Valproate suppresses N-methyl-D-aspartate-evoked, transient depolarizations in the rat neocortex in vitro.

Effects of the antiepileptic drug sodium valproate (VPA) were studied on neocortical pyramidal cells (layer II/III) of the rat in vitro by intracellular recording. VPA (0.1-1 mM) in a dose-related manner suppressed the characteristic transient depolarizations induced by N-methyl-D-aspartate (NMDA) applied iontophoretically Higher concentrations of VPA (5-10 mM) also reduced L-glutamate responses. At these concentrations VPA increased the duration of orthodromically evoked inhibitory postsynaptic potentials and reduced repetitive spike firing induced by depolarizing currents. All effects were fully reversible within about 30 min. These results suggest that an essential mode of action for the anticonvulsant VPA is the attenuation of NMDA receptor-mediated excitation.