CNS & Neurological Disorders - Drug Targets

(Formerly Current Drug Targets - CNS & Neurological Disorders)

Stephen D. Skaper  
Department of Pharmaceutical and Pharmacological Sciences
University of Padova


Inhibitors of Catechol-O-Methyltransferase

Author(s): James C. Barrow

Affiliation: Lieber Institute for Brain Development, 336 John G. Rangos Building, 855 North Wolfe St., Baltimore, MD 21205, USA.


Since the identification of Catechol-O-Methyltransferase (COMT) by Axelrod in 1957, many inhibitors of this enzyme have been reported. While COMT inhibition may be beneficial in a number of disease states, most of the effort over the years has been directed at boosting L-DOPA concentrations as adjunct treatment for Parkinson’s disease. This review summarizes the major classes of COMT inhibitors, from early catechol and pyrogallol variants to bisubstrate inhibitors. The nitrocatechol substructure has proven to be a particularly productive scaffold, resulting in two marketed drugs and several improved drug candidates working their way through clinical trials.

Keywords: Catechol-O-methyltransferase, COMT, dopamine, L-DOPA, Parkinson's disease, nitrocatechol, MB-COMT, SAM Binding, HPLC, DOPAC

Order Reprints Order Eprints Rights & PermissionsPrintExport

Article Details

Page: [324 - 332]
Pages: 9
DOI: 10.2174/187152712800672517