Anticonvulsant effects of dihydropyridine Ca2+ antagonists in electrocortical shock seizures

Abstract

The dihydropyridine calcium antagonists nimodipine (NMD), PN200-110, and nicardipine were compared with phenytoin (PHT) as potential anticonvulsants in electrocortical shock (ECS)-induced seizures in the white New Zealand rabbit. Before treatment, seizure duration ranged from 43.8 +/- 5.1 to 49.6 +/- 5.2 s with an ECS stimulus of 10-V, 100-Hz, 0.1-ms pulses for 5 s. Each drug was administered into the right internal intracarotid artery 2 min before the ECS. A cumulative nimodipine dose of 440 micrograms/kg decreased seizure discharge to 6.6 +/- 5.0 s (p less than 0.001), whereas a total dose of 1.0 mg/kg PN200-110 was required to achieve a similar effect. Nicardipine was ineffective. A cumulative dose of 7 mg/kg phenytoin was required to suppress seizure discharge. These results indicate that Ca2+ channels modulated by dihydropyridines play a facilitating role in ECS-induced seizures. We propose that the anticonvulsant effects of nimodipine and PN200-110 are due to inhibition of neuronal calcium L-channels. Dihydropyridine Ca2+ antagonists that penetrate the blood-brain barrier (BBB) and bind to neuronal tissue may emerge as a novel class of anticonvulsants.