Esmethadone

Esmethadone
Clinical data
Other namesDextromethadone; d-Methadone; S-Methadone; (+)-Methadone
Identifiers
  • (6S)-6-(Dimethylamino)-4,4-diphenylheptan-3-one
CAS Number
PubChem CID
ChemSpider
UNII
ChEBI
CompTox Dashboard (EPA)
ECHA InfoCard100.164.915 Edit this at Wikidata
Chemical and physical data
FormulaC21H27NO
Molar mass309.453 g·mol−1
3D model (JSmol)
  • CCC(=O)C(C[C@H](C)N(C)C)(C1=CC=CC=C1)C2=CC=CC=C2
  • InChI=1S/C21H27NO/c1-5-20(23)21(16-17(2)22(3)4,18-12-8-6-9-13-18)19-14-10-7-11-15-19/h6-15,17H,5,16H2,1-4H3/t17-/m0/s1
  • Key:USSIQXCVUWKGNF-KRWDZBQOSA-N

Esmethadone (INNTooltip International Nonproprietary Name; developmental code name REL-1017), also known as dextromethadone, is the (S)-enantiomer of methadone. It acts as an N-methyl-D-aspartate receptor (NMDAR) antagonist, among other actions. Unlike levomethadone, it has low affinity for opioid receptors and lacks significant respiratory depressant action and abuse liability.

Esmethadone has been under development for major depressive disorder.

There is an asymmetric synthesis available to prepare both esmethadone (S-(+)-methadone) and levomethadone (R-(−)-methadone).

Receptor binding affinities of isomers of methadone
Compound Affinities (KiTooltip Inhibitor constant, in nM) Ratios
MORTooltip μ-Opioid receptor DORTooltip δ-Opioid receptor KORTooltip κ-opioid receptor SERTTooltip Serotonin transporter NETTooltip Norepinephrine transporter NMDARTooltip N-Methyl-D-aspartate receptor M:D:K SERT:NET
Racemic methadone 1.74354051,4002592,500–8,3001:256:2381:5
Dextromethadone 19.79601,37099212,7002,600–7,4001:49:701:13
Levomethadone 0.9453711,86014.17022,800–3,4001:393:19681:50

References

  1. 1 2 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.
  2. ↑ "METHADONE" (PDF). Drug & Chemical Evaluation Section. Drug Enforcement Agency. Retrieved 14 November 2020.
  3. 1 2 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.
  4. ↑ "Dextromethadone - Cornell University/Relmada Therapeutics - AdisInsight".
  5. ↑ 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.
  6. ↑ US patent 6143933