Department of Neurology, University of Helsinki, Helsinki, Finland.
Int Rev Neurobiol. 2010;95:207-25. doi: 10.1016/B978-0-12-381326-8.00009-0.
Entacapone and tolcapone are reversible COMT inhibitors which have been approved for clinical use in patients with Parkinson disease (PD). Nebicapone is a third COMT inhibitor which has been studied in humans. COMT inhibitors are used in combination with levodopa and a dopa decarboxylase (DDC) inhibitor. Each of them has problems either in pharmacokinetics, pharmacodynamics, clinical efficacy, or in safety. All three inhibitors have short elimination half-lives, about 2-3h. Tolcapone is longer acting and more potent COMT inhibitor than entacapone; nebicapone lies in between. However, none of the present inhibitors cause a complete peripheral COMT inhibition. Tolcapone and nebicapone have increased more levodopa AUC than entacapone which is reflected also in their clinical efficacy. The most common adverse event with COMT inhibitors is dyskinesia which is usually managed by decreasing levodopa dose. The greatest problem with tolcapone and probably also with nebicapone is their liver toxicity which is not seen with entacapone. Tolcapone causes severe diarrhea more often than entacapone. Though the present COMT inhibitors have improved significantly the treatment of advanced PD patients, they still have several problems and weaknesses leaving room for developing better COMT inhibitors.
恩他卡朋、托卡朋是两种已被批准用于治疗帕金森病（PD）患者的可逆型儿茶酚-O-甲基转移酶（COMT）抑制剂。尼比卡朋是另一种已在人体中进行研究的 COMT 抑制剂。COMT 抑制剂与左旋多巴和多巴胺脱羧酶（DDC）抑制剂联合使用。它们中的每一种在药代动力学、药效学、临床疗效或安全性方面都存在问题。这三种抑制剂的消除半衰期都较短，约为 2-3 小时。托卡朋是一种比恩他卡朋作用时间更长、效力更强的 COMT 抑制剂；尼比卡朋则介于两者之间。然而，目前没有任何一种抑制剂能完全抑制外周 COMT。托卡朋和尼比卡朋增加了左旋多巴 AUC 比恩他卡朋更多，这也反映在它们的临床疗效上。COMT 抑制剂最常见的不良反应是运动障碍，通常通过减少左旋多巴剂量来控制。托卡朋和可能还有尼比卡朋的最大问题是它们的肝毒性，而恩他卡朋则没有这种毒性。托卡朋比恩他卡朋更常引起严重腹泻。尽管目前的 COMT 抑制剂显著改善了晚期 PD 患者的治疗效果，但它们仍存在一些问题和弱点，为开发更好的 COMT 抑制剂提供了空间。
