TY - JOUR
T1 - Effect of a M1 allosteric modulator on scopolamine-induced amnesia
AU - Espinosa-Raya, Judith
AU - Espinoza-Fonseca, M.
AU - Picazo, O.
AU - Trujillo-Ferrara, J.
PY - 2007/1
Y1 - 2007/1
N2 - 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.
AB - 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.
KW - Allosteric
KW - Alzheimer's disease
KW - Docking simulations
KW - Memory
KW - Scopolamine
KW - Succinic acid
KW - p-aminophenol
UR - http://www.scopus.com/inward/record.url?scp=33846086127&partnerID=8YFLogxK
U2 - 10.2174/157340607779317526
DO - 10.2174/157340607779317526
M3 - Artículo
SN - 1573-4064
VL - 3
SP - 7
EP - 11
JO - Medicinal Chemistry
JF - Medicinal Chemistry
IS - 1
ER -