Palagina N. Search for new nootropic drugs among 4-aminobutanoic acid derivatives and study of their pharmacodynamics

The thesis of Palagina N.Yu. presents the results of studying the antiamnestic activity of 11 derivatives of 4-aminobutanoic acid and the study of 4-(benzyl(methyl)amino) butanoic acid, which was selected as the leading compound for antiamnestic and antihypoxic activity among these derivatives according to the results of pharmacological screening, its effectiveness in experimental models of acute cerebral circulatory disorders (ACCD) and closed traumatic brain injury (CTBI) in rats and certain pharmacological properties: effects on memory phases, anxiety, depression, skeletal muscle tone and coordination of animal movements, as well as the study of acute toxicity. According to the results of pharmacological screening of 11 new derivatives of 4-aminobutanoic acid for the presence of antiamnestic activity, 4 compounds were found that showed probable activity. Among the most active compounds, two were selected: KGM-2 (4- (di (hydroxymethyl) amino) butanoic acid), KGM-5 (4- (benzyl (methyl) amino) butanoic acid), for which a dose-dependent antiamnestic effect has been proven. Analysis of the structure-antiamnestic activity dependence in the number of compounds studied showed that the introduction of a hydroxymethyl substituent to the base compound enhances the antiamnestic activity; the combination in the structure of both benzyl and methyl substituents provides a high anti-amnestic effect. The data obtained in this study indicate the prospects for the use of the leader compound as a new nootropic drug. The work expands and deepens the knowledge about the pharmacological properties of derivatives of 4-aminobutanoic acid and the leader compound of 4-(benzyl(methyl)amino) butanoic acid in terms of antiamnestic activity.