The 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

• Published in: Neurochemical journal 2023-06, Vol.17 (2), p.169-179
• Main Authors: Grigor’ev, V. V., Lavrov, M. I., Palyulin, V. A., Garibova, T. L., Anokhin, K. V., Bachurin, S. O.
• Format: Article
• Language: English
• Subjects: Biomedical and Life Sciences; Biomedicine; Neurosciences; Review Articles
• ISSN: 1819-7124; 1819-7132
• DOI: 10.1134/S1819712423020071

—This 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 the compounds, their synthesis, and study of their effect on the currents of AMPA receptors as evidence of assigning them to the PAM class by studying their activity and effectiveness in behavioral experiments that simulate both various acute impairments of memory and cognitive functions and in chronic experiments that simulate the pathology of Alzheimer’s disease, and by 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 hippocampus in order to determine the binding sites 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 that have a pronounced cognitive-stimulating effect in both normal animals and in various models of pathological memory disorder, which indicates their great therapeutic potential.