Reviewing the role of donepezil in the treatment of Alzheimer's disease.
Reviewing the role of donepezil in the treatment of Alzheimer's disease.
复制标题
回顾多奈哌齐在治疗阿尔茨海默病中的作用。
作者：
R. Doody;J. Cummings;M. Farlow
多奈哌齐是一种可逆的、非竞争性的哌啶型乙酰胆碱酯酶抑制剂（AChEI），与目前可用的其他AChEI相比，其结构独特。它被开发为一种对症治疗，以补偿神经元之间胆碱能信号的进行性丢失，这是阿尔茨海默病（AD）患者大脑中神经元细胞丢失的结果。自该药首次获得许可并可用于轻度至中度AD患者（1997年）以来，在15年内进行的临床试验表明，多奈哌齐在AD的所有阶段（从轻度或中度损害患者到重度疾病患者）均有效且耐受良好。已发表的文献包含近2000篇关于多奈哌齐的论文，其中200多篇与随机对照临床试验有关。在轻度认知障碍（MCI）患者中进行的试验未能达到其所有主要目标，但提供了对患者选择和试验设计的见解。总体而言，十多年的多奈哌齐研究逐渐改变了对AD治疗的态度，从普遍认为不存在临床上有用的治疗方法，到今天理解对症治疗可能在痴呆阶段的各个方面都有效。
Donepezil is a reversible, non-competitive piperidine-type acetylcholinesterase inhibitor (AChEI) that is structurally unique compared with other currently available AChEIs. It was developed as a symptomatic treatment to compensate for the progressive loss of cholinergic signal between neurons, a consequence of neuronal cell loss in the brains of patients with Alzheimer's disease (AD). Clinical trials conducted over the 15 years since the drug was first licensed and available for use in patients with mild to moderate AD (1997) have shown that donepezil is efficacious and well tolerated at all stages of AD, from patients with mild or moderate impairment to those with severe disease. The published literature contains nearly 2000 papers on donepezil, and more than 200 of these articles relate to randomized controlled clinical trials. Trials in patients with mild cognitive impairment (MCI) failed to meet all of their primary objectives, but provided insights into patient selection and the design of trials. Overall, more than a decade of donepezil research has gradually changed attitudes toward therapy of AD from a general belief that no clinically useful treatment exists to the present day understanding that symptomatic therapy may be effective across the spectrum of dementia stages.