title: Discriminative effects of ethylketazocine in the rat: stereospecificity and antagonism by naloxone.
abstract: Male F344 rats were trained to discriminate between saline and d,l-ethylketazocine (EKC) in a two-choice discrete-trial avoidance task and tested with the l- and d-isomers of EKC, cyclazocine, and SKF-10,047. The effectiveness of naloxone in antagonizing the discriminative effects of d,l-EKC was also determined. Each of the l-isomers tested produced dose-related stimulus control of behavior similar to that produced by d,l-EKC. l-EKC was the most potent isomer tested, being approximately twice as potent as d,l-EKC. In contrast, d-EKC was completely devoid of activity at 300-fold higher doses. l-Cyclazocine and l-SKF-10,047 were approximately 4- and 30-fold less potent, respectively, than d,l-EKC. Although both d-cyclazocine and d-SKF-10,047 produced some drug-appropriate responding, both compounds were less potent and less efficacious than their respective l-isomers and both were significantly less efficacious than d,l-EKC. Increasing doses of naloxone (0.1 - 1.0 mg/kg) produced parallel shifts to the right in the d,l-EKC dose-effect curve. These results suggest that the discriminative effects of EKC are mediated by a stereospecific naloxone-sensitive receptor.
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects*; D003496:Cyclazocine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004192:Discrimination, Psychological / Q000187:drug effects*; D004336:Drug Antagonism; D016314:Ethylketocyclazocine; D008297:Male; D009270:Naloxone / Q000494:pharmacology*; D010620:Phenazocine / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D000701:Analgesics, Opioid; D009270:Naloxone; D016314:Ethylketocyclazocine; C012134:SK&F 10047; D010620:Phenazocine; D003496:Cyclazocine