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 pKB = 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.
Footnotes
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Send reprint requests to: Dr. William D. Wessinger, University of Arkansas for Medical Sciences, Department of Pharmacology and Toxicology, Slot 611, 4301 W. Markham Street, Little Rock, AR 72205. E-mail: wdwessinger{at}life.uams.edu
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↵1 A preliminary report of these findings was presented at the International Anesthesiology Research Society (IARS) meeting in Washington, DC, March 1996.
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↵2 This study was supported by the Division of Pediatric Anesthesia, Department of Anesthesiology, University of Arkansas for Medical Sciences, Little Rock, AR, and the UAMS Graduate Student Research Fund. H.R.G. was supported by a predoctoral fellowship funded by NIDA Training Grant DA07260.
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↵3 Present address: Johns Hopkins University School of Medicine, Behavioral Pharmacology Research Unit, 5510 Nathan Shock Dr., Suite 3000, Baltimore, MD 21224.
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↵4 Present address: Astra Merck, Inc., 3838 N. Causeway Blvd., Lakeway III, Ste. 2400, Metairie, LA 70002.
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↵5 Present address: 4401 Heritage Dr., Lawrence, KS 66047.
- Abbreviations:
- %MPE
- % maximum possible effect
- β-FNA
- β-funaltrexamine
- nor-BNI
- nor-binaltorphimine
- CL
- confidence limit
- Received November 20, 1996.
- Accepted May 23, 1997.
- The American Society for Pharmacology and Experimental Therapeutics
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