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).

vte Receptor binding affinities of isomers of methadone
CompoundAffinities (KiTooltip Inhibitor constant, in nM)Ratios
MORTooltip μ-Opioid receptorDORTooltip δ-Opioid receptorKORTooltip κ-Opioid receptorSERTTooltip Serotonin transporterNETTooltip Norepinephrine transporterNMDARTooltip N-Methyl-D-aspartate receptorM:D:KSERT:NET
Racemic methadone1.74354051,4002592,500–8,3001:256:2381:5
Dextromethadone19.79601,37099212,7002,600–7,4001:49:701:13
Levomethadone0.9453711,86014.17022,800–3,4001:393:19681:50