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Abstract

Kappa opioid antagonist effects of systemically administered nor-binaltorphimine in a thermal antinociception assay in rhesus monkeys.

E R Butelman, S S Negus, Y Ai, B R de Costa and J H Woods
Journal of Pharmacology and Experimental Therapeutics December 1993, 267 (3) 1269-1276;
E R Butelman
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S S Negus
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Y Ai
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B R de Costa
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J H Woods
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Abstract

The effects of subcutaneously administered nor-binaltorphimine (nor-BNI; 1.0 and 3.2 mg/kg) were examined in the warm-water (50 degrees C and 55 degrees C) tail-withdrawal assay in rhesus monkeys (n = 3). Nor-BNI alone produced variable antinociceptive effects in 50 degrees C water up to 3.5 hr after administration but was completely ineffective against the 55 degrees C stimulus. Pretreatment with nor-BNI under conditions where it was devoid of antinociceptive effects produced rightward shifts in dose-effect curves for the kappa opioid agonist U50,488 for as long as 14 and 21 days after 1.0 and 3.2 mg/kg of nor-BNI, respectively. Under conditions when U50,488 dose-effect curves were shifted, nor-BNI (3.2 mg/kg) also caused rightward shifts in the antinociceptive dose-effect curves of the kappa agonist U69,593 but not in those of the mu agonist alfentanil or the kappa agonists [5R-(5,7,8,beta)]N-methyl-N-[7- (1-pirrolidinyl)1-oxaspiro[4,5]dec-8-yl]4-benzofuranaceta mide, bremazocine, ethylketocyclazocine and Mr2033. It is concluded that under the present conditions, nor-BNI acts as a selective kappa opioid antagonist with an extremely long duration of action. These findings are also consistent with the notion that nor-BNI may antagonize only compounds acting at a subtype of kappa opioid receptor.

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Journal of Pharmacology and Experimental Therapeutics
Vol. 267, Issue 3
1 Dec 1993
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Abstract

Kappa opioid antagonist effects of systemically administered nor-binaltorphimine in a thermal antinociception assay in rhesus monkeys.

E R Butelman, S S Negus, Y Ai, B R de Costa and J H Woods
Journal of Pharmacology and Experimental Therapeutics December 1, 1993, 267 (3) 1269-1276;

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Abstract

Kappa opioid antagonist effects of systemically administered nor-binaltorphimine in a thermal antinociception assay in rhesus monkeys.

E R Butelman, S S Negus, Y Ai, B R de Costa and J H Woods
Journal of Pharmacology and Experimental Therapeutics December 1, 1993, 267 (3) 1269-1276;
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