Two of the five new nicotinic acid derivatives proved to have the antihypoxic properties in tests with mice exposed to acute normobaric hypoxic hypoxia with hypercapnia. Specifically, LKhT 4–19 (100 mg/kg) extended lifetime of the animals by 11 %; LKhT 6-19 doses of 50 and 100 mg/kg extended lifetime by 23 and 34 %, respectively. The antihypoxic effect of LKhT 6–19 (50 mg/kg) outperformed in 1.2 times mexidol (substance of comparison) at the similar dose and was highly competitive at the dose of 100 mg/kg. For reference, mexidol is a 3-hydroxypyridine derivative (ethylmethylhydroxypyridine succinate incorporating, similar to the substances in question, the pyrydine heterocycle). Besides, LKhT 6–19 (100 mg/kg) outperformed mexidol at the similar dose in 1.1 times.

Introduction: The search for new drugs for the prevention and treatment of vascular cognitive disorders continues to be a relevant task of pharmacology. In this regard, the aim of this work is to study the antiamnestic effect of five new nicotinic acid derivatives in comparison with the well-known drug mexidol (ethylmethylhydroxypyridine succinate) in animals. Materials and methods: The experiments were carried out on white male mice using conditioned passive avoidance reflex (CPAR). Electroconvulsive shock (ECS), scopolamine administration, and acute hypoxia in a hermetic chamber were used as amnesic effects. Testing for the safety of CPAR was performed 24 h after amnesic exposure. The new substances, reference drug mexidol, and a 0.9% sodium chloride solution (control group) were administered once intraperitoneally 60 min before mice training. Results and discussion: Three of the five new nicotinic acid derivatives, LKhT 4-19 (100 mg/kg), LKhT 6-19 (25, 50, and 100 mg/kg), and LKhT 7-19 (100 mg/kg), have antiamnestic properties on models of amnesia in mice induced by ESC, scopolamine, and acute hypoxia in a hermetic chamber. At the same time, the most efficient substance – LKhT 6-19 – exceeds the reference drug mexidol on all three models used. In addition, this compound is also more efficient than two other new compounds, LKhT 4-19 and LKhT 7-19, on the model of ESC-induced amnesia and LKhT 7-19 on the scopolamine-induced amnesia model. Conclusion: Compound LKhT 6-19 is promising for further advanced preclinical studies as a potential drug with antiamnestic activity. Graphical abstract: