Examination of the potential antiepileptic activity of calcium antagonists with different sites of action

Abstract

1. 1. Calcium is proposed to play a role in the genesis of epileptic seizures, and a number of established antiepileptic drugs limit the transport of extracellular calcium into neuronal cells. 2. 2. The aim of the present study was to explore the potential antiepileptic activity of three calcium antagonists: nifedipine (20 mg/kg i.p.), which blocks the calcium channel at its outer mouth; verapamil (30 mg/kg i.p.), which blocks the calcium channel at its inner mouth; and propyl-methylenedioxyindene (pr-MDI; 68, 100 and 120 mg/kg i.p.), which acts intracellularly to inhibit calcium mobilization from the endoplasmic reticulum. 3. 3. In the maximal electroshock test, none of the calcium antagonists provided protection against tonic seizures in mice. Phenytoin (20 mg/kg i.p.), on the other hand, afforded complete protection. 4. 4. In the pentylenetetrazol-induced seizure test, the order of effectiveness of the three calcium antagonists in attenuating the severity of the clonic and tonic seizures in mice was: nifedipine > verapamil > pr-MDI. All three calcium antagonists were less effective than ethosuximide (200 mg/kg i.p.). 5. 5. These findings indicate that the calcium antagonists would be of no value in the treatment of grand mal epilepsy, while only those agents acting at the outer side of the membrane would have limited usefulness at best against petit mal seizures.