Flunarizine--its effect on pentylenetetrazol-kindled seizures and on related cognitive disturbances

Epileptics are often faced with impaired intellectual processes. The basis of these impairments is still poorly understood. Kindling is an accepted model for the study of the convulsive component of epilepsy. Furthermore, it was demonstrated that pentylenetetrazol-kindled rats show diminished shuttle-box learning. Therefore, we used this model to study the influence of flunarizine, a calcium antagonist, on kindled seizures as well as related learning impairments. It was found, that acutely administered flunarizine significantly suppressed the expression of kindled seizures, but there was no effect on the developmental character of kindling. Moreover, the substance had an anticonvulsant action when administered after completion of kindling. The learning ability of kindled rats was significantly augmented when flunarizine was injected prior to each convulsive stimulation or when administered after completion of kindling. The results were explained in terms of interactions of a depressive effect on abnormal neuronal excitation, a protection against calcium-induced neurotoxicity and, finally, the vascular effect of flunarizine.