CONVULSIVE EFFECTS OF SYSTEMIC ADMINISTRATION OF THE DELTA-OPIOID AGONIST BW373U86 IN MICE

A systemically active, nonpeptidic delta receptor-selective agonist, p iperazinyl)-3-hydroxybenzyl)-N,N-diethylbenzamide (BW373U86), produced a brief, nonlethal convulsion in mice. The behavioral pattern of conv ulsion produced by pentylenetetrazol was similar to that produced by s ystemic administration of BW373U86. Although several episodes of convu lsion occurred with pentylenetetrazol, BWB373U86 produced a single, br ief 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-depend ent rightward shifts in the potency of BW373U86 to induce a convulsion . A dose of 3.2 mg/kg of midazolam completely eliminated convulsions i nduced by BW373U86. Midazolam (0.32 and 3.2 mg/kg), but not naltrindol e (3.2 and 32.0 mg/kg), produced parallel rightward shifts in the pent ylenetetrazol dose-effect curve. Pretreatment with a single injection of BW373U86 (3.2, 10.0, 32.0 or 100 mg/kg) produced a dose-related red uction in the capacity of BW373U86 to induce a second convulsion. Reco very of sensitivity to BW373U86 did not return to control levels for u p 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 1 0.0 mg/kg of BW373U86 prevent ed the refractoriness (tolerance) induced by the single dose of BW373U 86. These data suggest that the convulsions as well as the tolerance i nduced by BW373U86 were initiated through delta opioid receptors.