Dextromethadone
Dextromethadone (developmental code name REL-1017) is the (S)-enantiomer of methadone.[1] It acts as an N-methyl-D-aspartate receptor (NMDAR) antagonist.[2] The compound also has low affinity for opioid receptors,[3] however, according to a DEA publication, the d-isomer "lacks significant respiratory depressant action and abuse liability."[4] Dextromethadone is under development for the treatment of Major depressive disorder (MDD). There is an asymmetric synthesis available to prepare both dextromethadone (S-(+)-methadone) and levomethadone (R-(−)-methadone).[5][6]
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| Other names | d-Methadone; 6S-Methadone; (+)-Methadone |
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| ECHA InfoCard | 100.164.915  |
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| Formula | C21H27NO |
| Molar mass | 309.453 g·mol−1 |
| 3D model (JSmol) | |
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| Compound | Affinities (Ki, in nM) | Ratios | ||||||
|---|---|---|---|---|---|---|---|---|
| MOR | DOR | KOR | SERT | NET | NMDAR | M:D:K | SERT:NET | |
| Racemic methadone | 1.7 | 435 | 405 | ND | ND | 2,500–8,300 | 1:256:238 | ND |
| Dextromethadone | 19.7 | 960 | 1,370 | 992 | 12,700 | 2,600–7,400 | 1:49:70 | 1:13 |
| Levomethadone | 0.945 | 371 | 1,860 | 14.1 | 702 | 2,800–3,400 | 1:393:1968 | 1:50 |
References
- https://adisinsight.springer.com/drugs/800038927
- Gorman AL, Elliott KJ, Inturrisi CE (February 1997). "The d- and l-isomers of methadone bind to the non-competitive site on the N-methyl-D-aspartate (NMDA) receptor in rat forebrain and spinal cord". Neurosci. Lett. 223 (1): 5–8. doi:10.1016/S0304-3940(97)13391-2. PMID 9058409.
- "METHADONE" (PDF). Drug & Chemical Evaluation Section. Drug Enforcement Agency. Retrieved 14 November 2020.
- Codd EE, Shank RP, Schupsky JJ, Raffa RB (1995). "Serotonin and norepinephrine uptake inhibiting activity of centrally acting analgesics: structural determinants and role in antinociception". J. Pharmacol. Exp. Ther. 274 (3): 1263–70. PMID 7562497.
- Hull JD, Scheinmann F, Turner NJ (March 2003). "Synthesis of optically active methadones, LAAM and bufuralol by lipase-catalysed acylations". Tetrahedron: Asymmetry. 14 (5): 567–576. doi:10.1016/S0957-4166(03)00019-3.
- US patent 6143933
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