Abstract
The antagonist effects of clocinnamox were evaluated against opioid agonists, acting at μ, κ and ∂-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 μ-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 ∂-agonist BW373U86 (0.0.01-1.0 mg/kg) or the κ-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 μ-over κ- and δ-receptors.
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Animals used in these studies were maintained in accordance with the University Committees on the Use and Care of Animals, University of Michigan, and Guidelines of the Committee on the Care and Use of Laboratory Animals of the Institute of Laboratory Animal Resources, National Health Council (Department of Health, Education and Welfare, Publication No. (NIH) 85-23, revised 1983). Support for this research was provided by USPHS grant DA 00254.
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Butelman, E.R., Negus, S.S., Woods, J.H. et al. Clocinnamox antagonism of opioid suppression of schedule-controlled responding in rhesus monkeys. Psychopharmacology 123, 320–324 (1996). https://doi.org/10.1007/BF02246641
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DOI: https://doi.org/10.1007/BF02246641