Department of Pharmacology of the Military Medical Academy in the 21st century: New achievements based on historical traditions (2000–2023)

Abstract

In the early 2000s at the Department of Pharmacology, active research was launched into the mechanisms of hypoxia, creation of antihypoxic drugs, study of means and technologies for increasing performance, and drugs with immunomodulatory and reparative effects. The mechanisms of hypoxia and life support in extreme conditions have been a traditional area of scientific research of the department. Starting back in the 1960s under the leadership of V. M. Vinogradov, this direction gained development and scientific recognition by the end of the 1990s. During this period, new antihypoxants of direct and indirect actions were created and thoroughly studied, namely, gutimin, bemithyl, amtizol, trimetazidine, and others. Nearly all employees of the department and numerous applicants for academic degrees from among both academic and nonacademic employees participated in the research. The use of approaches and concepts of molecular physiology and pharmacology achieved very interesting and promising results for implementation. An unconditional success in scientific research in this area has been the elucidation of the molecular mechanisms of action of aminothiol-type antihypoxants, which consist in optimizing energy production and energy consumption in cells and the ability of compounds to reduce membrane damage caused by lipid peroxidation and clearly activate antioxidant systems. The second direction was the study of the molecular mechanisms of sustainable adaptation to various factors, which was started by Prof. A. V. Smirnov. Thus, long-term adaptation patterns were established in the body’s adaptation to high-altitude hypoxia, overheating, and heavy repeated loads. The contribution of individual organs to the development of these adaptive phenomena was quantitatively determined. In the experiment, effective schemes for emergency adaptation were developed using “pulse modes” of training influences against the use of pharmacological adaptogens. A significantly more pronounced adaptogenic activity has been established for drugs such as thiobenzimidazole (bemythyl) and trecrezan in comparison with known adaptogens, such as dibazole and eleutherococcus. Based on experimental data, similar schemes for pharmacologically enhanced and accelerated emergency adaptation have been developed and tested on healthy volunteers, particularly to sharp changes in climatic conditions (overheating, hypothermia, and hypoxia) and metabolic cocktails based on the antihypoxant bemityl (B-100, B-200, and B-300). These schemes and pharmacological interventions make it possible, in just a few days, to make the body noticeably adapt to the action of certain climatic factors. The third direction was the creation and study of new pharmacological agents for the correction of the effects of hypoxia, toxic pulmonary edema, and liver and immune system damage based on condensed indole systems and their product transformations. Consequently, indole derivatives (approximately 60 compounds have been synthesized and studied) are low toxic and have antihypoxic, antiedema, hepatoprotective, actoprotective and antiviral activities.