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

Rationale: Methoclocinnamox (MC-CAM) possesses initial partial μ-opioid agonist activity with subsequent long-lasting μ-antagonist effects. This profile of activity is similar to that of buprenorphine, a compound with proposed use in the treatment of opioid abuse, suggesting a possible therapeutic use for MC-CAM as well. Objective: The current study assessed the time course of the ability of MC-CAM and buprenorphine to antagonize the reinforcing effects of alfentanil and compared this with that of buprenorphine. Methods: Rhesus monkeys self-administered a range of doses of alfentanil (0.03-1 μg/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 which alfentanil was available. In the pretreatment studies, a wider range of alfentanil doses was utilized (0.03-30 μg/kg 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 prior to a session in which alfentanil was available, produced a decrease in the reinforcing potency of alfentanil. The antagonist effects of the pretreatments were largest 30 min following administration and decreased over the next several days. The duration of MC-CAM's antagonism of alfentanil was approximately 4 days; the duration of buprenorphine as an antagonist was approximately 2 days. Conclusion: These data suggest that MC-CAM has a longer duration of antagonist effects than buprenorphine and it may therefore have an advantage in the treatment of opioid abuse.