ABSTRACT
Catechol O-methyltransferase (COMT) plays an important role in the catabolic inactivation of catecholamines. The development of potent and selective inhibitors has provided effective pharmacological tools to investigate the physiological role of the enzyme. The main clinical interest has been the possible application of COMT inhibitors as adjuncts in the L-dopa therapy of Parkinson's disease. COMT, was originally detected in rat liver extracts. Since then, COMT has been found in many species: animals, plants, and procaryotes. The COMT enzyme catalyzes the transfer of the methyl group from the coenzyme S-adenosyl-L-methionine to one of the phenolic hydroxyl groups of a catechol or substituted catechol. The drug-design process of COMT inhibitors started long before the structure of the target molecule was available. After inhibition of dopa decarboxylase, COMT is responsible for the main catabolism of L-dopa. In the central nervous system COMT together with monoamino oxidase participitates in the metabolism of L-dopa and dopamine.
