Dextrorphan

Dextrorphan
Clinical data
Other names	DXO
ATC code	None;
Legal status
Legal status	US: Unscheduled ;
Identifiers
	IUPAC name (+)-17-methyl-9a,13a,14a-morphinan-3-ol;
CAS Number	125-73-5 ;
PubChem CID	5360697;
ChemSpider	10489895 ;
UNII	04B7QNO9WS;
ChEMBL	ChEMBL341216 ;
CompTox Dashboard (EPA)	DTXSID301014178 ;
ECHA InfoCard	100.004.323
Chemical and physical data
Formula	C17H23NO
Molar mass	257.377 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES CN1CC[[email protected]@]23CCCC[[email protected]@H]2[[email protected]@H]1Cc4c3cc(O)cc4;
	InChI 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 ; Key:JAQUASYNZVUNQP-PVAVHDDUSA-N ;
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Dextrorphan (DXO) is a psychoactive drug of the morphinan class which acts as an antitussive or cough suppressant and dissociative hallucinogen. It is the dextrorotatory-stereoisomer of racemorphan, the levo-half being levorphanol. Dextrorphan is produced by O-demethylation of dextromethorphan by CYP2D6. Dextrorphan is an NMDA antagonist and contributes to the psychoactive effects of dextromethorphan.^[1]

Pharmacology

Pharmacodynamics

Dextrorphan^[2]^[3]^[4]^[5]
Site	K_i (nM)	Species	Ref
NMDAR (MK-801)	486–906	Rat	^[3]
σ₁	118–481	Rat	^[3]
σ₂	11,325–15,582	Rat	^[3]
MOR	420 >1,000	Rat Human	^[3]^[6]
DOR	34,700	Rat	^[3]
KOR	5,950	Rat	^[3]
SERT	401–484	Rat	^[3]
NET	≥340	Rat	^[3]
DAT	>1,000	Rat	^[3]
5-HT_1A	>1,000	Rat	^[3]
5-HT_1B_/_1D	54% at 1 μM	Rat	^[3]
5-HT_2A	>1,000	Rat	^[3]
α₁	>1,000	Rat	^[3]
α₂	>1,000	Rat	^[3]
β	35% at 1 μM	Rat	^[3]
D₂	>1,000	Rat	^[3]
H₁	95% at 1 μM	Rat	^[3]
mAChRs	100% at 1 μM	Rat	^[3]
nAChRs	1,300–29,600 (IC₅₀)	Rat	^[3]
VDSCs	ND	ND	ND
Values are K_i (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.^[7]

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]}

Society and culture

Legal status

Dextrorphan was formerly a Schedule I controlled substance in the United States, but was unscheduled on October 1, 1976.^[8]

Research

Dextrorphan was under development for the treatment of stroke, and reached phase II clinical trials for this indication, but development was discontinued.^[9]

References

^ Zawertailo, L. A.; Kaplan, H. L.; Busto, U. E.; Tyndale, R. F.; Sellers, E. M. (Aug 1998). "Psychotropic Effects of Dextromethorphan are Altered by the CYP2D6 Polymorphism: A Pilot Study". Journal of Clinical Psychopharmacology. 18 (4): 332–337. doi:10.1097/00004714-199808000-00014. PMID 9690700.
^ Roth, BL; Driscol, J. "PDSP K_i 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.
^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j ^k ^l ^m ⁿ ^o ^p ^q ^r ^s ^t Nguyen L, Thomas KL, Lucke-Wold BP, Cavendish JZ, Crowe MS, Matsumoto RR (2016). "Dextromethorphan: An update on its utility for neurological and neuropsychiatric disorders". Pharmacol. Ther. 159: 1–22. doi:10.1016/j.pharmthera.2016.01.016. PMID 26826604.
^ Werling LL, Keller A, Frank JG, Nuwayhid SJ (2007). "A comparison of the binding profiles of dextromethorphan, memantine, fluoxetine and amitriptyline: treatment of involuntary emotional expression disorder". Exp. Neurol. 207 (2): 248–57. doi:10.1016/j.expneurol.2007.06.013. PMID 17689532. S2CID 38476281.
^ Taylor CP, Traynelis SF, Siffert J, Pope LE, Matsumoto RR (2016). "Pharmacology of dextromethorphan: Relevance to dextromethorphan/quinidine (Nuedexta®) clinical use". Pharmacol. Ther. 164: 170–82. doi:10.1016/j.pharmthera.2016.04.010. PMID 27139517.
^ Raynor K, Kong H, Mestek A, Bye LS, Tian M, Liu J, Yu L, Reisine T (1995). "Characterization of the cloned human mu opioid receptor". J. Pharmacol. Exp. Ther. 272 (1): 423–8. PMID 7815359.
^ Pechnick, R. N.; Poland, R. E. (2004). "Comparison of the Effects of Dextromethorphan, Dextrorphan, and Levorphanol on the Hypothalamo-Pituitary-Adrenal Axis". Journal of Pharmacology and Experimental Therapeutics. 309 (2): 515–522. doi:10.1124/jpet.103.060038. PMID 14742749. S2CID 274504.
^ DEA. "Lists of: Scheduling Actions Controlled Substances Regulated Chemicals" (PDF). Retrieved 2010-09-24.
^ [adisinsight.springer.com]

[1] Zawertailo, L. A.; Kaplan, H. L.; Busto, U. E.; Tyndale, R. F.; Sellers, E. M. (Aug 1998). "Psychotropic Effects of Dextromethorphan are Altered by the CYP2D6 Polymorphism: A Pilot Study". Journal of Clinical Psychopharmacology. 18 (4): 332–337. doi:10.1097/00004714-199808000-00014. PMID 9690700.

[PDSP-2] Roth, BL; Driscol, J. "PDSP K_i 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.

[pmid26826604-3] ^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j ^k ^l ^m ⁿ ^o ^p ^q ^r ^s ^t Nguyen L, Thomas KL, Lucke-Wold BP, Cavendish JZ, Crowe MS, Matsumoto RR (2016). "Dextromethorphan: An update on its utility for neurological and neuropsychiatric disorders". Pharmacol. Ther. 159: 1–22. doi:10.1016/j.pharmthera.2016.01.016. PMID 26826604.

[pmid17689532-4] Werling LL, Keller A, Frank JG, Nuwayhid SJ (2007). "A comparison of the binding profiles of dextromethorphan, memantine, fluoxetine and amitriptyline: treatment of involuntary emotional expression disorder". Exp. Neurol. 207 (2): 248–57. doi:10.1016/j.expneurol.2007.06.013. PMID 17689532. S2CID 38476281.

[pmid27139517-5] Taylor CP, Traynelis SF, Siffert J, Pope LE, Matsumoto RR (2016). "Pharmacology of dextromethorphan: Relevance to dextromethorphan/quinidine (Nuedexta®) clinical use". Pharmacol. Ther. 164: 170–82. doi:10.1016/j.pharmthera.2016.04.010. PMID 27139517.

[pmid7815359-6] Raynor K, Kong H, Mestek A, Bye LS, Tian M, Liu J, Yu L, Reisine T (1995). "Characterization of the cloned human mu opioid receptor". J. Pharmacol. Exp. Ther. 272 (1): 423–8. PMID 7815359.

[7] Pechnick, R. N.; Poland, R. E. (2004). "Comparison of the Effects of Dextromethorphan, Dextrorphan, and Levorphanol on the Hypothalamo-Pituitary-Adrenal Axis". Journal of Pharmacology and Experimental Therapeutics. 309 (2): 515–522. doi:10.1124/jpet.103.060038. PMID 14742749. S2CID 274504.

[urlDextrorphan_Legality-8] DEA. "Lists of: Scheduling Actions Controlled Substances Regulated Chemicals" (PDF). Retrieved 2010-09-24.

[AdisInsight-9] [adisinsight.springer.com]

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Clinical data


Other names	DXO
ATC code	None
Legal status
Legal status	US: Unscheduled
Identifiers
IUPAC name (+)-17-methyl-9a,13a,14a-morphinan-3-ol
CAS Number	125-73-5^Y
PubChem CID	5360697
ChemSpider	10489895^N
UNII	04B7QNO9WS
ChEMBL	ChEMBL341216^N
CompTox Dashboard (EPA)	DTXSID301014178
ECHA InfoCard	100.004.323
Chemical and physical data
Formula	C₁₇H₂₃NO
Molar mass	257.377 g·mol⁻¹
3D model (JSmol)	Interactive image
SMILES CN1CC[[email protected]@]23CCCC[[email protected]@H]2[[email protected]@H]1Cc4c3cc(O)cc4
InChI 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
^NY (what is this?) (verify)