Influence of new dimethylaminoethanol derivatives, butanoic and trans-butenedioic acids, on the tolerability of hypoxia, hyperthermia, and hypothermia

BACKGROUND: The need to increase the tolerance of various extreme effects is associated not only with the expansion of human professional activity regions but also with the need to assist victims of natural and man-made disasters. The use of pharmacological agents for individual adverse effects is a well-known method; however, considering the combined effects of several physical or chemical factors, only a few references are found in the literature.

AIM: This preclinical study aimed to examine 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 temperature (hyperthermia and hypothermia).

MATERIALS AND METHODS: The fumaric salt of the amber ether of diethylaminoethanol was synthesized at St. Petersburg State University of Chemistry and Pharmacy, Department of Organic Chemistry (Head Professor I.P. Yakovlev). The study was conducted 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 40°C, and tolerance to hypothermia by the time of maximum swimming in water at 10–12°C. Under combined exposure, the condition of the animals was assessed by the dynamics of physical performance, hypoxia was induced by preliminary administration of the methemoglobin former sodium nitrite at a dose of 50 mg/kg, and thermal exposure was induced by placing the animal in water at 40°C (hyperthermia) or 9–11°C (hypothermia).

RESULTS: After a single intragastric administration in a wide range of doses, the test compound stimulated the physical performance of animals and exhibited 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 and 50 mg/kg).

CONCLUSION: Fumaric salt of dimethylaminoethanol amber ether, a new derivative of dimethylaminoethanol, butenedioic, and trans-butenedioic acids, is promising for further study as a means of increasing the body’s resistance to extreme influences.