[On the mechanism of action of valproid acid]

In mice, the influence of valproic acid (di-n-propylacetate, DPA) on central level of gamma-aminobutyric acid (GABA) as well as the activity of the enzymes regulating GABA metabolism, glutamate decarboxylase (GAD) and GABA-alpha-oxoglutarate aminotransferase (GABA-T) were studied. It was shown that the elevation of GABA by DPA was accompanied by an activation of GAD. GABA-T was inhibited only by toxic doses or high concentrations of DPA in vivo and in vitro, and so was GAD. DPA proved able to antagonize the biochemical alterations induced by convulsant doses of isoniazid, i.e., decreases in the level of GABA and the activity of GAD. These results point to a role of the transmitter pool of GABA regulated by GAD in the anticonvulsant effect of DPA.