Valproic acid is an analog of the natural fatty acid valeric acid that inhibits class I histone deacetylases (HDACs) with an IC50 value of approximately 2 mM. It decreases the number of axon branches in sensory neurons isolated from newborn rat dorsal root ganglia, an effect that is reversed by inositol-1,4,5-trisphosphate (1,4,5-IP3). In vivo, valproic acid inhibits amyloid-β deposition and neuritic plaque formation and decreases escape latency in Morris water maze, indicating improved memory performance, in the APP23 transgenic mouse model of Alzheimer's disease. Valproic acid has anticonvulsant activity in the pentylenetetrazol seizure threshold test in mice (ED50 = 0.71 mmol/kg) but induces neurotoxicity when administered at doses greater than or equal to 1.2 mmol/kg. Formulations containing valproic acid have been used in the treatment of bipolar disorder and various seizure disorders.
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