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Does valproic acid affect tumor growth and improve survival in glioblastomas?


Valproic acid (VPA) is an anticonvulsant drug with established activity in controlling seizures in glioma patients [1–2]. The mechanisms of the antiepileptic activity of VPA are well known [3]: enhancement of the inhibitory effects of the neurotransmitter GABA, blockage of the voltage-gated sodium channels and T-type calcium channels, attenuation of NMDA-mediated excitation and alteration of firing frequency of neurons. VPA is extensively bound to plasma proteins (>90%), mainly to plasma albumin, and the extent of binding decreases with increasing drug concentrations. VPA easily penetrates the blood–brain barrier: mechanisms involve both passive diffusion and bidirectional carrier-mediated transport via an anion exchanger at the brain capillary endothelium. Cerebrospinal fluid (CSF) concentrations vary between 1 and 10% of total plasma concentrations. Active transport mediates the uptake of VPA into neuronal and glial cells, which results in intracellular concentrations that are higher than interstitial fluid concentrations.

Click here to view the full article in our partner journal CNS Oncology.