Catechol O-methyltransferase (COMT) inhibitors are valuable co-adjuvant drugs in the clinical management of Parkinson’s disease (PD), and recent data also suggest therapeutic benefits in other neurological disorders associated with dopamine depletion. However, the relationship between tolcapone administration with fatal cases of drug-induced liver damage gave COMT inhibitors a bad reputation as hepatotoxic drugs. Thus, there is a pressing need to feed the pipeline with safe COMT inhibitors to replace tolcapone, the only currently available COMT inhibitor that effectively reaches the brain. Recent efforts led to promising phenolic and nonphenolic COMT inhibitors, which allow isoform-specific targeting and avoid the toxicological and pharmacokinetic (PK) shortcomings of classic nitrocatechols. Here, we describe advances made in this field over the past 5 years.

儿茶酚Oα-甲基转移酶 (COMT) 抑制剂是帕金森病 (PD) 临床管理中有价值的辅助药物，最近的数据还表明在与多巴胺耗竭相关的其他神经系统疾病中具有治疗益处。然而，托卡朋给药与药物性肝损伤致死病例之间的关系使 COMT 抑制剂作为肝毒性药物而名声不佳。因此，迫切需要用安全的 COMT 抑制剂来替代 tolcapone，这是目前唯一可以有效到达大脑的 COMT 抑制剂。最近的努力导致了有前途的酚类和非酚类 COMT 抑制剂，它们允许异构体特异性靶向并避免经典硝酸邻苯二酚的毒理学和药代动力学 (PK) 缺点。这里，