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Dextromethadone

Dextromethadone
Dextromethadone.svg
Clinical data
Other namesd-Methadone; 6S-Methadone; (+)-Methadone
Identifiers
CAS Number
PubChem CID
ChemSpider
UNII
ECHA InfoCard100.164.915 Edit this at Wikidata
Chemical and physical data
FormulaC21H27NO
Molar mass309.453 g·mol−1
3D model (JSmol)

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 affinity for opioid receptors.[3] As of October 2019, dextromethadone is under development for the treatment of major depressive disorder.[1]

There is now an asymmetric synthesis[4] available to prepare both dextromethadone (S-(+)-methadone) and levomethadone (R-(−)-methadone).[5]

Methadone at opioid receptors, monoamine transporters, and the NMDA receptor

Compound Affinities (Ki) Ratios
MOR DOR KOR SERT NET NMDAR MOR:DOR:KOR SERT:NET
Methadone 1.7 nM 435 nM 405 nM ND ND 2,500–8,300 nM 1:256:238 ND
  Dextromethadone 19.7 nM 960 nM 1,370 nM 992 nM 12,700 nM 2,600–7,400 nM 1:49:70 1:13
  Levomethadone 0.945 nM 371 nM 1,860 nM 14.1 nM 702 nM 2,800–3,400 nM 1:393:1968 1:50
Sources: See template.

References

  1. ^ a b [adisinsight.springer.com]
  2. ^ Gorman AL, Elliott KJ, Inturrisi CE (14 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". Neuroscience Letters. 223 (1): 5–8. doi:10.1016/S0304-3940(97)13391-2. PMID 9058409.CS1 maint: uses authors parameter (link)
  3. ^ Codd EE, Shank RP, Schupsky JJ, Raffa RB (September 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.
  4. ^ 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.
  5. ^ US patent 6143933