Pharmacologic and reinforcing properties of phencyclidine and the enantiomers of N-allylnormetazocine in the dog.
Experiments were conducted to evaluate the degree of phencyclidine (PCP)-like activity associated with the dextro and levo enantiomers of the sigma agonist N-allylnormetazocine (NANM). In chronic spinal dogs, d- and l-NANM generally produced similar physiologic and gross animal behavior effects which included miosis, tachycardia, hyperthermia, increased secretory activity (lacrimation, rhinorrhea and salivation), nystagmus and stereotyped head movements. For these effects, d- and l-NANM were generally equal in potency and both were about 1/10th as potent as PCP. However, the NANM enantiomers could be differentiated on the basis of their effects on nociceptive reflexes. Comparisons of dose-response curves and efficacies demonstrated that d-NANM was more similar to PCP in its effectiveness in depressing the flexor and skin twitch reflexes than was l-NANM. In addition, naltrexone selectively antagonized or reduced only the effects of l-NANM on reflex activity. In intact dogs, d-NANM and PCP, but not l-NANM maintained self-administration behavior under FR15 or FI900 (FR10:S) schedules of reinforcement. This represented the most stereospecific action of the NANM enantiomers. Additionally, l-NANM failed to maintain self-administration behavior, even following pretreatment with naltrexone, thus suggesting that the opiate activity of l-NANM was not responsible for its lack of reinforcing efficacy. Taken together, the data demonstrate that both d- and l-NANM have PCP-like properties, but d-NANM is pharmacologically more equivalent than l-NANM to PCP and l-NANM has additional activity which is not PCP-like.
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003216:Conditioning, Operant / Q000187:drug effects*; D003655:Decerebrate State; D004285:Dogs; D005260:Female; D009020:Morphine / Q000494:pharmacology; D009271:Naltrexone / Q000494:pharmacology; D010620:Phenazocine / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D010622:Phencyclidine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D012055:Reinforcement Schedule; D012646:Self Administration; D013237:Stereoisomerism
D009271:Naltrexone; C012134:SK&F 10047; D009020:Morphine; D010620:Phenazocine; D010622:Phencyclidine