Effect of a M1 allosteric modulator on scopolamine-induced amnesia.
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 at least the succinamide of p-aminophenol could represent a novel candidate for the treatment of AD.
Espinosa-Raya
J
J
Escuela Superior de Medicina, Instituto Politécnico Nacional, Sección de Estudios de Posgrado e Investigación y Departamento de Bioquímica, Plan de San Luis y Díaz Mirón, México, DF, 11340 México. judith.espinosa@terra.com.mx
Espinoza-Fonseca
M
M
Picazo
O
O
Trujillo-Ferrara
J
J
D000647:Amnesia / Q000139:chemically induced*; D000818:Animals; D001665:Binding Sites; D018678:Cholinergic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D003214:Conditioning, Classical / Q000187:drug effects; D015195:Drug Design; D005702:Galantamine / Q000494:pharmacology; D008297:Male; D008568:Memory / Q000187:drug effects; D008958:Models, Molecular; D018727:Muscarinic Antagonists; D051381:Rats; D017208:Rats, Wistar; D043643:Receptor, Muscarinic M1 / Q000187:drug effects*; D012601:Scopolamine
D018678:Cholinergic Agents; D018727:Muscarinic Antagonists; D043643:Receptor, Muscarinic M1; D005702:Galantamine; D012601:Scopolamine