Convulsive effects of systemic administration of the delta opioid agonist BW373U86 in mice

S. D. Comer, E. M. Hoenicke, A. I. Sable, R. W. McNutt, K. J. Chang, B. R. De Costa, H. I. Mosberg, J. H. Woods

Research output: Contribution to journalArticle

126 Scopus citations

Abstract

A systemically active, nonpeptidic delta receptor-selective agonist, (±)- 4-((α-R*)-α-((2S*,5R*)-4-allyl-2,5-dimethyl-1-piperazinyl)-3- hydroxybenzyl)-N,N-diethylbenzamide (BW373U86), produced a brief, nonlethal convulsion in mice. The behavioral pattern of convulsion produced by pentylenetetrazol was similar to that produced by systemic administration of BW373U86. Although several episodes of convulsion occurred with pentylenetetrazol, BW373U86 produced a single, brief episode. Naltrexone (10.0 and 100 mg/kg) and naltrindole (1.0, 3.2 and 10.0 mg/kg), but not midazolam (0.32 mg/kg), produced dose-dependent rightward shifts in the potency of BW373U86 to induce a convulsion. A dose of 3.2 mg/kg of midazolam completely eliminated convulsions induced by BW373U86. Midazolam (0.32 and 3.2 mg/kg), but not naltrindole (3.2 and 32.0 mg/kg), produced parallel rightward shifts in the pentylenetetrazol dose-effect curve. Pretreatment with a single injection of BW373U86 (3.2, 10.0, 32.0 or 100 mg/kg) produced a dose-related reduction in the capacity of BW373U86 to induce a second convulsion. Recovery of sensitivity to BW373U86 did not return to control levels for up to 2 weeks after pretreatment with a single injection of 32.0 mg/kg of BW373U86. Naltrindole (3.2 mg/kg) administered within 1 hr, but not at 2 hr, after a pretreatment dose of 10.0 mg/kg of BW373U86 prevented the refractoriness (tolerance) induced by the single dose of BW373U86. These data suggest that the convulsions as well as the tolerance induced by BW373U86 were initiated through delta opioid receptors.

Original languageEnglish (US)
Pages (from-to)888-895
Number of pages8
JournalJournal of Pharmacology and Experimental Therapeutics
Volume267
Issue number2
StatePublished - Jan 1 1993
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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