The Sound of Evolution
Valproate
Mechanism of action:
Valproate has multiple mechanisms of action. Valproate inhibits GABA transaminase, reducing the breakdown of GABA, and enhances the activity of glutamate decarboxylase, increasing the synthesis of GABA and strengthening GABA-mediated effects in the central nervous system. Valproate also inhibits voltage-gated sodium channels, prolongs their inactivated state, and suppresses high-frequency repetitive firing. In thalamic neurons, valproate inhibits T-type calcium channels, thereby reducing pathological thalamocortical rhythmic activity.
Reference(s):
1. Rosenberg G et al. (2007). The mechanisms of action of valproate in neuropsychiatric disorders: can we see the forest for the trees? Cell Mol Life Sci.
2. Lehrman G et al. (2005). Depletion of latent HIV-1 infection in vivo: a proof-of-concept study. Lancet.
3. Schwartz C et al. (2007). Valproic acid induces non-apoptotic cell death mechanisms in multiple myeloma cell lines. Int J Oncol.