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 its interaction with the recently cloned rat mu opioid receptor. We have measured cAMP levels in Chinese hamster ovary (CHO) cells that stably expressed the mu receptor cDNA. When these cells were stimulated with 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 cAMP production was reversible by naloxone and was pertussis toxin sensitive. These findings are consistent with the interpretation that methadone binding to the mu opioid receptor is coupled to the activation of a Gi/Go protein.