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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.
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Hachiro Sugimoto (2001) studied this question.
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