Carbamazepine is an inhibitor of histone deacetylases.

Article Details

Citation

Copy to clipboard

Beutler AS, Li S, Nicol R, Walsh MJ

Carbamazepine is an inhibitor of histone deacetylases.

Life Sci. 2005 May 13;76(26):3107-15.

PubMed ID

15850602 [ View in PubMed

]

Abstract

Carbamazepine (CBZ) is a common antiepileptic drug (AED) that acts through multiple mechanisms including blockade and potentiation of cation channels and modulation of neurotransmitter levels. Whether it affects any component of the gene transcription machinery is unknown. Histone deacetylases (HDAC) are important in the regulation of gene expression and are currently considered a potential target for drug development. Using a high-throughput screening assay based on acetylation-dependent gene expression, we identified CBZ as a candidate and proceeded to characterize its effects on HDAC. CBZ induced acetylation of histone H4 in the HepG2 liver carcinoma cell line. CBZ inhibited HDAC 3 and HDAC 7, which are representatives of HDAC class I and II respectively. Quantitative testing in an in vitro assay demonstrated HDAC inhibition with an IC50 of 2 microM. The major active metabolite of CBZ, CBZ-10,11-epoxide, was found to have the same HDAC inhibitory activity. The IC50 is considerably lower than therapeutic plasma levels that are typically achieved in patients (25-51 microM). CBZ shares important clinical characteristics (teratogenicity, activity as a mood stabilizer) with valproic acid, another AED that was recently identified as an inhibitor of HDAC. These observations raise the possibility that HDAC inhibition may contribute to the pharmacological profile of CBZ.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Valproic acid	Histone deacetylase 9	Protein	Humans	Yes	Inhibitor	Details