Suppression of focal epileptiform discharges by intraventricular perfusion of a calcium antagonist.

Calcium currents were found to participate in the generation of epileptic discharges of single cortical neurones. The present experiments tested whether a systemic administration of a calcium antagonist is able to influence epileptic activity in neuronal populations. Focal interictal epileptiform discharges (FIEDs) were elicited by application of penicillin to the motor cortex of the rat. The calcium antagonist verapamil dissolved in artificial cerebrospinal fluid was applied by intraventricular push-pull perfusion to achieve high concentrations of the drug in cerebral tissue and to avoid alterations of the systemic circulatory system. The application of the calcium antagonist reduced FIEDs in amplitude and in frequency of occurrence. In some experiments the suppression of seizure activity was preceded by a transient enhancement. After termination of the drug perfusion FIEDs were often re-established. Control experiments revealed that perfusion with drug-free cerebrospinal fluid did not change FIEDs. In experiments without epileptic activity, cortical evoked potentials elicited by stimulation of the sciatic nerve tended to increase with perfusion of the calcium antagonist. As a whole, the systemic administration of the calcium antagonist verapamil depressed FIED and exerted an inverse effect on synchronized non-epileptic neuronal activity.