Abstract
It is well accepted that acetylcholine is involved in memory and learning processes and that loss of memory is characteristic of Alzheimers disease (AD). Several muscarinic agonists have been shown to be clinically effective in the treatment of AD. However, their use has been limited due to adverse side effects. As a result, more selective M1 agonists are expected to be the next generation of agents for the treatment of AD. One pharmacological approach to evaluate possible cognitive effects of compounds includes their ability to reverse scopolamine-induced amnesia. In the current study the succinamide and succinimide of p-aminophenol, two newly synthesized compounds that were previously designed to be acetylcholine analogues, were evaluated in a Pavlovian/Instrumental autoshaped memory task. Simultaneously, docking studies on the M1 receptor were done. The scopolamine-induced amnesia was reversed by the amide but not the imide. These findings are in line with results derived from the docking simulations, and suggest that at least the succinamide of p-aminophenol could represent a novel candidate for the treatment of AD.
Keywords: Succinic acid, p-aminophenol, scopolamine, allosteric, docking simulations, Alzheimer's disease, memory
Medicinal Chemistry
Title: Effect of a M1 Allosteric Modulator on Scopolamine-Induced Amnesia
Volume: 3 Issue: 1
Author(s): J. Espinosa-Raya, M. Espinoza-Fonseca, O. Picazo and J. Trujillo-Ferrara
Affiliation:
Keywords: Succinic acid, p-aminophenol, scopolamine, allosteric, docking simulations, Alzheimer's disease, memory
Abstract: It is well accepted that acetylcholine is involved in memory and learning processes and that loss of memory is characteristic of Alzheimers disease (AD). Several muscarinic agonists have been shown to be clinically effective in the treatment of AD. However, their use has been limited due to adverse side effects. As a result, more selective M1 agonists are expected to be the next generation of agents for the treatment of AD. One pharmacological approach to evaluate possible cognitive effects of compounds includes their ability to reverse scopolamine-induced amnesia. In the current study the succinamide and succinimide of p-aminophenol, two newly synthesized compounds that were previously designed to be acetylcholine analogues, were evaluated in a Pavlovian/Instrumental autoshaped memory task. Simultaneously, docking studies on the M1 receptor were done. The scopolamine-induced amnesia was reversed by the amide but not the imide. These findings are in line with results derived from the docking simulations, and suggest that at least the succinamide of p-aminophenol could represent a novel candidate for the treatment of AD.
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Cite this article as:
Espinosa-Raya J., Espinoza-Fonseca M., Picazo O. and Trujillo-Ferrara J., Effect of a M1 Allosteric Modulator on Scopolamine-Induced Amnesia, Medicinal Chemistry 2007; 3 (1) . https://dx.doi.org/10.2174/157340607779317526
DOI https://dx.doi.org/10.2174/157340607779317526 |
Print ISSN 1573-4064 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6638 |
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