Is the anticonvulsant mechanism of valproate linked to its interaction with the cerebral γ-hydroxybutyrate system?

Abstract

There is now evidence that γ-hydroxybutyrate (GHB) may be a neuromodulator in the CNS. Administration of this compound to various mammals at sub-anaesthetic doses induces brain electrical activity resembling that of human absence epilepsy. This effect is antagonized by the anticonvulsant drugs valproate and ethosuximide, and by the opiate antagonist naloxone. In vitro valproate and ethosuximide reduce the depolarization-induced release of GHB from rat hippocampal slices, and in vivo valproate antagonizes the increase in hippocampal cGMP levels induced by prior GHB administration. Michel Maitre and colleagues therefore propose that the anticonvulsant action of valproate may be linked to its interaction with the endogenous GHB system.