The Impact of Catechol-O-Methyltransferase Inhibition in Modern Treatment of Parkinson's Disease

作者：Salmen S^*; Mueller T; Muhlack S M

来源：Aktuelle Neurologie, 2011, 38(5): 253-260.

DOI：10.1055/s-0031-1285870

• levodopa
• COMT inhibition
• metabolism
• Parkinson therapy
• motor complications

Levodopa (LD) is the oldest, most efficacious and best-tolerated drug for dopaminergic substitution of patients with Parkinson's disease (PD). Its main drawback is its short half-life, which supports the onset of motor complications in the longterm. Therefore therapy is started as late as possible. The at first expected delay of the onset of motor complications under the combination of LD with carbidopa (CD) and the catechol-O-methyltransferase (COMT) inhibitor entacapone (EN) on the basis of pharmacokinetic trials and experimental research to a certain extent, was proved to be wrong in the STRIDE-PD study. Although the control of symptoms and consecutive improved quality of life were better, motor complications under COMT inhibition occurred even earlier. Small studies show a possible influence on cognition and muscle strength, but further research is necessary. There is also an evidence for a reduction in homocysteine synthesis under the combination of COMT inhibition and LD administration. Besides, the triple combination of LD/CD/EN the COMT inhibitors EN and tolcapone (TO) is available for therapy. The safety data of EN compared with TO explain the current preference of EN, even if TO probably offers a better efficacy. The indication for additional COMT inhibition still remains in the treatment of motor complications like "wearing off" and other fluctuations as yet. New therapeutic approaches due to a better understanding of the enzyme and its features are still to be awaited.

• 出版日期2011-6