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.
Ishida
S
S
National Epilepsy Center, Shizuoka Higashi Hospital, Japan.
Hamada
K
K
Yagi
K
K
Seino
M
M
D000679:Amygdala / Q000187:drug effects* / Q000503:physiopathology; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D003622:Dapsone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography / Q000187:drug effects; D005071:Evoked Potentials / Q000187:drug effects / Q000502:physiology; D006624:Hippocampus / Q000187:drug effects* / Q000503:physiopathology; D007696:Kindling, Neurologic / Q000187:drug effects* / Q000502:physiology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012640:Seizures / Q000503:physiopathology*
D000927:Anticonvulsants; D003622:Dapsone