The antiepileptic effects of the organic calcium channel blocker verapamil were tested in non-drug-induced epileptiform activities. Low Mg2+ epileptic field potentials (EFP) were elicited in hippocampal slices of guinea pigs. Verapamil reduced frequency of occurrence and amplitude of EFP until EFP failed. The EFP reappeared if verapamil was withdrawn from low Mg2+ solution. Elevating the KCl concentration from 4 to 8 mM resulted in shortening of the latency of EFP abolition by verapamil and prolongation of the depressive effects of verapamil following its withdrawal. The findings indicate that transmembraneous calcium fluxes play also an essential role in low Mg(2+)-induced epileptiform activities.

Animal experiments show that calcium currents essentially participate in epileptogenesis. Thus, epileptiform field potentials (EFP) were suppressed by organic calcium antagonists. Present investigations tested whether such an antiepileptic calcium antagonism also exists in human cerebral tissue. Experiments were performed on slices (400 mum) of human neocortex. Tissue used was a small portion of that which is normally removed for the treatment of brain tumor. Epileptiform activity was induced by superfusion with Mg2+-free cerebrospinal fluid (CSF). Verapamil (40 or 60 mumol/L) was added to the Mg2+-free CSF. Superfusion with Mg2+-free CSF induced epileptiform activity in the slices within half an hour. The EFP consisted of spikes or spike-wave complexes. The mean frequency of occurrence was 10 EFP/min. Application of verapamil led to an abolition of EFP within 1 and 2 h with 60 and 40 mumol/L verapamil, respectively. The suppressive effect was often preceded by a transient increase of frequency of occurrence of EFP. During washout of the organic calcium antagonist, EFP reappeared within 10 min. The observed antiepileptic calcium antagonism may offer the chance of a new strategy in pharmacotherapy of the epilepsies.