Comparison of the pharmacologic effects of N-allylnormetazocine and phencyclidine: sensitization, cross-sensitization, and opioid antagonist activity.
The effects of phencyclidine (PCP) on locomotor activity were compared to those of the stereoisomers of N-allylnormetazocine (NAN) after acute administration to rats. PCP produced swaying and falling movements, increased sniffing behavior, and enhanced horizontal locomotor activity. d-NAN also induced swaying, falling, sniffing behavior and locomotion, and decreased rearing behavior. l-NAN decreased rearing activity, depressed locomotion, antagonized morphine antinociception and precipitated the morphine-withdrawal syndrome. Sensitization to drug-induced sniffing, rearing and locomotion developed after four daily injections of PCP, d-NAN or l-NAN in rats. Rats which were sensitized to PCP-induced locomotion, sniffing, and rearing were also cross-sensitized to both d-NAN and l-NAN. Animals sensitized to the effects of either d- or l-NAN exhibited cross-sensitization to PCP. There was little evidence that the cross-sensitization between the three agents was stereoselective. These data indicate that the acute effects of PCP are similar to those of d-NAN, but differ from l-NAN, the only agent of the three with opioid antagonist properties. The data further indicate that as sensitization to the motor effects develops during repeated administration of PCP, d-NAN or l-NAN, the differences among the three agents become less apparent.
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D008297:Male; D009021:Morphine Dependence / Q000209:etiology; D009043:Motor Activity / Q000187:drug effects; D009292:Narcotic Antagonists / Q000494:pharmacology*; D010620:Phenazocine / Q000031:analogs & derivatives* / Q000494:pharmacology; D010622:Phencyclidine / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013237:Stereoisomerism
D009292:Narcotic Antagonists; C012134:SK&F 10047; D010620:Phenazocine; D010622:Phencyclidine