Biochemistry and pharmacology of catechol-O-methyltransferase inhibitors

Abstract

Catechol-O-methyltransferase (COMT) is an important enzyme in the metabolism of catechol structured compounds such as catecholamines, catecholestrogens, and L-dopa. When combined with decarboxylase inhibitor L-dopa is the most efficacious treatment for Parkinson's disease. Bioavailability and efficacy of L-dopa treatment can be enhanced greatly by the use of COMT inhibitors. This has been the driving force for development of new selective and potent COMT inhibitors. The success in COMT inhibitor development has generated a tremendous scientific interest in the role of COMT in health and disease. COMT inhibitors have also helped to clarify the reaction mechanism of COMT, increased interest in its structural biology, and physicochemical properties in order to develop even better COMT inhibitors. New techniques, especially the transgenic mice, have revealed further new aspects about the role of COMT in periphery as well as in the brain.