[Functional implication of calcium ions in epileptic seizures. Antiepileptic effects of organic calcium antagonists].

In animal experiments, focal epileptic activity and tonic-clonic seizures were induced by local application of penicillin and repeated intraperitoneal injections of pentetrazol (PTZ), respectively. With epileptic activity neocortical and hippocampal neurons showed typical paroxysmal depolarization shifts. Experimental findings indicate that a calcium inward current and calcium dependent membrane currents participate in the generation of these events. Paroxysmal depolarizations were depressed by intra- and extracellular applications of the organic calcium channel blockers N,N-dimethyl-N-(4-cyan-4-(3,4,5-trimethoxyphenyl)-5-methyl-hexyl)- N-(beta- 3,4-dimethoxyphenylethyl)-ammonium-chloride-monohydrate (D 890) and verapamil. The same depressive effect was exerted by flunarizine in hippocampal but not in neocortical neurons. Paroxysmal depolarizations were enhanced by intracellular injections of the calcium agonist methyl 1,4-dihydro-2,6-dimethyl-3-nitro-4-(2-trifluoromethylphenyl)-pyridine-5- carboxylate (Bay K 8644) and of the calcium chelator ethyleneglycol-bis(aminoethylether)N,N,N',N'-tetraacetate (EGTA). Focal seizure activity of the neocortex was reduced and often abolished by intracerebroventricular perfusion of verapamil, with the frequency of occurrence of epileptic discharges being decreased. Generalized tonic-clonic seizures were depressed to a great extent and often abolished during an intracerebroventricular verapamil perfusion. Simultaneously, the negative shift of the DC potential evoked by the PTZ injections turned over to a positive displacement. In non-epileptic preparations, organic calcium antagonists had no depressive effects on neuronal bioelectrical activity.