Bonifati V, Meco G
Department of Neurosciences, University La Sapienza, Rome, Italy.
Pharmacol Ther. 1999 Jan;81(1):1-36. doi: 10.1016/s0163-7258(98)00032-1.
Levodopa remains the most effective drug for Parkinson's disease (PD). However, its benefits are limited owing to extensive metabolism by catechol-O-methyltransferase (COMT), especially if levodopa is used in combination with peripheral dopa-decarboxylase inhibitors. A new generation of potent, orally active, selective, and reversible COMT inhibitors has become available recently. Among these, tolcapone and entacapone have been best characterised. Preclinical and clinical studies have shown that COMT inhibitors markedly enhance levodopa availability and prolong its plasma half-life. In recent large clinical trials they proved to be able to ameliorate motor fluctuations, reduce disability, and decrease levodopa requirements in PD patients. The tolerability profiles of entacapone and tolcapone are good. COMT inhibition promises to become an important means of extending the benefits of levodopa therapy in PD.
左旋多巴仍然是治疗帕金森病（PD）最有效的药物。然而，由于儿茶酚-O-甲基转移酶（COMT）对其广泛的代谢作用，其疗效受到限制，特别是当左旋多巴与外周多巴脱羧酶抑制剂联合使用时。最近已出现新一代强效、口服活性、选择性和可逆的COMT抑制剂。其中，托卡朋和恩他卡朋的特性已得到最充分的研究。临床前和临床研究表明，COMT抑制剂可显著提高左旋多巴的利用率并延长其血浆半衰期。在最近的大型临床试验中，它们被证明能够改善运动波动、减少残疾并降低PD患者对左旋多巴的需求。恩他卡朋和托卡朋的耐受性良好。抑制COMT有望成为扩大左旋多巴治疗PD益处的重要手段。
