• R J Briscoe, G Winger, J W Lewis, and J H Woods.
• Department of Pharmacology, University of Michigan, Ann Arbor, 48109-0632, USA.
• Psychopharmacology (Berl.). 2000 Mar 1;148(4):393-9.

RationaleMethoclocinnamox (MC-CAM) possesses initial partial micro-opioid agonist activity with subsequent long-lasting micro-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.ObjectiveThe 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.MethodsRhesus monkeys self-administered a range of doses of alfentanil (0.03-1 microg/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 microg/kg per injection).ResultsMC-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.ConclusionThese 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.

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