CLOCINNAMOX ANTAGONISM OF OPIOID SUPPRESSION OF SCHEDULE-CONTROLLED RESPONDING IN RHESUS-MONKEYS

The antagonist effects of clocinnamox were evaluated against opioid ag onists, acting at mu, kappa and partial derivative-receptors, in rhesu s monkeys (n=3-4) responding under a fixed-ratio 30 (FR 30) schedule f or food delivery. Clocinnamox (0.032-0.1 mg/kg) dose-dependently antag onized fentanyl (0.001-0.32 mg/kg) after either a 3-h or 1-day pretrea tment; there was substantial recovery of agonist potency by 1 week aft er clocinnamox. Etonitazene (0.0001-0.01 mg/kg) was also antagonized b y clocinnamox (0.1 mg/kg), but to a lesser extent than fentanyl. The s maller extent of antagonism was not due to the appearance of non mu-op ioid response-decreasing effects of etonitazene, since the competitive antagonist quadazocine (0.1 mg/kg) shifted the etonitazene dose-effec t curve in the presence of clocinnamox (0.1 mg/kg). Clocinnamox (0.1-0 .32 mg/kg) did not antagonize the rate-suppressing effects of the part ial derivative-agonist BW373U86 (0.0.01-1.0 mg/kg) or the kappa-agonis t U69,593 (0.001-0.032 mg/kg). These results are consistent with previ ous in vivo and in vitro evidence that characterized clocinnamox as an insurmountable antagonist, with selectivity for mu- over kappa- and d elta-receptors.