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Inhibitors of Catechol-O-Methyltransferase

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

Document Type: Research Article

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

Publication date: 2012-05-01

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  • CNS & Neurological Disorders - Drug Targets aims to cover all the latest and outstanding developments on the medicinal chemistry, pharmacology, molecular biology, genomics and biochemistry of contemporary molecular targets involved in neurological and central nervous system (CNS) disorders e.g. disease specific proteins, receptors, enzymes, genes. Each issue of the journal will contain a series of timely in-depth reviews written by leaders in the field covering a range of current topics on drug targets involved in neurological and CNS disorders. As the discovery, identification, characterization and validation of novel human drug targets for neurological and CNS drug discovery continues to grow; this journal will be essential reading for all pharmaceutical scientists involved in drug discovery and development.
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