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

Dextromethadone

Clinical data
Other names	d-Methadone; 6S-Methadone; (+)-Methadone
Identifiers
IUPAC name (6S)-6-(Dimethylamino)-4,4-diphenylheptan-3-one
CAS Number	5653-80-5
PubChem CID	643985
ChemSpider	559067
UNII	S95RZH8AMH
ECHA InfoCard	100.164.915
Chemical and physical data
Formula	C21H27NO
Molar mass	309.453 g·mol^−1
3D model (JSmol)	Interactive image
SMILES CCC(=O)C(C[C@H](C)N(C)C)(C1=CC=CC=C1)C2=CC=CC=C2
InChI 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

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. https://adisinsight.springer.com/drugs/800038927
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