AGONIST PROPERTIES OF METHADONE AT THE CLONED RAT MU-OPIOID RECEPTOR

We have studied how methadone, a potent opiate analgesic commonly used in the treatment of heroin addiction, inhibits cAMP accumulation by i ts interaction with the recently cloned rat mu opioid receptor. We hav e measured cAMP levels in Chinese hamster ovary (CHO) cells that stabl y expressed the mu receptor cDNA. When these cells were stimulated wit h 10 mu M forskolin, methadone was able to inhibit the accumulation of cAMP with an IC50 of 28.3 nM. Moreover, methadone's inhibition of cAM P production was reversible by naloxone and was pertussis toxin sensit ive. These findings are consistent with the interpretation that methad one binding to the mu opioid receptor is coupled to the activation of a Gi/Go protein.