ANTIHYPOXIC ACTIVITY OF VARIOUS ETHYLMETHYLHYDROXYPYRIDINE SALTS

DOI: https://doi.org/10.29296/24999490-2020-04-05

D.Yu. Ivkin(1), D.S. Sukhanov(1), G.A. Plisko(1), A. S. Ivkina(1), M.V. Krasnova1, I.A. Titovich(1), E.D. Semivelichenko(1), I.L. Stepanova(1), V.P. Il’nickij(1), A.A. Karpov(2), S.V. Okovityi(1), A.V. Karshin(3) 1-St. Petersburg State Chemical Pharmaceutical University, Professor Popov str., b.14, lit. A, St. Petersburg, 197022, Russian Federation; 2-Almazov National Medical Research Centre, Akkuratova str., b.2, St. Petersburg, 197341, Russian Federation; 3-Farmamed LLC, Domostroitel’naya str., b. 16, lit. Е, St. Petersburg, 194292, Russian Federation E-mail: [email protected]

Introduction. The pathological state of hypoxia of the body occurs with an inadequate supply of tissues and organs with oxygen or with a violation of its utilization in the process of biological oxidation. Ethylmethylhydroxypyridine has a multi-component mechanism of action, which mediates its organ protective, antihypoxic, antioxidant, and anti-stress effects, allowing us to consider the drug as an auxiliary therapy for various pathological conditions. The aim of the study. Comparative assessment of the antihypoxic and antioxidant effects of various salts of ethylmethylhydroxypyridine (EMHP): acetylsalicylate, acetyl glutamate, orotate, succinate (Armadine, reproduced Mexidol preparation), salicylate, hydrochloride (methylethylpiridinol chloride) and metabolite of EMHP – Ethylmethylsulfopyridine (EMSP). Methods. Antihypoxic activity of substances in equimolar doses was studied in 320 outbred male mice weighing of 18–20 g, using 4 models of acute hypoxia: normobaric, histotoxic, hemic, hypercapnic. Results. There were confirmed the expressed anti-hypoxic activities of EMHP succinate. The EMHP salicylate was revealed to possess the most pronounced antihypoxic activity. EMSP, which is an active metabolite of EMHP succinate, showed pronounced activity in a model of acute histotoxic hypoxia (protection index = 69), as well as a weakly expressed antihypoxic effect in a model of hemic hypoxia. Conclusion. It is advisable to study the effectiveness of active substances in models of pathologies, based on the typical pathological process of hypoxia (diseases of the cardiovascular and nervous systems, liver), as well as assessing the effect on physical performance.
Keywords: 
ethylmethylhydroxypyridine succinate (Armadine), hypoxia, protection index, ethylmethylhydroxypyridine units
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