[HTML][HTML] Histone deacetylase is a direct target of valproic acid, a potent anticonvulsant, mood stabilizer, and teratogen

CJ Phiel, F Zhang, EY Huang, MG Guenther… - Journal of Biological …, 2001 - ASBMB
Valproic acid is widely used to treat epilepsy and bipolar disorder and is also a potent
teratogen, but its mechanisms of action in any of these settings are unknown. We report that
valproic acid activates Wntdependent gene expression, similar to lithium, the mainstay of
therapy for bipolar disorder. Valproic acid, however, acts through a distinct pathway that
involves direct inhibition of histone deacetylase (IC 50 for HDAC1= 0.4 mm). At therapeutic
levels, valproic acid mimics the histone deacetylase inhibitor trichostatin A, causing …