Orion Pharma, Research Center, Espoo, Finland.
Int Rev Neurobiol. 2010;95:73-118. doi: 10.1016/B978-0-12-381326-8.00005-3.
Catechol-O-methyltransferase (COMT) is an important enzyme in the metabolism of catechol structured compounds such as catecholamines, catecholestrogens, and L-dopa. When combined with decarboxylase inhibitor L-dopa is the most efficacious treatment for Parkinson's disease. Bioavailability and efficacy of L-dopa treatment can be enhanced greatly by the use of COMT inhibitors. This has been the driving force for development of new selective and potent COMT inhibitors. The success in COMT inhibitor development has generated a tremendous scientific interest in the role of COMT in health and disease. COMT inhibitors have also helped to clarify the reaction mechanism of COMT, increased interest in its structural biology, and physicochemical properties in order to develop even better COMT inhibitors. New techniques, especially the transgenic mice, have revealed further new aspects about the role of COMT in periphery as well as in the brain.
儿茶酚-O-甲基转移酶（COMT）是儿茶酚结构化合物如儿茶酚胺、儿茶酚雌激素和左旋多巴代谢中的重要酶。当与脱羧酶抑制剂左旋多巴结合时，它是治疗帕金森病最有效的方法。使用 COMT 抑制剂可以大大提高左旋多巴治疗的生物利用度和疗效。这一直是开发新型选择性和有效 COMT 抑制剂的动力。COMT 抑制剂的成功开发极大地激发了人们对 COMT 在健康和疾病中的作用的科学兴趣。COMT 抑制剂也有助于阐明 COMT 的反应机制，增加了对其结构生物学和物理化学性质的兴趣，以便开发出更好的 COMT 抑制剂。新技术，特别是转基因小鼠，进一步揭示了 COMT 在中枢神经系统和外周组织中的作用的新方面。
