NEUROTOXICOLOGICAL PROFILE OF 5-НТ2А-ANTAGONIST OF IMIDAZOBENZIMIDAZOLE DERIVATIVE

Thearticlepresentstheresultsofastudyoftheneurotoxicologicalprofileofanew5-HT2A-antagonist(compoundI) using the method of multi-test observation by «S. Irwin». The test parameters were evaluated in parallel groups, receiving the compound in doses beginning with the average effective dose (ED50) and with a multiple increase of 2, 5, 7.5 and 10 times.

The study revealed that the neurotoxicological properties of compound I are characterized by dose-dependent activity. It has been shown that neurotoxicological changes in the behavior of the animals did not occur with the administration of compound I at average effective dose of 10 mg / kg and doses, exceeding the effective by 2 and 5 times; the animals welfare corresponds to that of the control group. The most significant effects by the administration of the studied compound developed in high doses, exceeding the effective by 7.5 and 10 times. The limits of the minimum toxic dose (TDmin) for compound I by oral administration has been found to be 50 mg / kg <TDmin≤75 mg / kg.

1. Spasov A.A. etc. Derivatives, imidazo [1, 2a]benzimidazole as antagonists of 5-HT2Areceptors. Bioorganic chemistry, 2016, 42, 4, p, 440-447.

2. Spasov A.A., Anisimova V.A., Yakovlev D.S., Petrov V.I., Minkin, V.I. Agents exhibiting properties of antagonist of serotonin 5-НТ2А-receptors. Patent of Russia №2465901, 2012 (in Russian).

3. Maltsev D.V. et al. Structural and functional dependence of the derivatives of benzimidazole and indole in the development of 5-НТ2А-ergic activity. Vestnik of Volgograd State Medical University, 2014, p. 78-79 (in Russian).

4. Morkovin JV. et al. Adrenergic and serotonergic activity of new compounds with antimigraine properties. Volgograd scientific medical journal, 2017, 1 (in Russian).

5. Yakovlev D.S. et al. The effect of 5-HT2A antagonists on blood flow inthe vessels of the carotid system in the conditions of increased level of serotonin. Bulletin of experimental biology and medicine, 2014, 157, p. 328-330 (in Russian).

6. Maltsev D.V. et al. Study of analgesic activity of a compound with 5-HT2Aantagonistic activity of RU-4Modern high technologies, 2013, 9, p. 56-57 (in Russian).

7. Morkovina Ya.V., Maltsev D.V., Yakovlev D.S. The study of toxicity and antiserotonin properties of compounds RU-31 and RU-4Actual problems of experimental and clinical medicine, 2015, p. 328-329 (in Russian).

8. Irwin S. Determinetion of varIbility in drug response. Psychosometics, 1964, 5, p. 174-179.

9. Yakovlev D.S. et al. Target-oriented approach to the development of medicines for the treatment of migraine. Experimental and clinical pharmacology, 2018, 81, p. 278-278.

10. Kovalev D.G., Bugaeva L.I., Ozerov A.A. The neurotoxicological profile of new derivatives of adenine possessing antiviral activity. Saratov journal of medical scientific research, 2010, 6 (in Russian).