Methoclocinnamox: time course of changes in alfentanil-reinforced responding in rhesus monkeys

Rationale: Methoclocinnamox (MC-CAM) possesses initial partial mu-opioid ag onist activity with subsequent long-lasting mu-antagonist effects. This pro file of activity is similar to that of buprenorphine, a compound with propo sed use in the treatment of opioid abuse, suggesting a possible therapeutic use for MC-CAM as well. Objective: The current study assessed the time cou rse of the ability of MC-CAM and buprenorphine to antagonize the reinforcin g effects of alfentanil and compared this with that of buprenorphine, Metho ds: Rhesus monkeys self-administered a range of doses of alfentanil (0.03-1 mu g/kg per injection) under a fixed-ratio 30, time-out 45 s schedule of i .v. drug delivery. MC-CAM was substituted for alfentanil on occasion, and a dose of 1.0 mg/kg MC-CAM or buprenorphine was given prior to sessions in w hich alfentanil was available. In the pretreatment studies, a wider range o f alfentanil doses was utilized (0.03-30 mu g/g per injection). Results: MC -CAM maintained self-administration behavior and was nearly equipotent with buprenorphine as a reinforcer in this paradigm. Both drugs, when given pri or to a session in which alfentanil was available, produced a decrease in t he reinforcing potency of alfentanil, The antagonist effects of the pretrea tments were largest 30 min following administration and decreased over the next several days. The duration of MC-CAM's antagonism of alfentanil was ap proximately 4 days; the duration of buprenorphine as an antagonist was appr oximately 2 days. Conclusion: These data suggest that MC-CAM has a longer d uration of antagonist effects than buprenorphine and it may therefore have an advantage in the treatment of opioid abuse.