Creation and Study of the Mechanism of Action of Compounds of a New Class of Positive Modulators of AMPA Receptors – Derivatives of 3,7-Diazabicyclo[3.3.1]nonanes

V. V. Grigoriev; Григорьев В. В.; M. I. Lavrov; Лавров М. И.; V. A. Palyulin; Палюлин В. А.; T. L. Garibova; Гарибова Т. Л.; K. V. Anokhin; Анохин К. В.; S. O. Bachurin; Бачурин С. О.

doi:10.31857/S1027813323020073

Creation and Study of the Mechanism of Action of Compounds of a New Class of Positive Modulators of AMPA Receptors – Derivatives of 3,7-Diazabicyclo[3.3.1]nonanes

Authors: Grigoriev V.V.¹, Lavrov M.I.², Palyulin V.A.², Garibova T.L.³, Anokhin K.V.⁴, Bachurin S.O.¹
Affiliations:
1. Institute of Physiologically Active Compounds at Federal Research Center of Problems of Chemical Physics and Medicinal Chemistry, Russian Academy of Sciences
2. Department of Chemistry, Lomonosov Moscow State University
3. Federal State Budgetary Scientific Institute “Scientific Research Institute of Pharmacology named after V.V. Zakusova
4. Federal State Budgetary Scientific Institute “Scientific Research Institute of Normal Physiology named after P.K. Anokhin”
Issue: Vol 40, No 2 (2023)
Pages: 108-120
Section: Review Articles
URL: https://journal-vniispk.ru/1027-8133/article/view/142200
DOI: https://doi.org/10.31857/S1027813323020073
EDN: https://elibrary.ru/UCLORH
ID: 142200

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Abstract

The review presents the results of consistent scientific studies of a new class of positive allosteric modulators of AMPA receptors from the class of 3,7-diazabicyclo[3.3.1]nonane derivatives, starting from the theoretical prediction of the structures of compounds, their synthesis, and studying their effect on the currents of AMPA receptors as evidence of assignment them to the PAM class, studying their activity and effectiveness in behavioral experiments simulating both various acute impairments of memory and cognitive functions, and in chronic experiments simulating the pathology of Alzheimer’s disease, studying their molecular mechanism of interaction with the AMPA receptor using 3D computer modeling, radioligand studies of labeled compound 5 with fractions of synaptic membranes of the brain hippocampus in order to determine the “seats” of this PAM in the brain of rats. All of the above characterizes new compounds of this class as the most active among known PAMs in the world, having a pronounced cognitive-stimulating effect both in normal animals and in various models of pathological memory disorder, which indicates their great therapeutic potential.

Keywords

AMPA receptors, positive allosteric modulators, cognitive stimulating effect, radioligand binding

References

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