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

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 micrograms/ml in AM-kindled rats and about 6 micrograms/ml in HIPP-kindled rats. The level of 6 micrograms/ml almost equals the therapeutic serum concentration of dapsone used in the treatment of leprosy.

Anticonvulsive effect of dapsone (4,4'-diaminodiphenyl sulfone) on amygdala-kindled seizures in rats and cats.

Dapsone (4,4'-diaminodiphenyl sulfone; DDS), an established anti-leprosy drug, showed anticonvulsive effects in the amygdaloid kindling model of epilepsy. Single doses of the drug in rats (6.25-12.5 mg/kg, i.p.) suppressed the kindled seizures in a dose-dependent manner without overt behavioral toxicity. With repeated oral administration in cats, relatively higher initial doses (13-23 mg/kg) were required to obtain seizure suppression, and neurotoxic signs occurred within a few days with serum drug levels of approximately 20 micrograms/ml. Although dapsone showed anticonvulsive effects in both animal species, the effective serum levels overlapped the toxic levels reported in the clinical treatment of leprosy. In the majority of the cats, however, seizure suppression was maintained even after the discontinuation of dapsone with lower serum levels than those observed at the beginning of the seizure suppression. Therefore, dapsone would be useful as an antiepileptic drug only when long-term anticonvulsive efficacy is demonstrated using smaller doses comparable to those used in the treatment of leprosy.