Preclinical study of the influence of a new dimethylaminoethanol derivative, butandioic and trans-butenedioic acids on the tolerability of hypoxia, hyperthermia and hypothermia

Abstract

Introduction. The need to increase the tolerance of various extreme impacts is associated not only with the expansion of the regions of human professional activity, but also with the need to provide assistance to victims in the centers of natural disasters and man-made disasters. The use of pharmacological agents for this purpose for individual adverse effects is a well-known method, however, with regard to the combined effect of several physical or chemical factors, only a few references are found in the literature. In this regard, the purpose of this work was a preclinical study of the effectiveness of a new derivative of aminoethanol and intermediates of the Krebs cycle in relation to the isolated and combined effects of hypoxia and the temperature factor (hyperthermia and hypothermia). Materials and methods. The compound under study was synthesized at the Department of Organic Chemistry at the Department of Organic Chemistry (Head Professor I.P. Yakovlev). The study was performed on small laboratory animals. Resistance to hypoxia was assessed by the dynamics of the altitude threshold of animals, tolerance to hyperthermia - by survival in a thermal chamber at a temperature of +40 C, tolerance to hypothermia - by the time of maximum swimming in water with a temperature of 10-12 C. Under combined exposure, the condition of the animals was assessed by the dynamics of physical performance, hypoxia was created by preliminary administration of the methemoglobin former sodium nitrite at a dose of 50 mg/kg, thermal exposure - by placing the animal in water with a temperature of 40 C (hyperthermia) or 9-11 C (hypothermia). Results. The test compound after a single intragastric administration in a wide range of doses stimulates the physical performance of animals and exhibits a protective effect under the isolated effects of hypobaric hypoxia, hyperthermia and hypothermia. With combined exposure to hemic hypoxia and hyperthermia, the compound was effective at a dose of 250 mg/kg, with combined exposure to hemic hypoxia and hypothermia, efficiency was also noted at lower doses (25, 50 mg/kg). Conclusion. A new derivative of dimethylaminoethanol, butanedioic and trans-butenedioic acids is promising for further study as a means of increasing the body's resistance to extreme effects.