Stereoselective behavioral effects of N-allylnormetazocine in pigeons and squirrel monkeys

The behavioral effects of the stereoisomers of N-allylnormetazocine (NANM) were compared with those of phencyclidine (PCP) in pigeons and squirrel monkeys responding under a multiple fixed-interval fixed-ratio (FI FR) schedule of food presentation. Intermediate doses of (+)-NANM or PCP produced transient increases in FI responding in monkeys and sustained increases in FI responding in pigeons; higher doses decreased FI and FR responding in both species. In contrast to its enantiomer, (-)-NANM failed to increase FI responding significantly in either species; at high doses, (-)-NANM decreased FI and FR responding. In monkeys, (-)-NANM was about 10 times more potent than (+)-NANM in decreasing responding, whereas in pigeons (-)-NANM was about equipotent with (+)-NANM. In both species, (-)-NANM, but not (+)-NANM, antagonized the rate-decreasing effects of morphine on FI and FR responding. In monkeys, the effects of (-)-NANM, but not (+)-NANM or PCP, were antagonized by naloxone; the doses of naloxone required to antagonize the effects of (-)-NANM were more than 100 times higher than those required to antagonize the effects of morphine. In pigeons, naloxone did not systematically alter the effects of (-)-NANM, (+)-NANM or PCP. Haloperidol reduced or eliminated the increases in FI responding produced by intermediate doses of either (+)-NANM or PCP in pigeons, but did not antagonize the decreases in FI or FR responding produced by high doses of PCP or either stereoisomer of NANM. The results demonstrate a high degree of stereoselectivity in the behavioral effects of NANM. The levorotatory isomer had opioid-antagonist and non-opioid agonist effects in pigeons and mixed opioid agonist-antagonist effects in monkeys. The dextrorotatory isomer, on the other hand, had effects similar to those of PCP in both species.