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Research ArticleArticle

κ-Opioid Receptor Effects of Butorphanol in Rhesus Monkeys

Jeffrey A. Vivian, Michael B. DeYoung, Tina L. Sumpter, John R. Traynor, John W. Lewis and James H. Woods
Journal of Pharmacology and Experimental Therapeutics July 1999, 290 (1) 259-265;
Jeffrey A. Vivian
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Michael B. DeYoung
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Tina L. Sumpter
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John R. Traynor
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John W. Lewis
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James H. Woods
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Abstract

Butorphanol and nalbuphine have substantial affinity for μ and κ-opioid receptor sites, yet their behavioral effects in monkeys are largely consistent with a μ receptor mechanism of action. Using ethylketocyclazocine (EKC) discrimination and diuresis assays in rhesus monkeys (Macaca mulatta), the purpose of the current investigation was to characterize the in vivo κ-opioid activity of these compounds through the use of an insurmountable μ-opioid receptor antagonist, clocinnamox. Alone, butorphanol (0.001–0.032 mg/kg i.m.) failed to generalize to EKC, and pretreatment with the competitive opioid receptor antagonist quadazocine (0.1 or 0.32 mg/kg i.m.) did not alter this generalization. At 24 h after clocinnamox (0.1 mg/kg i.m.) administration, butorphanol fully generalized to EKC, and this generalization was maintained in two of three monkeys at 72 h. Parallel results were observed in diuresis: butorphanol alone and in the presence of quadazocine (1 mg/kg i.m.) did not alter urine output, and a marked diuretic effect was demonstrated 24 h to 2 weeks after clocinnamox administration. Clocinnamox did not alter the discriminative stimulus or diuretic effects of nalbuphine or of the κ-opioid receptor agonists EKC or U69593. These results are consistent with an in vivo agonist activity of butorphanol at κ-opioid receptors that can only be demonstrated when an insurmountable antagonist has substantially eliminated the dominant receptor population through which it exerts its action.

Footnotes

  • Send reprint requests to: J. A. Vivian, Ph.D., Department of Pharmacology, University of Michigan Medical School, 1301 Medical Science Research Building III, Ann Arbor, MI 49109. E-mail: jvivian{at}umich.edu

  • ↵1 This work was supported by U.S. Public Health Service Grants DA00254, DA07268, and DA05773. Portions of this research were presented at the Annual Meeting of the College on Problems of Drug Dependence, Nashville, TN, 1997.

  • Abbreviations:
    EKC
    ethylketocyclazocine
    FR
    fixed-ratio
    U50488
    (trans)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolindinyl)-cyclohexyl]benzeneacetamide
    U69593
    (+)-(5α,7α,8β)-N-methyl-N-[7-(1-pyrrolidinyl)-1-oxaspiro[4,5]dec-8-yl]-benzeneacetamide
    • Received September 15, 1998.
    • Accepted March 2, 1999.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 290 (1)
Journal of Pharmacology and Experimental Therapeutics
Vol. 290, Issue 1
1 Jul 1999
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Research ArticleArticle

κ-Opioid Receptor Effects of Butorphanol in Rhesus Monkeys

Jeffrey A. Vivian, Michael B. DeYoung, Tina L. Sumpter, John R. Traynor, John W. Lewis and James H. Woods
Journal of Pharmacology and Experimental Therapeutics July 1, 1999, 290 (1) 259-265;

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Research ArticleArticle

κ-Opioid Receptor Effects of Butorphanol in Rhesus Monkeys

Jeffrey A. Vivian, Michael B. DeYoung, Tina L. Sumpter, John R. Traynor, John W. Lewis and James H. Woods
Journal of Pharmacology and Experimental Therapeutics July 1, 1999, 290 (1) 259-265;
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