Butorphanol-mediated antinociception in mice: Partial agonist effects and Mu receptor involvement

H. R. Garner, Timothy F. Burke, C. David Lawhorn, Joanne M. Stoner, William D. Wessinger

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32 Scopus citations

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 the kappa 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 pA2 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 selective mu antagonist β-funaltraxamine (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), a delta-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.

Original languageEnglish (US)
Pages (from-to)1253-1261
Number of pages9
JournalJournal of Pharmacology and Experimental Therapeutics
Volume282
Issue number3
StatePublished - Sep 1 1997

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ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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