Propofol exhibits antiepileptic activity in hippocampal pyramidal neurons

Propofol was reported to exhibit an antiepileptic activity. This study was performed to investigate the effect of propofol on evoked and spontaneous seizure-like activity induced by the convulsant veratridine. Studies were performed on rat brain slices using conventional electrophysiological intracellular techniques. The alteration of sodium channel function by veratridine (0.3 microM) induced an evoked and spontaneous seizure-like activity in the hippocampal CA1 pyramidal neurons. Therapeutic concentrations of propofol (10 microM) were ineffective in inhibiting veratridine-induced seizure-like activity. However, higher concentrations (50-100 microM, n=6) inhibited both evoked and spontaneous bursting, induced by veratridine. The inhibitory effect of propofol (100 microM) was associated with membrane hyperpolarization [after veratridine, -66+/-0.71 mV (mean+/-S.E.M.), and after propofol, -77+/-2.15 mV] and with an increase in input resistance [after veratridine (37.8+/-1.2 MOmega) and after propofol (43+/-1.3 MOmega)]. The drug also produced an increase in current threshold. Results from this study are valuable in solving critical questions regarding the antiepileptic activity of propofol and strengthen the validity of the veratridine model in testing for potential antiepileptic drugs.