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Abstract

Mu antagonist and kappa agonist properties of beta-funaltrexamine (beta-FNA) in vivo: long-lasting spinal analgesia in mice.

J A Qi, J S Heyman, R J Sheldon, R J Koslo and F Porreca
Journal of Pharmacology and Experimental Therapeutics March 1990, 252 (3) 1006-1011;
J A Qi
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J S Heyman
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R J Sheldon
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R J Koslo
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F Porreca
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Abstract

It is now well established that compounds classified as kappa opioids can, in circumstances where they produce no measurable agonist effects, antagonize the actions of mu opioids. Largely on the basis of studies in vitro, beta-funaltrexamine (beta-FNA) has been classified as a reversible kappa agonist and long acting mu antagonist. The present study investigated the possibility that the mu antagonist profile of this compound could be related to its kappa agonist actions. We used two tests of analgesia (the acetic acid writhing test and the hot-water tail-flick test) and selective kappa agonists and antagonists given at supraspinal and spinal sites in mice. Intrathecal (i.t.) administration of beta-FNA, but not the selective kappa agonist U50,488H, produced long-lasting and dose-related analgesia in the writhing test for periods up to 48 hr after a single dose. In contrast, i.t. beta-FNA had no agonist actions in the tail-flick test. The kappa antagonist, nor-binaltorphimine (nor-BNI) produced no agonist effects in either analgesic test when given i.t. In the writhing test, nor-BNI produced a rightward displacement of the beta-FNA dose-response line regardless of whether beta-FNA was given 10 min or 4 hr before testing, indicating that i.t. beta-FNA was acting as a kappa agonist in this test. As both i.t. morphine and beta-FNA are active in the writhing test, the antagonist actions of i.t. beta-FNA could be evaluated only in the tail-flick test. beta-FNA, but not nor-BNI, blocked the effects of i.t. morphine in the tail-flick test.(ABSTRACT TRUNCATED AT 250 WORDS)

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Journal of Pharmacology and Experimental Therapeutics
Vol. 252, Issue 3
1 Mar 1990
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Abstract

Mu antagonist and kappa agonist properties of beta-funaltrexamine (beta-FNA) in vivo: long-lasting spinal analgesia in mice.

J A Qi, J S Heyman, R J Sheldon, R J Koslo and F Porreca
Journal of Pharmacology and Experimental Therapeutics March 1, 1990, 252 (3) 1006-1011;

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Abstract

Mu antagonist and kappa agonist properties of beta-funaltrexamine (beta-FNA) in vivo: long-lasting spinal analgesia in mice.

J A Qi, J S Heyman, R J Sheldon, R J Koslo and F Porreca
Journal of Pharmacology and Experimental Therapeutics March 1, 1990, 252 (3) 1006-1011;
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