Abstract
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 para digm. 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.
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Received: 27 April 1999 / Final version: 29 September 1999
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Briscoe, R., Winger, G., Lewis, J. et al. Methoclocinnamox: time course of changes in alfentanil-reinforced responding in rhesus monkeys. Psychopharmacology 148, 393–399 (2000). https://doi.org/10.1007/s002130050068
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DOI: https://doi.org/10.1007/s002130050068