Comparing the anticonvulsive effects of dapsone on amygdala-kindled seizures and hippocampal-kindled seizures in rats

Abstract

Dapsone, an antileprosy drug, was administered to rats with amygdala (AM)‐kindled seizures or hippocampal (HIPP)‐kindled seizures to elucidate its anticonvulsive efficacy. Adult male Wistar rats were subjected to kindling stimulations 2 weeks after electrode‐implantation. The subjects were tested once a day for 7 successive days after inducing three generalized (stage 5) seizures to study the effects of dapsone. Dapsone had an inhibitory effect on stage 5 seizures at 12.50 mg/kg in the AM‐kindled rats and at 6.25 mg/kg and 9.375 mg/kg in the HIPP‐kindled rats. Thus, there was a distinct difference in the effective dose for generalized seizures between the AM‐kindled rats and the HIPP‐kindled rats. The inhibitory action of dapsone on stage 5 seizures may be due mainly to the elevation of the afterdischarge‐triggering threshold at the stimulation site of the AM or HIPP. Such inhibitory action appears prominently at serum concentrations of about 13 μg/ml in AM‐kindled rats and about 6 μg/ml in HIPP‐kindled rats. The level of 6 μg/ml almost equals the therapeutic serum concentration of dapsone used in the treatment of leprosy.