Valproic acid is an anticonvulsant drug that was first synthesized in 1882 and thought to have no biological activity. In 1962, Pierre Eymard discovered its anticonvulsant properties by accident when he used it as a carrier for other anticonvulsant drugs in a trial on rats. Today, valproic acid is on the World Health Organization list of essential medicines and a common treatment for epilepsy.
Valproic acid also has FDA approval for the treatment of bipolar disorder. Its mechanism of action is not fully understood. It may work by increasing levels of GABA in the brain or by inhibiting histone deacetylase and thereby altering brain gene expression. In 2018, Joshi et al. hypothesized that valproic acid and the mood stabilizer lithium alter the expression levels of synapsin, proteins expressed in neurons that regulate synapse function, including vesicle maintenance and neurotransmitter release.
The researchers dosed rats with lithium, valproic acid, or saline twice daily for two weeks. RNA was then extracted from the brain tissue of the rats, and real-time PCR was used to measure the synapsin expression level. Rats dosed with lithium or valproic acid showed increases in synapsin expression across several brain tissues. Specifically, synapsin IIa increased by about 25% in the hippocampus and prefrontal cortex, and synapsin IIb increased by 25-50% in the hippocampus and striatum. Both lithium- and valproic-acid-dosed rats saw these increases.
Valproic acid may work to treat epilepsy and bipolar disorder through the upregulation of synapsins. LKT Laboratories carries valproic acid as well as a number of anticonvulsant and antiepileptic molecules for research use.
Joshi H, Sharma R, Prashar S, Ho J, Thomson S, Mishra R. Differential Expression of Synapsin I and II upon Treatment by Lithium and Valproic Acid in Various Brain Regions. International Journal of Neuropsychopharmacology (2018) 21(6): 616–622.