Introductory Remarks: Catechol-O-Methyltransferase Inhibition—An Innovative Approach To Enhance l-Dopa Therapy In Parkinson'S Disease With Dual Enzyme Inhibition

Catechol- O -methyltransferase (COMT) enzyme and its inhibition have been closely related to the treatment of Parkinson’s disease (PD) patients with motor fluctuations needing enhancement of their levodopa ( l -dopa) therapy ( l -dopa/dopa decarboxylase inhibitor), this indication being so far the only clinical application of COMT inhibitors. l -dopa treatment has remained the most effective therapy for PD, but its further development has been quite a challenge mainly due to the effective metabolism of l -dopa in the human body by multiple pathways, decarboxylation and O-methylation being the two most important of them. The introduction of clinically effective and safe COMT inhibitors has greatly increased the usefulness of l -dopa therapy, but how to utilize the full potential of l -dopa is still unsolved leaving a need for more potent COMT inhibitors.