Abstract
At present the only FDA-approved therapy for Alzheimers disease involves the administration of acetylcholinesterase inhibitors, to alleviate the cholinergic deficit associated with this disease. However, none of the approved drugs is ideal in efficacy or tolerability. One possible strategy to improve selectivity and potency is to design drugs that can simultaneously bind to the catalytic and peripheral anionic sites of AChE. In this review we will describe the development of dimeric AChE inhibitors, from the early observations of high inhibition potency by bis-quaternary inhibitors, to the structure-based design of dimers based on tacrine, huperzine A, galanthamine, and polyamines.
Keywords: acetylcholinesterase, butyrylcholinesterase, alzheimers disease, inhibitor, bivalent, dimer
Current Pharmaceutical Design
Title: Development of Bivalent Acetylcholinesterase Inhibitors as Potential Therapeutic Drugs for Alzheimers Disease
Volume: 10 Issue: 25
Author(s): Da-Ming Du and Paul R. Carlier
Affiliation:
Keywords: acetylcholinesterase, butyrylcholinesterase, alzheimers disease, inhibitor, bivalent, dimer
Abstract: At present the only FDA-approved therapy for Alzheimers disease involves the administration of acetylcholinesterase inhibitors, to alleviate the cholinergic deficit associated with this disease. However, none of the approved drugs is ideal in efficacy or tolerability. One possible strategy to improve selectivity and potency is to design drugs that can simultaneously bind to the catalytic and peripheral anionic sites of AChE. In this review we will describe the development of dimeric AChE inhibitors, from the early observations of high inhibition potency by bis-quaternary inhibitors, to the structure-based design of dimers based on tacrine, huperzine A, galanthamine, and polyamines.
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Cite this article as:
Du Da-Ming and Carlier R. Paul, Development of Bivalent Acetylcholinesterase Inhibitors as Potential Therapeutic Drugs for Alzheimers Disease, Current Pharmaceutical Design 2004; 10 (25) . https://dx.doi.org/10.2174/1381612043383412
DOI https://dx.doi.org/10.2174/1381612043383412 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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