Possible Interaction: Gamma-Aminobutyric Acid and Valproic Acid

“Currently, 2 antiepileptic drugs, valproate (VPA) and vigabatrin, gamma‐vinyl GABA (GVG), are available, which are supposed to inhibit the degradation of GABA.”

“ Valproic acid increases synaptosomal GABA concentrations, thus affecting all types of GABA receptors.”

“ Sodium valproate (SV) inhibits GABA transaminase so increasing the endogenous GABAergic tone.”

“Following treatment with divalproex sodium , plasma GABA levels decreased significantly (p < .05), compared to placebo.”

“Higher pretreatment plasma GABA levels were significantly (p = .04) related to a better clinical response to divalproex (n = 19).”

“Although VPA increases brain gamma-aminobutyric acid (GABA) concentrations, the anticonvulsant effect appears to be more closely associated with a reduction in brain concentrations of aspartic acid (Chapman et al. 1982, 1983; Schechter et al. 1978).”

“The effect of sodium valproate , a drug which has been demonstrated to increase gamma-aminobutyric acid levels in the CNS, on tardive dyskinesia and psychiatric symptoms was investigated in a double-blind cross-over study on 32 chronic psychiatric patients.”

“At maximum dose levels, combined DPA and GABA treatment led to an apparent increase in the central turnover of both dopamine and serotonin, as estimated by the oral probenecid-loading test.”

“ Sodium valproate interacts with biological systems through different mechanisms such as activation of gamma-aminobutyric acid (GABA)-sensitive chloride channels and inhibition of histone deacetylase.”

“Focused studies uncovered the potential of valproic acid to interfere with multiple regulatory mechanisms including histone deacetylases, GSK3 alpha and beta, Akt, the ERK pathway, the phosphoinositol pathway, the tricarboxylic acid cycle, GABA , and the OXPHOS system.”

“The inhibitory action of DPA on GABA degradation, resulting in an enhanced release of GABA , is probably responsible for this behavioral effect, since GABA antagonists, like bicuculline and picrotoxin, have been shown to suppress this behavior.”