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Donepezil Hydrochloride (E2020) and Other Acetylcholinesterase Inhibitors

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A wide range of evidence shows that acetylcholinesterase (AChE) inhibitors can interfere with the progression of Alzheimer disease (AD). The successful development of these compounds was based on a well-accepted theory that the decline in cognitive and mental functions associated with AD is related to the loss of cortical cholinergic neurotransmission. The earliest known AChE inhibitors, namely, physostigmine and tacrine, showed modest improvement in the cognitive function of Alzheimers patients. However, clinical studies show that physostigmine has poor oral activity, brain penetration and pharmacokinetic parameters while tacrine has 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 with manageable adverse effects. Currently, there are about 19 new Alzheimers drugs in various phases of clinical development.
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Keywords: ACh releasers; AChE inhibitors; Brain acetylcholine concentrations; BuChE; M1 M3 Receptor agonists; TAK 147; acetylcholinesterase inhibitors; alzheimer s disease; alzheimer s disease treatment; amiridine; anti AChE Activity; anti amyloid; anti inflammatory agents; anti oxidants; cholineric enhancement therapy; cortical cholinergic neurotransmission; crystal structure; donepezil hydrochloride; donepezil hydrocloride; eptastigmine; estrogen replacement therapy; galanin receptor antagonist; galanthamine; hepatotxic liability; huperzine A; metrifonate; molecular modeling; n alkyl analogs; nicotinic agonists; physostigmine; receptor dependent docking; rivastigmine; velnacrine

Document Type: Review Article

Publication date: 2000-03-01

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  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.
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