BUTORPHANOL-MEDIATED ANTINOCICEPTION IN MICE - PARTIAL AGONIST EFFECTS AND MU-RECEPTOR INVOLVEMENT

In the present experiments, we characterized the agonist and antagonis t effects of butorphanol in mice. In the mouse radiant-heat tail-flick test, the mu agonists morphine and fentanyl and the kappa agonist U50 ,488H were fully effective as analgesics, whereas butorphanol was part ially effective (producing 82% of maximal possible analgesic effect). Naltrexone was approximately equipotent in antagonizing the effects of morphine, fentanyl and butorphanol; in vivo apparent pA(2) values for these naltrexone/agonist interactions were 7.5 (unconstrained). Naltr exone was similar to 10 times less potent in antagonizing the effect o f U50,488H (average apparent pK(B) = 6.7). The selective mu antagonist beta-funaltrexamine (0.1-1.0 mg/kg) antagonized the effects of butorp hanol in a dose-dependent insurmountable manner. Pretreatment with nor -binaltorphimine (32 mg/kg), a kappa-selective antagonist, did not rel iably antagonize butorphanol, and naltrindole (20 and 32 mg/kg), a del ta-selective antagonist, failed to antagonize the effects of butorphan ol. Low doses of butorphanol (1.0, 1.8 or 3.2 mg/kg) caused parallel, rightward shifts in the dose-effect curve for morphine and parallel le ftward shifts in the dose-effect curve for U50,488H. Taken together, t he results of the present study suggest that butorphanol is a partial agonist in the mouse radiant-heat tail-flick test and that activity at mu receptors accounts for the majority of its antinociceptive effects .