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
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