Dextrorphan

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Psychoactive cough suppressant medication

title: "Dextrorphan" type: doc version: 1 created: 2026-02-28 author: "Wikipedia contributors" status: active scope: public tags: ["antitussives", "dissociative-drugs", "enantiopure-drugs", "euphoriants", "morphinans", "mu-opioid-receptor-agonists", "nicotinic-antagonists", "nmda-receptor-antagonists", "hydroxyarenes", "serotonin–norepinephrine-reuptake-inhibitors", "sigma-agonists", "human-drug-metabolites", "recreational-drug-metabolites"] description: "Psychoactive cough suppressant medication" topic_path: "general/antitussives" source: "https://en.wikipedia.org/wiki/Dextrorphan" license: "CC BY-SA 4.0" wikipedia_page_id: 0 wikipedia_revision_id: 0

::summary Psychoactive cough suppressant medication ::

::data[format=table title="Infobox drug"]

Field	Value
Verifiedfields	changed
Watchedfields	changed
verifiedrevid	408496712
IUPAC_name	(+)-17-methyl-9a,13a,14a-morphinan-3-ol
image	Dextrorphan.svg
image_class	skin-invert-image
legal_US	Unscheduled
	CAS_number_Ref
CAS_number	125-73-5
ATC_prefix	None
PubChem	5360697
UNII_Ref
UNII	04B7QNO9WS
ChEMBL_Ref
ChEMBL	1254766
ChemSpiderID_Ref
ChemSpiderID	10489895
synonyms	DXO, Dextrorphanol
	C
H	23
N	1
O	1
SMILES	CN1CC[C@@]23CCCC[C@@H]2[C@@H]1Cc4c3cc(O)cc4
StdInChI_Ref
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
StdInChIKey	JAQUASYNZVUNQP-PVAVHDDUSA-N
::

| tradename = | legal_US = Unscheduled

| C = 17 | H = 23 | N = 1 | O = 1 | SMILES = CN1CC[C@@]23CCCC[C@@H]2[C@@H]1Cc4c3cc(O)cc4 | StdInChI_Ref = | 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 = | 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.

Pharmacology

Pharmacodynamics

::data[format=table title="Dextrorphan{{cite web | title = PDSP K_i 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
[NMDAR
(MK-801)](nmda-receptor)	486–906	Rat
σ1	118–481	Rat
σ2	11,325–15,582	Rat
	420
1,000	Rat
Human	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.
	34,700	Rat
	5,950	Rat
	401–484	Rat
	≥340	Rat
	1,000	Rat
5-HT1A	1,000	Rat
5-HT1B/1D	54% at 1 μM	Rat
5-HT2A	1,000	Rat
α1	1,000	Rat
α2	1,000	Rat
β	35% at 1 μM	Rat
D2	1,000	Rat
H1	95% at 1 μM	Rat
	100% at 1 μM	Rat
	1,300–29,600
(IC50)	Rat
	ND	ND	ND
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 (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. 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. It is further converted to 3-HM by CYP3A4 or glucuronidated.

Society and culture

Legal status

Dextrorphan was formerly a Schedule I controlled substance in the United States, but was unscheduled on October 1, 1976.

Research

Dextrorphan was under development for the treatment of stroke, and reached phase II clinical trials for this indication, but development was discontinued.

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.

References

Bensinger, Peter. (October 1, 1976). "Dextrophan and Nalbuphine; Removal from Schedules".
(August 1998). "Psychotropic effects of dextromethorphan are altered by the CYP2D6 polymorphism: a pilot study". Journal of Clinical Psychopharmacology.
"PDSP K_i Database". University of North Carolina at Chapel Hill and the United States National Institute of Mental Health.
(2016). "Dextromethorphan: An update on its utility for neurological and neuropsychiatric disorders". Pharmacol. Ther..
(2007). "A comparison of the binding profiles of dextromethorphan, memantine, fluoxetine and amitriptyline: treatment of involuntary emotional expression disorder". Exp. Neurol..
(2016). "Pharmacology of dextromethorphan: Relevance to dextromethorphan/quinidine (Nuedexta®) clinical use". Pharmacol. Ther..
(1995). "Characterization of the cloned human mu opioid receptor". J. Pharmacol. Exp. Ther..
(May 2004). "Comparison of the effects of dextromethorphan, dextrorphan, and levorphanol on the hypothalamo-pituitary-adrenal axis". The Journal of Pharmacology and Experimental Therapeutics.
(November 2001). "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?". Drug Metabolism and Disposition.
DEA. "Lists of: Scheduling Actions Controlled Substances Regulated Chemicals".
"Dextrorphan - AdisInsight".
(May 2021). "Using Estrogenic Activity and Nontargeted Chemical Analysis to Identify Contaminants in Sewage Sludge". Environmental Science & Technology.

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