Antihypoxic properties of ethylthiobenzimidazole succinate

Background. 2-Ethylthiobenzimidazole succinate (I) is a new compound created by analogy with the domestically produced drug metaprot (bemitil), which is a hydrobromide salt of 2-ethylthiobenzimidazole (II). The aim of the study was to compare the antihypoxic effects of compounds I and II in two models of normobaric hypoxia in mice. Methods. Mice were randomized into 8 groups (n = 8-12 mice in each), which were subjected to normobaric hypoxia: 1) in a cupping test and 2) a hypoxic chamber with a variable gas composition, changing the oxygen concentration in the gas mixture from 21% to 2% by displacing it with nitrogen. Compounds I and II were administered intraperitoneally once 1 hour before hypoxia at doses of 50 and 100 mg/kg. Results. In the cupping test (hypoxia with hypercapnia), both compounds significantly increased the survival time of mice by 13-21%, with the dose of 50 mg/kg being more effective. Under normobaric hypoxia with variable gas composition, the survival time of mice at critical oxygen concentrations decreasing from 6 to 2 vol% oxygen increased by 108% (from с 8.2±1.1 min to 17.0±1.7 min, р0.05) after the administration of compound I and by 135% (to 19.3±2.2 min, р0.01) after the administration of compound II. The threshold oxygen concentration at which mice survived, on the contrary, decreased from 4.56±0.16% in the control to 3.23±0.26% after the introduction of compound I and to 2.97±0.30% – compound II, i.e., to 71±6% and 65±7% of the initial values, respectively. Finally, the assessment of hypoxia resistance in points changed from 4.0±0.5 in the control to 8.8±0.7, which amounted to 220±18% (p0.01), and 9.5±0.8 points, or 238±20% (p0.001), after the introduction of compound I and compound II, respectively. Conclusion. Compounds I and II at doses of 50 and 100 mg/kg exert a pronounced antihypoxic effect in two variants of normobaric hypoxia models in mice, and the antihypoxic effect is similar in magnitude for both compounds. The mechanism of the antihypoxic action of compounds I and II is apparently similar and is associated with the 2-ethylthiobenzimidazole molecule rather than with the anionic part of the molecule.