REVIEW Valproic Acid is an anticonvulsant and mood-stabilizing drug used primarily in the treatment of epilepsy and bipolar disorder. It is also used to treat migraine headaches and schizophrenia. In epileptics, valproic acid is used to control absence seizures, grand mal seizures, complex partial seizures, and the seizures associated with Lennox-Gastaut syndrome. Valproic Acid is believed to affect the function of the neurotransmitter GABA (as a GABA transaminase inhibitor) in the human brain. The drug's anticonvulsant activity may be related to increased brain concentrations of gamma aminobutyric acid (GABA), an inhibitory neurotransmitter in the CNS, by inhibiting enzymes that catabolize GABA or block the reuptake of GABA into glia and nerve endings. Valproic Acid may also work by suppressing repetitive neuronal firing through inhibition of voltage-sensitive sodium channels.
Valproic acid has also been shown to be an inhibitor of an enzyme called histone deacetylase 1 (HDAC1). HDAC1 is needed for HIV to remain in infected cells. A study published in August 2005 revealed that patients treated with valproic acid in addition to highly active antiretroviral therapy (HAART) showed a 75% reduction in latent HIV infection.
G Rosenberg, The mechanisms of action of valproate in neuropsychiatric disorders: can we see the forest for the trees? Cell Mol Life Sci. 2007;64(16):2090-2103.
G Lehrman, IB Hogue,S Palmer, C Jennings, CA Spina, A Wiegand, AL Landay, RW Coombs, DD Richman, JW Mellors, JM Coffin, RJ Bosch, DM Margolis: Depletion of latent HIV-1 infection in vivo: a proof-of-concept study. Lancet. 2005 19;366(9485):549-555.
C Schwartz, V Palissot, N Aouali, S Wack, NH Brons, B Leners, M Bosseler, G Berchem Valproic acid induces non-apoptotic cell death mechanisms in multiple myeloma cell lines. Int J Oncol. 2007;30(3):573-82.
A Valentini, P Gravina, G Federici, S Bernardini: Valproic acid induces apoptosis, p16INK4A upregulation and sensitization to chemotherapy in human melanoma cells. Cancer Biol Ther. 2007;6(2):185-91.
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