Abstract
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
CNS & Neurological Disorders - Drug Targets
Title:Inhibitors of Catechol-O-Methyltransferase
Volume: 11 Issue: 3
Author(s): James C. Barrow
Affiliation:
Keywords: Catechol-O-methyltransferase, COMT, dopamine, L-DOPA, Parkinson's disease, nitrocatechol, MB-COMT, SAM Binding, HPLC, DOPAC
Abstract: 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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Cite this article as:
C. Barrow James, Inhibitors of Catechol-O-Methyltransferase, CNS & Neurological Disorders - Drug Targets 2012; 11 (3) . https://dx.doi.org/10.2174/187152712800672517
DOI https://dx.doi.org/10.2174/187152712800672517 |
Print ISSN 1871-5273 |
Publisher Name Bentham Science Publisher |
Online ISSN 1996-3181 |
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