Suppression of recurrent generalized tonic-clonic seizure discharges by intraventricular perfusion of a calcium antagonist.

Epileptic depolarizations in single motor cortical and hippocampal neurons and focal epileptic discharges in neuronal cortical populations have been described to be decreased by calcium antagonists. In the present investigations the action of the calcium antagonist verapamil on generalized tonic-clonic seizures was studied. The experiments were performed in the anesthetized and artificially ventilated rat. Tonic-clonic seizures were induced by repeated intraperitoneal injections of pentylenetetrazol (PTZ). The calcium antagonist verapamil, dissolved in artificial cerebrospinal fluid, was applied to a lateral cerebral ventricle by means of the push-pull technique. This procedure achieved high concentrations of the drug in cerebral tissue and avoided alterations of the systemic circulatory system. Generalized tonic-clonic seizures were depressed in intensity to a great extent and often abolished during the verapamil perfusion. With this suppression seizures decreased in their rate of occurrence. The negative shift of the epicortical DC potential evoked by the PTZ injections before verapamil application became a positive displacement during verapamil perfusion. Control experiments revealed (i) that intraventricular perfusion with drug-free cerebrospinal fluid did not change tonic-clonic seizure activity, and (ii) that in experiments without epileptic activity verapamil perfusion exerted no depressive effect on the power of the spontaneous EEG and failed to shift the DC potential to the positive side. As a whole, systemic administration of the calcium antagonist verapamil depressed tonic-clonic seizures and did not depress non-epileptic cerebral activity.