Dextrorphan Explained
| Verifiedfields: | changed |
| Watchedfields: | changed |
| Verifiedrevid: | 408496712 |
| Iupac Name: | (+)-17-methyl-9a,13a,14a-morphinan-3-ol |
| Legal Us: | Unscheduled[1] |
| Cas Number: | 125-73-5 |
| Atc Prefix: | None |
| Pubchem: | 5360697 |
| Unii: | 04B7QNO9WS |
| Chembl: | 1254766 |
| 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: | 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: | 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.[2]
Pharmacology
Pharmacodynamics
Dextrorphan[3] [4] [5] [6] | Site | Ki (nM) | Species | Ref |
|---|
| 486–906 | Rat | |
| 118–481 | Rat | |
| 11,325–15,582 | Rat | |
| 420
>1,000 | Rat
Human | [7] |
| 34,700 | Rat | |
| 5,950 | Rat | |
| 401–484 | Rat | |
| ≥340 | Rat | |
| >1,000 | Rat | |
| >1,000 | Rat | |
| 54% at 1 μM | Rat | |
| >1,000 | Rat | |
| >1,000 | Rat | |
| >1,000 | Rat | |
| 35% at 1 μM | Rat | |
| >1,000 | Rat | |
| 95% at 1 μM | Rat | |
| 100% at 1 μM | Rat | |
| 1,300–29,600
(IC50) | Rat | |
| | | |
| 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 as well much less active as a serotonin reuptake inhibitor, but retains DXM's activity as a norepinephrine reuptake inhibitor.[8] 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.[9]
Society and culture
Legal status
Dextrorphan was formerly a Schedule I controlled substance in the United States, but was unscheduled on October 1, 1976.[10]
Research
Dextrorphan was under development for the treatment of stroke, and reached phase II clinical trials for this indication, but development was discontinued.[11]
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.[12]
See also
Notes and References
- Web site: Bensinger . Peter . October 1, 1976 . Dextrophan and Nalbuphine; Removal from Schedules . June 26, 2023 . NARA.
- Zawertailo LA, Kaplan HL, Busto UE, Tyndale RF, Sellers EM . Psychotropic effects of dextromethorphan are altered by the CYP2D6 polymorphism: a pilot study . Journal of Clinical Psychopharmacology . 18 . 4 . 332–337 . August 1998 . 9690700 . 10.1097/00004714-199808000-00014 .
- Web site: PDSP Ki Database . Psychoactive Drug Screening Program (PDSP). Bryan Roth. Roth BL, Driscol J . University of North Carolina at Chapel Hill and the United States National Institute of Mental Health . 14 August 2017 .
- Nguyen L, Thomas KL, Lucke-Wold BP, Cavendish JZ, Crowe MS, Matsumoto RR . Dextromethorphan: An update on its utility for neurological and neuropsychiatric disorders . Pharmacol. Ther. . 159 . 1–22 . 2016 . 26826604 . 10.1016/j.pharmthera.2016.01.016 .
- Werling LL, Keller A, Frank JG, Nuwayhid SJ . A comparison of the binding profiles of dextromethorphan, memantine, fluoxetine and amitriptyline: treatment of involuntary emotional expression disorder . Exp. Neurol. . 207 . 2 . 248–57 . 2007 . 17689532 . 10.1016/j.expneurol.2007.06.013 . 38476281 .
- Taylor CP, Traynelis SF, Siffert J, Pope LE, Matsumoto RR . Pharmacology of dextromethorphan: Relevance to dextromethorphan/quinidine (Nuedexta®) clinical use . Pharmacol. Ther. . 164 . 170–82 . 2016 . 27139517 . 10.1016/j.pharmthera.2016.04.010 . free .
- Raynor K, Kong H, Mestek A, Bye LS, Tian M, Liu J, Yu L, Reisine T . Characterization of the cloned human mu opioid receptor . J. Pharmacol. Exp. Ther. . 272 . 1 . 423–8 . 1995 . 7815359 .
- Pechnick RN, Poland RE . Comparison of the effects of dextromethorphan, dextrorphan, and levorphanol on the hypothalamo-pituitary-adrenal axis . The Journal of Pharmacology and Experimental Therapeutics . 309 . 2 . 515–522 . May 2004 . 14742749 . 10.1124/jpet.103.060038 . 274504 .
- Yu A, Haining RL . 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 . 29 . 11 . 1514–20 . November 2001 . 11602530 .
- Web site: Lists of: Scheduling Actions Controlled Substances Regulated Chemicals . DEA . 2010-09-24 . 2016-04-17 . https://web.archive.org/web/20160417085648/http://www.deadiversion.usdoj.gov/schedules/orangebook/orangebook.pdf . dead .
- Web site: Dextrorphan - AdisInsight.
- Black GP, He G, Denison MS, Young TM . Using Estrogenic Activity and Nontargeted Chemical Analysis to Identify Contaminants in Sewage Sludge . Environmental Science & Technology . 55 . 10 . 6729–6739 . May 2021 . 33909413 . 8378343 . 10.1021/acs.est.0c07846 . 2021EnST...55.6729B .
