The mu1, mu2, 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 mu1, mu2, delta and kappa, in comparison with that of morphine. The analgesic R-methadone had a 10-fold higher affinity for mu1 receptors than S-methadone (IC50 3.0 nM and 26.4 nM, respectively). At the mu2 receptor, the IC50 value of R-methadone was 6.9 nM and 88 nM for S-methadone, respectively. As expected, R-methadone had twice the affinity for mu1 and mu2 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 effect of racemic methadone. R-methadone has a receptor binding profile which resembles that of morphine.
Kristensen
K
K
Department of Pharmaceutics, Royal Danish School of Pharmacy, Copenhagen.
Christensen
C B
CB
Christrup
L L
LL
D000818:Animals; D001667:Binding, Competitive; D002417:Cattle; D008691:Methadone / Q000378:metabolism* / Q000494:pharmacology; D009020:Morphine / Q000378:metabolism* / Q000494:pharmacology; D011485:Protein Binding; D011957:Receptors, Opioid / Q000378:metabolism*; D017465:Receptors, Opioid, delta / Q000378:metabolism; D017473:Receptors, Opioid, kappa / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000378:metabolism; D015203:Reproducibility of Results; D013237:Stereoisomerism
D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D009020:Morphine; D008691:Methadone