title: Butorphanol-mediated antinociception in mice: partial agonist effects and mu receptor involvement.
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 approximately 10 times less potent in antagonizing the effect of U50,488H (average apparent pK(B) = 6.7). The selective mu antagonist beta-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), 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.
authors.affiliation: Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock 72205, USA.
authors.forename: H R
authors.initials: HR
authors.lastname: Garner
authors.forename: T F
authors.initials: TF
authors.lastname: Burke
authors.forename: C D
authors.initials: CD
authors.lastname: Lawhorn
authors.forename: J M
authors.initials: JM
authors.lastname: Stoner
authors.forename: W D
authors.initials: WD
authors.lastname: Wessinger
mesh_terms: D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D002077:Butorphanol / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009020:Morphine / Q000494:pharmacology; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology; D017450:Receptors, Opioid, mu / Q000819:agonists* / Q000502:physiology
chemical_list: D000701:Analgesics, Opioid; D011759:Pyrrolidines; D017450:Receptors, Opioid, mu; C051844:norbinaltorphimine; D009271:Naltrexone; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; C024524:beta-funaltrexamine; D009020:Morphine; C055382:naltrindole; D002077:Butorphanol