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| Other names | DXO, Dextrorphanol |
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| ECHA InfoCard | 100.004.323 |
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| Formula | C17H23NO |
| Molar mass | 257.377 g·mol−1 |
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Dextrorphan (DXO) is apsychoactive drug of themorphinan class which acts as anantitussive orcough suppressant and in high doses adissociativehallucinogen. It is thedextrorotatoryenantiomer ofracemorphan; thelevorotatory enantiomer islevorphanol. Dextrorphan is produced by O-demethylation ofdextromethorphan byCYP2D6. Dextrorphan is anNMDA antagonist and contributes to the psychoactive effects of dextromethorphan.[2]
| Site | Ki (nM) | Species | Ref |
|---|---|---|---|
| NMDAR (MK-801) | 486–906 | Rat | [4] |
| σ1 | 118–481 | Rat | [4] |
| σ2 | 11,325–15,582 | Rat | [4] |
| MORTooltip μ-Opioid receptor | 420 >1,000 | Rat Human | [4][7] |
| DORTooltip δ-Opioid receptor | 34,700 | Rat | [4] |
| KORTooltip κ-Opioid receptor | 5,950 | Rat | [4] |
| SERTTooltip Serotonin transporter | 401–484 | Rat | [4] |
| NETTooltip Norepinephrine transporter | ≥340 | Rat | [4] |
| DATTooltip Dopamine transporter | >1,000 | Rat | [4] |
| 5-HT1A | >1,000 | Rat | [4] |
| 5-HT1B/1D | 54% at 1 μM | Rat | [4] |
| 5-HT2A | >1,000 | Rat | [4] |
| α1 | >1,000 | Rat | [4] |
| α2 | >1,000 | Rat | [4] |
| β | 35% at 1 μM | Rat | [4] |
| D2 | >1,000 | Rat | [4] |
| H1 | 95% at 1 μM | Rat | [4] |
| mAChRsTooltip Muscarinic acetylcholine receptors | 100% at 1 μM | Rat | [4] |
| nAChRsTooltip Nicotinic acetylcholine receptors | 1,300–29,600 (IC50) | Rat | [4] |
| VDSCsTooltip Voltage-dependent sodium channels | 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 ofdextromethorphan (DXM). However, dextrorphan is much more potent as an NMDA receptor antagonist and much less active as aserotonin reuptake inhibitor, but retains DXM's activity as anorepinephrine reuptake inhibitor.[8]It also has more affinity for the opioid receptors than dextromethorphan, significantly so at high doses.
Dextrorphan has a notably longerelimination 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] It is further converted to3-HM byCYP3A4 orglucuronidated.[9]
Dextrorphan was formerly aSchedule Icontrolled substance in theUnited States, but was unscheduled on October 1, 1976.[10]
Dextrorphan was under development for the treatment ofstroke, and reachedphase IIclinical trials for this indication, but development was discontinued.[11]
In 2021, dextrorphan was identified in >75% of sludge samples taken from 12wastewater treatment plants inCalifornia. The same study associated dextrorphan withestrogenic activity by usingpredictive modelling, before observing it inin vitro.[12]