Evaluation of psychotropic effects of a novel chromone-containing allylmorpholine derivative in BALB/c mice

Introduction. The search for effective approaches to the treatment of anxiety disorders, in particular, the development and study of drugs with anxiolytic action, is currently one of the most urgent tasks of neurobiological research. The study of behavioral changes in Danio rerio after exposure to a new group of substances – chromone-containing allylmorpholines – revealed their ability to exert dose-dependent sedation, and one of the compounds of the series – (E)-4-[3-(6-chloro-4-oxo-4H-chromene-3-yl)-4-cyclohexylallyl]morpholin-4-ium chloride (33a), in addition to sedative, also exerted anxiolytic action at low concentrations. Danio rerio is an evolutionary species much older than humans, and therefore the structural and functional differences between the receptors may be quite significant, making it necessary to evaluate the pharmacological profile of the new compounds in a translational model with more genetic similarities to humans, for example, in rodents.

Aim. The present study investigated the effects of 33a on anxiety behavior, cognitive functions, and grip strength of BALB/c mice after acute and chronic administration.

Materials and methods. Pharmacological activity was assessed using Open Field, Elevated Plus Maze, Light/Dark Box, T-maze, Marble burying, Tail suspension and Grip strength tests in BALB/c mice after acute administration of 33a at doses 1, 10 and 50 mg/kg, and two-week administration at doses 1 and 10 mg/kg.

Results and discussion. With acute administration, 33a at a dose of 50 mg/kg reduced the number of buried marbles, and at a dose of 10 mg/kg with chronic administration, it reduced the latency time of the first transition from a dark chamber to a white one in the Light/Dark Box test, which can be considered as manifestations of anxiolytic action. However, in the classical Elevated Plus Maze test, there were no statistically significant effects indicating the anxiolytic effect of 33a. The study did not reveal any negative effect of the studied substance on spatial memory and grip strength of mice, which may indicate the absence of its neurotoxic effect.

Conclusion. The results obtained confirmed the ability of compound 33a to exert dose-dependent inhibition of locomotor activity, however, this effect was not demonstrated in all tests. Further expansion of the range of used behavioral tests, as well as the use of experimental models may allow to reveal the specific activity of compound 33a, as well as other chromone-containing derivatives of allylmorpholine.

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