Bonifácio Maria João, Palma P Nuno, Almeida Luís, Soares-da-Silva Patrício
Department of Research and Development, BIAL (Portela & Co S.A.), S Mamede do Coronado, Portugal.
CNS Drug Rev. 2007 Fall;13(3):352-79. doi: 10.1111/j.1527-3458.2007.00020.x.
Parkinson's disease (PD) is a neurological disorder characterized by the degeneration of dopaminergic neurons, with consequent reduction in striatal dopamine levels leading to characteristic motor symptoms. The most effective treatment for this disease continues to be the dopamine replacement therapy with levodopa together with an inhibitor of aromatic amino acid decarboxylase (AADC). The efficacy of this therapy, however, decreases with time and most patients develop fluctuating responses and dyskinesias. The last decade showed that the use of catechol-O-methyltransferase inhibitors as adjuvants to the levodopa/AADC inhibitor therapy, significantly improves the clinical benefits of this therapy. The purpose of this article is to review the current knowledge on the enzyme catechol-O-methyltransferase (COMT) and the role of COMT inhibitors in PD as a new therapeutic approach to PD involving conversion of levodopa to dopamine at the target region in the brain and facilitation of the continuous action of this amine at the receptor sites. A historical overview of the discovery and development of COMT inhibitors is presented with a special emphasis on nebicapone, presently under clinical development, as well as entacapone and tolcapone, which are already approved as adjuncts in the therapy of PD. This article reviews human pharmacokinetic and pharmacodynamic properties of these drugs as well as their clinical efficacy and safety.
帕金森病（PD）是一种神经退行性疾病，其特征为多巴胺能神经元变性，导致纹状体多巴胺水平降低，进而引发典型的运动症状。目前治疗该疾病最有效的方法仍然是左旋多巴联合芳香族氨基酸脱羧酶（AADC）抑制剂进行多巴胺替代疗法。然而，这种疗法的疗效会随着时间推移而降低，大多数患者会出现疗效波动和异动症。过去十年的研究表明，使用儿茶酚-O-甲基转移酶抑制剂作为左旋多巴/AADC抑制剂疗法的辅助药物，可显著提高该疗法的临床疗效。本文旨在综述目前关于儿茶酚-O-甲基转移酶（COMT）的知识，以及COMT抑制剂在帕金森病治疗中的作用，这是一种治疗帕金森病的新方法，涉及在脑内靶区域将左旋多巴转化为多巴胺，并促进该胺类物质在受体部位的持续作用。本文将对COMT抑制剂的发现和发展进行历史回顾，特别强调目前正在进行临床开发的奈比卡朋，以及已被批准作为帕金森病治疗辅助药物的恩他卡朋和托卡朋。本文还将综述这些药物的人体药代动力学和药效学特性，以及它们的临床疗效和安全性。
