Biphasic electrophysiological effects of phenytoin on neural tissue cultures

Cerebellar and cerebral neocortical explants were exposed to concentrations of phenytoin (DPH) ranging from 2 to 22.5 micrograms/ml of buffered balanced salt solution while extracellular electrical activity was recorded. DPH applied to cerebellar cultures produced a biphasic effect on cortical spontaneous activity, with an initial excitatory phase followed by more sustained suppression. The duration of each of these phases was dose dependent. A similar biphasic effect of DPH on stimulus-elicited responses in cultures of cerebral neocortex was noted. An enhancement of the amplitudes of these responses and prolonged oscillatory afterdischarges were early consequences of DPH application. After variable intervals up to 1/2 hour later, there was a prolonged attenuation of these responses. The initial excitatory effect of DPH demonstrated upon direct application to neurons in culture raises the possibility that intravenous DPH may not be the most appropriate drug for the rapid treatment of status epilepticus in man.