NALOXONAZINE ANTAGONISM OF LEVORPHANOL-INDUCED ANTINOCICEPTION AND RESPIRATORY DEPRESSION IN RHESUS-MONKEYS

The mu-opioid receptor antagonist effects of naloxonazine on levorphan ol-induced thermal antinociception and respiratory depression were exa mined in rhesus monkeys, Levorphanol (0.032-3.2 mg/kg) produced dose-d ependent increases in tail-withdrawal latencies from 50 degrees C wate r in a warm-water tail-withdrawal assay and dose-dependent decreases i n ventilation in both air and 5% CO2 mixed in air. Naloxonazine (0.1-3 .0 mg/kg) antagonized both the antinociceptive and ventilatory effects of levorphanol to a similar degree, and the antagonist effects of nal oxonazine were greater after 1 h than after 24 h. Under all conditions , the antagonist effects of naloxonazine were fully surmountable. Schi ld analysis of the antagonist effects of naloxonazine after 1 h pretre atment in the antinociception assay yielded a pA(2) value of 7.6 and a slope of -0.50; by comparison, quadazocine yielded a pA(2) value of 7 .5 and a slope of -1.05. These results suggest that naloxonazine acts as a potent and fully reversible mu-opioid receptor antagonist with a moderately long duration of action in rhesus monkeys. In addition, the se results suggest that the antinociceptive and ventilatory effects of mu-opioid receptor agonists in rhesus monkeys are mediated by pharmac ologically similar populations of mu opioid receptors.