Clocinnamox antagonism of opioid suppression of schedule-controlled responding in rhesus monkeys.
The antagonist effects of clocinnamox were evaluated against opioid agonists, acting at mu, kappa and delta-receptors, in rhesus monkeys (n = 3-4) responding under a fixed-ratio 30 (FR 30) schedule for food delivery. Clocinnamox (0.032-0.1 mg/kg) dose-dependently antagonized fentanyl (0.001-0.32 mg/kg) after either a 3-h or 1-day pretreatment; there was substantial recovery of agonist potency by 1 week after clocinnamox. Etonitazene (0.0001-0.01 mg/kg) was also antagonized by clocinnamox (0.1 mg/kg), but to a lesser extent than fentanyl. The smaller extent of antagonism was not due to the appearance of non mu-opioid response-decreasing effects of etonitazene, since the competitive antagonist quadazocine (0.1 mg/kg) shifted the etonitazene dose-effect 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 delta-agonist BW373U86 (0.0.01-1.0 mg/kg) or the kappa-agonist U69,593 (0.001-0.032 mg/kg). These results are consistent with previous in vivo and in vitro evidence that characterized clocinnamox as an insurmountable antagonist, with selectivity for mu- over kappa- and delta-receptors.
Butelman
E R
ER
Department of Pharmacology, University of Michigan, Ann Arbor 48109, USA.
Negus
S S
SS
Lewis
J W
JW
Woods
J H
JH
D000818:Animals; D002934:Cinnamates / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D008253:Macaca mulatta; D008297:Male; D009022:Morphine Derivatives / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000494:pharmacology*; D018847:Opioid Peptides / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D017465:Receptors, Opioid, delta / Q000819:agonists; D017450:Receptors, Opioid, mu / Q000819:agonists; D017480:Receptors, sigma / Q000819:agonists; D012055:Reinforcement Schedule
D002934:Cinnamates; D009022:Morphine Derivatives; D009292:Narcotic Antagonists; D018847:Opioid Peptides; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; D017480:Receptors, sigma; C076806:clocinnamox