Molecular Mechanisms of Valproic Acid Action on Signalling Systems and Brain Functions

Abstract

Valproic acid (valproate, VA) has been widely used as an antiepileptic agent for several decades, as well as in the treatment of bipolar affective disorder. For many years, the ability of VA to stop epileptic seizures of a different nature has been associated with increased GABAergic neurotransmission, inhibition of glutamatergic neurotransmission and a general decrease in CNS hyperactivity by acting on ion channels, however precise mechanisms of VA anticonvulsant effects are still not clear. Over time, the effects of VA on other neurotransmitter systems, enzymes and intracellular signalling pathways have been revealed, however they do not explain the effectiveness of the drug as an anticonvulsant and mood stabilizer, but only expand its pharmacological profile. Over the past 10 years, the focus of interest in valproate research has changed due to its ability to alter gene expression both by inhibiting histone deacetylases and by changing levels of DNA methylation. These new studies reveal alternative mechanisms of valproate action rather than trying to test and confirm hypotheses previously put forward.