Anticonvulsant Action of Fluzinamide (AHR‐8559) on Kindled Amygdaloid Seizures

Abstract

The anticonvulsant properties of fluzinamide (AHR-8559 [N-methyl-3-[3-(trifluoromethyl)phenoxy]-1-azetidine carboxamide]) were evaluated in the kindled amygdaloid seizure model in rats. Fluzinamide significantly attenuated afterdischarge durations and the severity of the accompanying convulsive responses in previously kindled rats at doses that did not cause sedation or ataxia. After acute i.p. injections, the maximum anticonvulsant effectiveness against suprathreshold (400 .mu.A) stimulation was seen at 30 min. Fluzinamide (10-80 mg/kg i.p.) was also evaluated in previously kindled rats using threshold (20 .mu.A increments) seizures. Low doses of fluzinamide significantly elevated seizure threshold and reduced both elicited afterdischarge durations and seizure severity. When administered daily during kindling acquisition, fluzinamide (20 and 40 mg/kg i.p.) significantly increased the number of trials necessary to complete kindling. The duration and the severity of the responses induced by stimulations during the acquisition period were reduced. Studies had shown that the anticonvulsant profile for fluzinamide, as determined by traditional electrical and clinical models of epilepsies, most closely resembled phenobarbital and valproic acid, and differed from phenytoin and ethosuximide. This study is consistent with this profile, with fluzinamide-like phenobarbital and valproic acid, significantly modifying both acquisition of kindling and the fully kindled amygdaloid seizure.