Action mechanisms of sodium valproate

Sodium valproate (VPA) is thought to counteract cell hyperexcitability either by enhancing the GABA-mediated inhibition or by affecting voltage dependent membrane ionic currents. Relevant to the first hypothesis are: 1) the demonstration of an inhibitory effect of VPA on the catabolic enzyme GABA-transaminase leading to an increase of the presynaptic pool of GABA; 2) the evidence of a potentiation of the postsynaptic action of GABA. The second hypothesis is supported by a VPA-induced reduction of Na⁺ (and Ca⁺⁺) inward currents with a reciprocal enhancement of Ca⁺⁺ dependent K⁺ outward currents. The actual correspondence of the active concentration in experimental and clinical studies make difficult at present to define the ultimate action mechanism accounting for the well established antiepileptic effect of VPA.