THE MU(1), MU(2), DELTA, KAPPA-OPIOID RECEPTOR-BINDING PROFILES OF METHADONE STEREOISOMERS AND MORPHINE

The binding affinities of racemic methadone and its optical isomers R- methadone and S-methadone were evaluated for the opioid receptors mu(1 ), mu(2), delta and kappa, in comparison with that of morphine. The an algesic R-methadone had a 10-fold higher affinity for mu(1) receptors than S-methadone (IC50 3.0 nM and 26.4 nM, respectively). At the mu(2) receptor, the IC50 value of R-methadone was 6.9 nM and 88 nM for S-me thadone, respectively As expected, R-methadone had twice the affinity for mu(1) and mu(2) receptors than the racemate. All of the compounds tested had low affinity for the delta and kappa receptors. This result suggests that S-methadone does not essentially contribute to opioid e ffect of racemic methadone. R-methadone has a receptor binding profile which resembles that of morphine.