Dextrorphan
{{Short description|Psychoactive cough suppressant medication}}
{{Distinguish|Dextromethorphan|Dextrallorphan}}
{{Infobox drug
| Verifiedfields = changed
| Watchedfields = changed
| verifiedrevid = 408496712
| IUPAC_name = (+)-17-methyl-9a,13a,14a-morphinan-3-ol
| image = Dextrorphan.svg
| image_class = skin-invert-image
| image2 = Dextrorphane 3d.gif
| 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}}
| 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 of the morphinan class which acts as an antitussive or cough suppressant and in high doses a dissociative hallucinogen. It is the dextrorotatory enantiomer of racemorphan; the levorotatory enantiomer is levorphanol. Dextrorphan is produced by O-demethylation of dextromethorphan by CYP2D6. Dextrorphan is an NMDA 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=
The pharmacology of dextrorphan is similar to that of dextromethorphan (DXM). However, dextrorphan is much more potent as an NMDA receptor antagonist and much less active as a serotonin reuptake inhibitor, but retains DXM's activity as a 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 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 by CYP3A4 or glucuronidated.{{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 }}
Society and culture
=Legal status=
Dextrorphan was formerly a Schedule I controlled substance in the 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, and reached phase II clinical trials for this indication, but development was discontinued.{{Cite web|url=http://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 plants in California. The same study associated dextrorphan with estrogenic activity by using predictive modelling, before observing it in 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
References
{{Reflist|2}}
{{Antitussives}}
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Category:Mu-opioid receptor agonists
Category:Nicotinic antagonists
Category:NMDA receptor antagonists