UNII = 04B7QNO9WS | ChEMBL_Ref = {{ebicite|changed|EBI}} | ChEMBL = 1254766 | ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}} | ChemSpiderID = 10489895 | synonyms = DXO, Dextrorphanol | C = 17 | H = 23 | N = 1 | O = 1 | SMILES = CN1CC[C@@]23CCCC[C@@H]2[C@@H]1Cc4c3cc(O)cc4 | StdInChI_Ref = {{stdinchicite|changed|chemspider}} | StdInChI = 1S/C17H23NO/c1-18-9-8-17-7-3-2-4-14(17)16(18)10-12-5-6-13(19)11-15(12)17/h5-6,11,14,16,19H,2-4,7-10H2,1H3/t14-,16+,17+/m1/s1 | StdInChIKey_Ref = {{stdinchicite|changed|chemspider}} | StdInChIKey = JAQUASYNZVUNQP-PVAVHDDUSA-N }} '''Dextrorphan''' ('''DXO''') is a [psychoactive drug](/source/psychoactive_drug) of the [morphinan](/source/morphinan) class which acts as an [antitussive](/source/antitussive) or [cough suppressant](/source/cough_suppressant) and in high doses a [dissociative](/source/dissociative_drug) [hallucinogen](/source/hallucinogen). It is the [dextrorotatory](/source/dextrorotatory) [enantiomer](/source/enantiomer) of [racemorphan](/source/racemorphan); the [levorotatory](/source/Levorotation) enantiomer is [levorphanol](/source/levorphanol). Dextrorphan is produced by O-demethylation of [dextromethorphan](/source/dextromethorphan) by [CYP2D6](/source/CYP2D6). Dextrorphan is an [NMDA antagonist](/source/NMDA_receptor_antagonist) and contributes to the psychoactive effects of dextromethorphan.{{cite journal | vauthors = Zawertailo LA, Kaplan HL, Busto UE, Tyndale RF, Sellers EM | title = Psychotropic effects of dextromethorphan are altered by the CYP2D6 polymorphism: a pilot study | journal = Journal of Clinical Psychopharmacology | volume = 18 | issue = 4 | pages = 332–337 | date = August 1998 | pmid = 9690700 | doi = 10.1097/00004714-199808000-00014 }} ==Pharmacology== ===Pharmacodynamics=== {| class="wikitable floatleft" style="font-size:small;" |+ Dextrorphan{{cite web | title = PDSP Ki Database | work = Psychoactive Drug Screening Program (PDSP)|author1-link=Bryan Roth| vauthors = Roth BL, Driscol J | publisher = University of North Carolina at Chapel Hill and the United States National Institute of Mental Health | access-date = 14 August 2017 | url = https://pdsp.unc.edu/databases/pdsp.php?knowID=0&kiKey=&receptorDD=&receptor=&speciesDD=&species=&sourcesDD=&source=&hotLigandDD=&hotLigand=&testLigandDD=&testFreeRadio=testFreeRadio&testLigand=dextrorphan&referenceDD=&reference=&KiGreater=&KiLess=&kiAllRadio=all&doQuery=Submit+Query}}{{cite journal | vauthors = Nguyen L, Thomas KL, Lucke-Wold BP, Cavendish JZ, Crowe MS, Matsumoto RR | title = Dextromethorphan: An update on its utility for neurological and neuropsychiatric disorders | journal = Pharmacol. Ther. | volume = 159 | pages = 1–22 | year = 2016 | pmid = 26826604 | doi = 10.1016/j.pharmthera.2016.01.016 | doi-access = free }}{{cite journal | vauthors = Werling LL, Keller A, Frank JG, Nuwayhid SJ | title = A comparison of the binding profiles of dextromethorphan, memantine, fluoxetine and amitriptyline: treatment of involuntary emotional expression disorder | journal = Exp. Neurol. | volume = 207 | issue = 2 | pages = 248–57 | year = 2007 | pmid = 17689532 | doi = 10.1016/j.expneurol.2007.06.013 | s2cid = 38476281 }}{{cite journal | vauthors = Taylor CP, Traynelis SF, Siffert J, Pope LE, Matsumoto RR | title = Pharmacology of dextromethorphan: Relevance to dextromethorphan/quinidine (Nuedexta®) clinical use | journal = Pharmacol. Ther. | volume = 164 | pages = 170–82 | year = 2016 | pmid = 27139517 | doi = 10.1016/j.pharmthera.2016.04.010 | doi-access = free }} |- ! Site !! Ki (nM) !! Species !! Ref |- | [{{abbr|NMDAR|N-Methyl-D-aspartate receptor}}
(MK-801)](/source/NMDA_receptor) || 486–906 || Rat || |- | [σ1](/source/Sigma-1_receptor) || 118–481 || Rat || |- | [σ2](/source/Sigma-2_receptor) || 11,325–15,582 || Rat || |- | {{abbrlink|MOR|μ-Opioid receptor}} || 420
>1,000 || Rat
Human || {{cite journal | vauthors = Raynor K, Kong H, Mestek A, Bye LS, Tian M, Liu J, Yu L, Reisine T | title = Characterization of the cloned human mu opioid receptor | journal = J. Pharmacol. Exp. Ther. | volume = 272 | issue = 1 | pages = 423–8 | year = 1995 | doi = 10.1016/S0022-3565(25)24351-8 | pmid = 7815359 }} |- | {{abbrlink|DOR|δ-Opioid receptor}} || 34,700 || Rat || |- | {{abbrlink|KOR|κ-Opioid receptor}} || 5,950 || Rat || |- | {{abbrlink|SERT|Serotonin transporter}} || 401–484 || Rat || |- | {{abbrlink|NET|Norepinephrine transporter}} || ≥340 || Rat || |- | {{abbrlink|DAT|Dopamine transporter}} || >1,000 || Rat || |- | [5-HT1A](/source/5-HT1A_receptor) || >1,000 || Rat || |- | [5-HT1B](/source/5-HT1B_receptor)/[1D](/source/5-HT1D_receptor) || 54% at 1 μM || Rat || |- | [5-HT2A](/source/5-HT2A_receptor) || >1,000 || Rat || |- | [α1](/source/Alpha-1_adrenergic_receptor) ||>1,000 || Rat || |- | [α2](/source/Alpha-2_adrenergic_receptor) || >1,000 || Rat || |- | [β](/source/Beta-adrenergic_receptor) || 35% at 1 μM || Rat || |- | [D2](/source/D2_receptor) || >1,000 || Rat || |- | [H1](/source/H1_receptor) || 95% at 1 μM || Rat || |- | {{abbrlink|mAChRs|Muscarinic acetylcholine receptors}} || 100% at 1 μM || Rat || |- | {{abbrlink|nAChRs|Nicotinic acetylcholine receptors}} || 1,300–29,600
(IC50) || Rat || |- | {{abbrlink|VDSCs|Voltage-dependent sodium channels}} || {{abbr|ND|No data}} || {{abbr|ND|No data}} || {{abbr|ND|No data}} |- class="sortbottom" | colspan="4" style="width: 1px;" | Values are Ki (nM), unless otherwise noted. The smaller the value, the more strongly the drug binds to the site. |} The pharmacology of dextrorphan is similar to that of [dextromethorphan](/source/dextromethorphan) (DXM). However, dextrorphan is much more potent as an NMDA receptor antagonist and much less active as a [serotonin reuptake inhibitor](/source/serotonin_reuptake_inhibitor), but retains DXM's activity as a [norepinephrine reuptake inhibitor](/source/norepinephrine_reuptake_inhibitor).{{cite journal | vauthors = Pechnick RN, Poland RE | title = Comparison of the effects of dextromethorphan, dextrorphan, and levorphanol on the hypothalamo-pituitary-adrenal axis | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 309 | issue = 2 | pages = 515–522 | date = May 2004 | pmid = 14742749 | doi = 10.1124/jpet.103.060038 | s2cid = 274504 }} It also has more affinity for the opioid receptors than dextromethorphan, significantly so at high doses. ===Pharmacokinetics=== Dextrorphan has a notably longer [elimination half-life](/source/elimination_half-life) than its parent compound, and therefore has a tendency to accumulate in the blood after repeated administration of normally dosed dextromethorphan formulations.{{citation needed|date=November 2016}} It is further converted to [3-HM](/source/3-Hydroxymorphinan) by [CYP3A4](/source/CYP3A4) or [glucuronidated](/source/glucuronidation).{{cite journal | vauthors = Yu A, Haining RL | title = Comparative contribution to dextromethorphan metabolism by cytochrome P450 isoforms in vitro: can dextromethorphan be used as a dual probe for both CTP2D6 and CYP3A activities? | journal = Drug Metabolism and Disposition | volume = 29 | issue = 11 | pages = 1514–20 | date = November 2001 | pmid = 11602530 | url = http://dmd.aspetjournals.org/cgi/pmidlookup?view=long&pmid=11602530 | archive-date = 2020-03-12 | access-date = 2021-04-22 | archive-url = https://web.archive.org/web/20200312134718/http://dmd.aspetjournals.org/content/29/11/1514.long | url-status = dead }} ==Society and culture== ===Legal status=== Dextrorphan was formerly a [Schedule I](/source/Controlled_Substances_Act) [controlled substance](/source/controlled_substance) in the [United States](/source/United_States), but was unscheduled on October 1, 1976.{{cite web | url = http://www.deadiversion.usdoj.gov/schedules/orangebook/orangebook.pdf | title = Lists of: Scheduling Actions Controlled Substances Regulated Chemicals | author = DEA | access-date = 2010-09-24 | archive-date = 2016-04-17 | archive-url = https://web.archive.org/web/20160417085648/http://www.deadiversion.usdoj.gov/schedules/orangebook/orangebook.pdf | url-status = dead }} ==Research== Dextrorphan was under development for the treatment of [stroke](/source/stroke), and reached [phase II](/source/Phases_of_clinical_research) [clinical trial](/source/clinical_trial)s for this indication, but development was discontinued.{{Cite web|url=https://adisinsight.springer.com/drugs/800009336|title = Dextrorphan - AdisInsight}} ==Environmental presence== In 2021, dextrorphan was identified in >75% of sludge samples taken from 12 [wastewater treatment](/source/wastewater_treatment) plants in [California](/source/California). The same study associated dextrorphan with [estrogenic](/source/estrogenic) activity by using [predictive modelling](/source/predictive_modelling), before observing it in [in vitro](/source/in_vitro).{{cite journal | vauthors = Black GP, He G, Denison MS, Young TM | title = Using Estrogenic Activity and Nontargeted Chemical Analysis to Identify Contaminants in Sewage Sludge | journal = Environmental Science & Technology | volume = 55 | issue = 10 | pages = 6729–6739 | date = May 2021 | pmid = 33909413 | pmc = 8378343 | doi = 10.1021/acs.est.0c07846 | bibcode = 2021EnST...55.6729B }} {{Clear}} == See also == * [Cough syrup](/source/Cough_syrup) * [Racemorphan](/source/Racemorphan); [Levorphanol](/source/Levorphanol) * [Noscapine](/source/Noscapine) * [Codeine](/source/Codeine); [Pholcodine](/source/Pholcodine) * [Dextromethorphan](/source/Dextromethorphan); [Dimemorfan](/source/Dimemorfan) * [Butamirate](/source/Butamirate) * [Pentoxyverine](/source/Pentoxyverine) * [Tipepidine](/source/Tipepidine) * [Cloperastine](/source/Cloperastine) ==References== {{Reflist|2}} {{Antitussives}} {{Navboxes | title = [Recreational uses](/source/Recreational_drug_use) | titlestyle = background:#ccccff | list1 = {{Drug use}} {{Dissociatives}} }} {{Navboxes | title = [Pharmacodynamics](/source/Pharmacodynamics) | titlestyle = background:#ccccff | list1 = {{Ionotropic glutamate receptor modulators}} {{Monoamine reuptake inhibitors}} {{Nicotinic acetylcholine receptor modulators}} {{Opioid receptor modulators}} {{Sigma receptor modulators}} }} Category:Antitussives Category:Dissociative drugs Category:Enantiopure drugs Category:Euphoriants Category:Morphinans Category:Mu-opioid receptor agonists Category:Nicotinic antagonists Category:NMDA receptor antagonists Category:Hydroxyarenes Category:Serotonin–norepinephrine reuptake inhibitors Category:Sigma agonists Category:Human drug metabolites Category:Recreational drug metabolites --- Adapted from the Wikipedia article [Dextrorphan](https://en.wikipedia.org/wiki/Dextrorphan) by Wikipedia contributors ([contributor history](https://en.wikipedia.org/wiki/Dextrorphan?action=history)). Available under [Creative Commons Attribution-ShareAlike 4.0 International](https://creativecommons.org/licenses/by-sa/4.0/). Changes may have been made.