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.