Effect of derivatives of (3-R-2-oxo-2H-[1,2,4]-triazino-[2,3-c]- quinazolin-6-il) carboxylic acids on the physical endurance under the conditions of hypoxia

Abstract

Background: The limited arsenal of actoprotectors by almost one bemethyl has caused the necessity to search the substances with the above action, suitable for the creation of a new drug on their basis. Material and methods: For the investigation the substances of 4 derivatives (3-R-2-oxo-2H-[1,2,4]- triazino -[2,3-C]-quinazolin-6-il) of carboxylic acids with the laboratory ciphers DSK-38, DSK-39, AV-224 and AV-227 have been taken. The studies have been performed on 84 nonlinear male rats weighing 165-220 g using two models of hypoxic states – circulatory hypoxia and acute hemic hypoxia, which differ by their starting formation mechanisms. Circulatory hypoxia has been modeled by unilateral occlusion of the right common carotid artery. The animals have been divided into 7 groups, 6 animals in each group. Results: It has been established that the course (15 days) intraperitoneal injections in rats with cerebral circulatory hypoxia model derivatives (3-R-2- oxo-2H-[1,2,4]-triazino-[2,3-c]-quinazolin-6-il) of carboxylic acid DSK-38 (4.8 mg/kg), DSK-39 (5.5 mg/kg), AV-224 (5.6 mg/kg) and AV-227 (6.9 mg/ kg) as well as bemethyl (34 mg/kg) cause an increase in dynamic (swimming test) and static (rotating rod) endurance of the animals. Similar changes in the physical endurance of rats have occurred in the prophylactic administration of the test substances in hemic hypoxia animals. According to the literature the compound DSK-38 also has cerebroprotective and analgesic activities. Conclusions: The compound DSK-38 is the leader as it has the largest actoprotective effect virtually mapped to bemethyl. A complex of effects inherent of DSK-38 compound indicates the advisability of the in-depth study of its pharmacological properties to find out its safety and suitability for creating a new drug on its basis.