Effect of a M1 allosteric modulator on scopolamine-induced amnesia

Judith Espinosa-Raya, M. Espinoza-Fonseca, O. Picazo, J. Trujillo-Ferrara

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

It is well accepted that acetylcholine is involved in memory and learning processes and that loss of memory is characteristic of Alzheimer's 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 least the succinamide of p-aminophenol could represent a novel candidate for the treatment of AD.

Original languageEnglish (US)
Pages (from-to)7-11
Number of pages5
JournalMedicinal chemistry
Volume3
Issue number1
DOIs
StatePublished - Jan 1 2007

Keywords

  • Allosteric
  • Alzheimer's disease
  • Docking simulations
  • Memory
  • Scopolamine
  • Succinic acid
  • p-aminophenol

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    Espinosa-Raya, J., Espinoza-Fonseca, M., Picazo, O., & Trujillo-Ferrara, J. (2007). Effect of a M1 allosteric modulator on scopolamine-induced amnesia. Medicinal chemistry, 3(1), 7-11. https://doi.org/10.2174/157340607779317526