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


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 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).


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.


CONCLUSIONS
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.
Briscoe
R J
RJ
Department of Pharmacology, University of Michigan, Ann Arbor, 48109-0632, USA.
Winger
G
G
Lewis
J W
JW
Woods
J H
JH
D015760:Alfentanil / Q000008:administration & dosage / Q000494:pharmacology*; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D002934:Cinnamates / Q000008:administration & dosage / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects; D005260:Female; D007262:Infusions, Intravenous; D008253:Macaca mulatta; D008297:Male; D009022:Morphine Derivatives / Q000008:administration & dosage / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D017450:Receptors, Opioid, mu / Q000819:agonists* / Q000037:antagonists & inhibitors; D012055:Reinforcement Schedule; D013997:Time Factors
D000701:Analgesics, Opioid; D002934:Cinnamates; D009022:Morphine Derivatives; D009292:Narcotic Antagonists; D017450:Receptors, Opioid, mu; C076806:clocinnamox; D015760:Alfentanil