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Current Pharmaceutical Design

Editor-in-Chief

ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

An Overview of the Current and Novel Drugs for Alzheimers Disease with Particular Reference to Anti-Cholinesterase Compounds

Author(s): Marcela Colombres, Juan Paulo Sagal and Nibaldo C. Inestrosa

Volume 10, Issue 25, 2004

Page: [3121 - 3130] Pages: 10

DOI: 10.2174/1381612043383359

Price: $65

Abstract

Several cellular processes could be targeted if the complex nature of Alzheimers disease (AD) was already understood. Most of AD treatments have been focused on the inhibition of acetylcholinesterase (AChE) in order to raise the levels of its substrate, i.e. the neurotransmitter acetylcholine (ACh), to augment cognitive functions of affected patients. Effectiveness in AChE inhibition and side-effect issues of clinical (tacrine, donepezil, galanthamine and rivastigmine) as well as of novel inhibitors is reviewed here. Novel design methods for the inhibition of AChE include the use of in silico tools to predict the interactions between AChE and the desired compound, both at the active site of the enzyme, responsible of hydrolysing ACh and with the peripheral anionic site (PAS), which has been described as a promoting agent of the amyloid β-peptide (Aβ) aggregation present in the senile plaques of the brain of AD individuals.

Keywords: alzheimers disease, ache, cholinesterase inhibitors


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