About: Valproic Acid     Goto   Sponge   NotDistinct   Permalink

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  • Valproic acid, supplied as the sodium salt valproate semisodium or divalproex sodium, is a fatty acid with anticonvulsant properties used in the treatment of epilepsy. The mechanisms of its therapeutic actions are not well understood. It may act by increasing gamma-aminobutyric acid levels in the brain or by altering the properties of voltage dependent sodium channels. Typically supplied in the sodium salt form (CAS number: 76584-70-8). Valproic Acid is also a histone deacetylase inhibitor and is under investigation for treatment of HIV and various cancers. (en)
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http://linked.open...generalReferences
  • # Rosenberg G: The mechanisms of action of valproate in neuropsychiatric disorders: can we see the forest for the trees? Cell Mol Life Sci. 2007 Aug;64(16):2090-103. "Pubmed":http://www.ncbi.nlm.nih.gov/pubmed/17514356 # Lehrman G, Hogue IB, Palmer S, Jennings C, Spina CA, Wiegand A, Landay AL, Coombs RW, Richman DD, Mellors JW, Coffin JM, Bosch RJ, Margolis DM: Depletion of latent HIV-1 infection in vivo: a proof-of-concept study. Lancet. 2005 Aug 13-19;366(9485):549-55. "Pubmed":http://www.ncbi.nlm.nih.gov/pubmed/16099290 # Schwartz C, Palissot V, Aouali N, Wack S, Brons NH, Leners B, Bosseler M, Berchem G: Valproic acid induces non-apoptotic cell death mechanisms in multiple myeloma cell lines. Int J Oncol. 2007 Mar;30(3):573-82. "Pubmed":http://www.ncbi.nlm.nih.gov/pubmed/17273758 # Valentini A, Gravina P, Federici G, Bernardini S: Valproic acid induces apoptosis, p16INK4A upregulation and sensitization to chemotherapy in human melanoma cells. Cancer Biol Ther. 2007 Feb;6(2):185-91. Epub 2007 Feb 5. "Pubmed":http://www.ncbi.nlm.nih.gov/pubmed/17218782 # FDA label (en)
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  • approved (en)
  • investigational (en)
http://linked.open...drugbank/halfLife
  • 9-16 hours (following oral administration of 250 mg to 1000 mg) (en)
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  • For treatment and management of seizure disorders, mania, and prophylactic treatment of migraine headache. In epileptics, valproic acid is used to control absence seizures, tonic-clonic seizures (grand mal), complex partial seizures, and the seizures associated with Lennox-Gastaut syndrome. (en)
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sameAs
Title
  • Valproic Acid (en)
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http://linked.open...mechanismOfAction
  • Valproic Acid dissociates to the valproate ion in the gastrointestinal tract and then binds to and inhibits GABA transaminase. 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. It is also a histone deacetylase inhibitor. 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. (en)
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  • Valproate is metabolized almost entirely by the liver. Less than 3% of an administered dose is excreted unchanged in urine. Mitochondrial ß-oxidation is the other major metabolic pathway, typically accounting for over 40% of the dose. (en)
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  • Depakene (en)
  • Dipropylacetic acid (en)
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