Sugimoto H
Tsukuba Research Laboratories, Eisai Co., Ibaraki, Japan.
Chem Rec. 2001;1(1):63-73. doi: 10.1002/1528-0691(2001)1:1<63::AID-TCR9>3.0.CO;2-J.
The role of the cholinergic system with respect to cognitive deficits characteristic of Alzheimer's disease (AD) has led to a number of studies focusing on the development of acetylcholinesterase (AChE) inhibitors as a drug for treating this disease. The earliest known AChE inhibitors, namely, physostigmine and tacrine, performed poorly in clinical trials (e.g., poor oral activity, brain penetration, and hepatotoxic liability). Studies were then focused on finding a new type of acetylcholinesterase inhibitor that would overcome the disadvantages of these two compounds. Donepezil hydrochloride inaugurates a new class of AChE inhibitors with longer and more selective action and with manageable adverse effects.
胆碱能系统在阿尔茨海默病（AD）特征性认知缺陷方面所起的作用，引发了大量研究，这些研究聚焦于开发乙酰胆碱酯酶（AChE）抑制剂作为治疗该疾病的药物。最早为人所知的AChE抑制剂，即毒扁豆碱和他克林，在临床试验中表现不佳（例如口服活性差、脑渗透性差以及有肝毒性风险）。随后的研究集中在寻找一种新型的乙酰胆碱酯酶抑制剂，以克服这两种化合物的缺点。盐酸多奈哌齐开创了一类新型的AChE抑制剂，其作用时间更长、选择性更高，且不良反应易于控制。
