Voltage-sensitive
calcium (VSC) channels may contribute to epileptogenesis. A systematic examination of the
anticonvulsant efficacy of different classes of VSC channel inhibitors, however, is lacking in chronic seizure models. The present study evaluated representatives from three different classes of VSC channel inhibitors for their protection against amygdala kindled
seizures. Adult male rats (n = 12) were kindled to stage 5
seizures (GS), and a threshold intensity required to evoke a GS was determined. The Ca(++)-channel inhibitors (
verapamil 0, 10, 20, 40 mg/kg;
nimodipine 0, 5, 25, 50 mg/kg;
nitrendipine 0, 25, 50, 100 mg/kg and
flunarizine 0, 20, 40, 80 mg/kg) were administered 60-90 min prior to amygdala stimulation at the established threshold. None of the drugs altered threshold for inducing a seizure.
Verapamil, a phenylalkylamine, and the
dihydropyridines nimodipine and
nitrendipine were without effect on kindled
seizures. The diphenylalkylamine,
flunarizine, was found to be the most efficacious, reducing AD duration and duration of clonic seizure activity by more than 60% in most animals.
Flunarizine also decreased the severity of behavioral
seizures, with 40% of the animals displaying Stage 1-2
seizures only. It is concluded that some VSC Ca(++)-channel inhibitors do possess
anticonvulsant potential. Thus influx of extracellular
calcium through VSC channels may contribute to the expression of kindled
seizures.