The Anxiolytic Potential of a New Series of Diazepinobenzimidazole Derivatives

Abstract

ФГАОУ ВО «Южный федеральный университет», научно-исследовательский институт физической и органической химииПроведено изучение анксиолитической активности нового ряда производных диазепинобензимидазола, имеющих в своей структуре две привилегированные подструктуры -диазепина и бензимидазола. По результатам проведенного исследования показано, что новый ряд соединений обладает анксиолитической активностью различной степени выраженности, что может свидетельствовать о высокой перспективности дальнейшего углубленного изучения нейропсихотропного потенциала новых соединений. Доказана анксиолитическая активность соединения под шифром ДАБ-19, превышающая показатели препарата сравнения диазепама.

Influence of Diazepino[1,2-a]benzimidazole derivative (DAB-19) on behavioral aspects of animals

“…The number of acts of compulsive burying was significantly reduced relative to the reference groups. The obtained data of DAB-19 and diazepam do not result from the development of a muscle relaxant effect, which is evident from the data of the previously conducted tests: Elevated Plus Maze (parameter of the total number of moves between the arms), Actometer and Open Field (Spasov et al 2018). According to the previously obtained data, tofisopam (2 mg/kg) was shown to have an anti-neurotic effect at the level of DAB-19 (2.34 mg/kg) -1.2 ± 0.49 marbles on average (Skripka et al 2018).…”

“…High spontaneous activity is probably associated with an increased search activity of mice. It can indicate either pronounced emotionality in the animals, which is not confirmed by the number of boluses as one of the observed parameters, or a positive effect on the cognitive aspect of the experimental rodents` behavior, which is supported by a distinct anxiolytic effect of DAB-19 in previous study (Spasov et al 2018).The suppression of natural fear of open spaces allows animals to show interest in exploring new territories. The anxiolytic effect of DAB-19 is also confirmed by a high number of entries to the central lit area, rarely recorded short-term self-groomings (which is known to indicate the nervous state of the animal) and a large number of acts of prolonged groomings (which is consistent with the results of screening and in-depth studies of the anti-anxiety activity of the compound) (Spasov et al 2018;Spasov et al 2020).…”

“…Perhaps, a combination of chemical compounds with a proven tranquilizing effect 6.0 ± 2.67 17.6 ± 3.68 11.4 ± 1.12* 5.6 ± 1.17* Diazepam (2 mg/kg) 5.1 ± 1.03* 9.5 ± 2.18* 10.5 ± 2.17* 2.4 ± 1.42 DAB-19 (2.34 mg/kg) 7.8 ± 1.18 1.5 ± 0.67* 12.8 ± 2.14 0.0 ± 0.01* Note: * -differences are significant compared to control (р ≤ 0.05, Kruskal-Wallis test, Dunn`s post hoc test). (Spasov et al 2018), carried out through various mechanisms, is manifested in DAB-19 in the multi-targeting of its action, which results in the reduction or leveling of a number of undesirable behavioral components.…”

“…The dose of (DAB-19) was equimolar to diazepam (2 mg/ kg), in which it demonstrates a pronounced anti-anxiety effect without muscle relaxation and sedation (Spasov et al 2018). Forty-eight outbred mice (n = 8/group) were randomly divided into six experimental groups.…”

“…In a previous study, we found a compound (DAB-19) -diazepino[1,2-a]benzimidazole, a derivative having in the core structure 2 privileged subclasses -diazepine and benzimidazole, showing a high tranquilizing action. It was shown that the compound demonstrated a pronounced anxiolytic effect not only comparable with a classic tranquilizer -diazepam, but exceeding it in a number of tests (Spasov et al 2018).…”