STUDY OF NOOTROPIC AND ANTI-HYPOXIC ACTIVITY OF 5-AMINO-3-EXO-AZATRICYCLO[5.2.1.0^2,6]DECAN-4-ON

Introduction. Nootropic drugs are components of complex therapy for various neurological dysfunctions. One of the classes of ND are pyrrolidone derivatives, which, in addition to a direct effect on cognitive functions, increase the brain's resistance to hypoxia.

Aim. The work was to study the effect of the 3-aminopyrrolidin-2-one derivative containing the norbornane fragment (P-11) on different memory phases in rats and to evaluate its antihypoxic properties.

Materials and methods. The effect of P-11 on memory was assessed on passive avoidance test (PAT) in rats. The antihypoxic properties of P-11 were studied on a model of acute normobaric hypoxia with hypercapnia, assessing the life span of laboratory animals and the level of lipid peroxidation processes in the brain.

Results and discussion. It was shown that the introduction of P-11 at different stages of the development of passive avoidance reaction improves the ability of animals to learn and extract a memorable trace of pain stimulation 24 hours after the development of a reflex. On a model of normobaric hypoxia with a single injection, P-11 showed a tendency to increase the life span of rats relative to the control, and with a 14-day treatment, pronounced antihypoxic properties were observed compared with other pyrrolidone derivatives, pyracetam and phenotropil, which manifested in an increase in life span of mice, as well as in lowering lipid peroxidation processes in brain tissue.

Conclusion. Thus, it was shown that a new derivative 3-aminopyrrolidin-2-it exhibits nootropic and antihypoxic properties.

1. Vakhitova Yu. V., Antipina E. I., Yamidanov R. S., Khisamutdinova R. Yu. Identification of target genes 5-amino-exo-3-azatricyclo [5.2.1.02,6] decan-4-one in vivo model of arrhythmia. Bioorganic chemistry. 2011; 6 (37): 9–11. Doi.org/10.1134/S1068162011060148 (In Russ.).

2. Mironov A. N. Bunatjan N. D. Guidelines for conducting preclinical studies of drugs. – M.: Grief and K, 2012; 944 р. (In Russ.).

3. Modern methods in biochemistry / Under. ed. Acad. V. N. Orekhovich. – M.: Medicine. 1977; Pp. 66–68 (In Russ.).

4. Khisamutdinova R. Yu., Sapozhnikova T. A., Makara N. S., Gabdrakhmanova S. F., Zarudii F. C. Experimental study of the antiarrhythmic activity and chronic toxicity of 5-amino-exo-3- azatricyclo [5.2.1.02,6] decan-4-one. Drugs development & registration. 2015; 2 (11): 90–93 (In Russ.).

5. Tsypysheva I. P., Koval’skaya A. V., Makara N. S., Lobov A. N., Petrenko I. A., Galkin E. G., Sapozhnikova T. A., Zarudii F. C., Yunusov M. S. Synthesis and specific nootropic activity of derivatives (-)-cytisine, having in its structure fragments of carbamides and thiocarbamides. Chemistry of natural compounds. 2012; 4: 565. Doi.org/10.1007/s10600-012-0329-7. (In Russ.).

6. Martino M. V., Guandalini L., Mannelli L. C. Di, Menicatti M., Bartolucci G., Dei S., Manetti D., Teodori E., Ghelardini C., Romanelli M. Piperazines as nootropic agents: New derivatives of the potent cognition-enhancer DM235 carrying hydrophilic substituents. Bioorganic and Medicinal Chemistry. 2017; 25: 1795–1803. DOI: 10.1016/j.bmc.2017.02.019.

7. Tsypysheva I. P., Koval’skaya A. V., Lobov A. N., Makara N. S., Petrova P. R., Farafontova E. I., Zainullina L. F., Vakhitova Yu. V., Zarudii F. S. Synthesis and nootropic activity of new 3-amino-12-nmethylcytisine derivatives. Chemistry of Natural Compounds. 2015; 5(51): 910–915. Doi.org/10.1007/s10600-015-1446-x.

8. Zveiniece L., Svalbe B., Veinberg G., Grinberga S., Vorona M., Kalvinsh I., Dambrova M. Investigation into stereoselective pharmacological activity of phenotropil. Basic and Clinical Pharmacology and Toxicology. 2011; 109: 407–412. Doi.org/10.1111/j.1742-7843.2011.00742.x.