Dextrorphan

Source: Wikipedia, the free encyclopedia.
Not to be confused with Dextromethorphan or Dextrallorphan.
Dextrorphan
Clinical data
Other namesDXO, Dextrorphanol
ATC code
  • None
Legal status
Legal status
  • US: Unscheduled[1]
Identifiers
  • (+)-17-methyl-9a,13a,14a-morphinan-3-ol
JSmol)
  • CN1CC[C@@]23CCCC[C@@H]2[C@@H]1Cc4c3cc(O)cc4
  • InChI=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 ☒N
  • Key:JAQUASYNZVUNQP-PVAVHDDUSA-N ☒N
 ☒NcheckY (what is this?)  (verify)

Dextrorphan (DXO) is a

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
NMDAR
(MK-801)		 486–906 Rat [4]
σ1 118–481 Rat [4]
σ2 11,325–15,582 Rat [4]
MOR
Tooltip μ-Opioid receptor		 420
>1,000		 Rat
Human		 [4][7]
DOR
Tooltip δ-Opioid receptor		 34,700 Rat [4]
KOR
Tooltip 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]
mAChRs
Tooltip Muscarinic acetylcholine receptors		 100% at 1 μM Rat [4]
nAChRs
Tooltip Nicotinic acetylcholine receptors		 1,300–29,600
(IC50)		 Rat [4]
VDSCs
Tooltip 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 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.[citation needed] 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

estrogenic activity by using predictive modelling, before observing it in in vitro. [12]

See also

References

  1. NARA
    . Retrieved June 26, 2023.
  2. PMID 9690700
    .
  3. ^ Roth BL, Driscol J. "PDSP Ki Database". Psychoactive Drug Screening Program (PDSP). University of North Carolina at Chapel Hill and the United States National Institute of Mental Health. Retrieved 14 August 2017.
  4. ^
    PMID 26826604
    .
  5. S2CID 38476281
    .
  6. PMID 27139517
    .
  7. PMID 7815359
    .
  8. S2CID 274504
    .
  9. PMID 11602530
    .
  10. ^ DEA. "Lists of: Scheduling Actions Controlled Substances Regulated Chemicals" (PDF). Archived from the original (PDF) on 2016-04-17. Retrieved 2010-09-24.
  11. ^ "Dextrorphan - AdisInsight".
  12. PMID 33909413
    .