An examination of the anticonvulsant properties of voltage-sensitive calcium channel inhibitors in amygdala kindled seizures.
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.
Mack
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CM
Mantech Environmental Technology Incorporated, Research Triangle Park, NC 27711.
Gilbert
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ME
D000679:Amygdala / Q000502:physiology*; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004569:Electroencephalography / Q000187:drug effects; D007696:Kindling, Neurologic / Q000502:physiology*; D008297:Male; D051381:Rats; D012640:Seizures / Q000517:prevention & control*
D000927:Anticonvulsants; D002121:Calcium Channel Blockers