Naloxonazine antagonism of levorphanol-induced antinociception and respiratory depression in rhesus monkeys.
Eur J Pharmacol, 1996/2/29;298(1):31-6.
Gatch MB[1], Liguori A, Negus SS, Mello NK, Bergman J, Liguori T
Affiliations
PMID: 8867916
Impact factor: 5.195
Abstract
The mu-opioid receptor antagonist effects of naloxonazine on levorphanol-induced thermal antinociception and respiratory depression were examined in rhesus monkeys. Levorphanol (0.032-3.2 mg/kg) produced dose-dependent increases in tail-withdrawal latencies from 50 degrees C water in a warm-water tail-withdrawal assay and dose-dependent decreases in 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 naloxonazine were greater after 1 h than after 24 h. Under all conditions, the antagonist effects of naloxonazine were fully surmountable. Schild analysis of the antagonist effects of naloxonazine after 1 h pretreatment in the antinociception assay yielded a pA2 value of 7.6 and a slope of -0.50; by comparison, quadazocine yielded a pA2 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, these results suggest that the antinociceptive and ventilatory effects of mu-opioid receptor agonists in rhesus monkeys are mediated by pharmacologically similar populations of mu opioid receptors.
MeSH terms
Analgesia; Analgesics, Opioid; Animals; Dose-Response Relationship, Drug; Levorphanol; Macaca mulatta; Naloxone; Narcotic Antagonists; Respiration; Respiratory Insufficiency
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