Abstract

In the present experiments, we characterized the agonist and antagonist effects of butorphanol in mice. In the mouse radiant-heat tail-flick test, the mu agonists morphine and fentanyl and thekappa agonist U50,488H were fully effective as analgesics, whereas butorphanol was partially 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). Naltrexone was ∼10 times less potent in antagonizing the effect of U50,488H (average apparent pK_B = 6.7). The selectivemu antagonist β-funaltrexamine (0.1–1.0 mg/kg) antagonized the effects of butorphanol in a dose-dependent insurmountable manner. Pretreatment with nor-binaltorphimine (32 mg/kg), a kappa-selective antagonist, did not reliably antagonize butorphanol, and naltrindole (20 and 32 mg/kg), adelta-selective antagonist, failed to antagonize the effects of butorphanol. 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 leftward shifts in the dose-effect curve for U50,488H. Taken together, the 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.