The study of antidepressant properties of new 1,2,3-triazolo-1,4-benzodiazepine derivatives

Abstract

Anxiety-depressive disorders are among the most common mental health conditions and often cause significant functional impairment, affecting a person’s quality of life. Research conducted in recent years indicate the importance of studying and searching for new substances based on benzodiazepines, in particular triazolobenzodiazepines, for the treatment of anxiety states and disorders, as well as determining the presence of other biological activities of these compounds. Aim. To study the antidepressant activity of new derivatives of 1,2,3-triazolo-1,4-benzodiazepines in the Porsolt forced swim and tail suspension tests. Materials and methods. The antidepressant activity of new 1,2,3-triazolo-1,4-benzodiazepine derivatives under the code MA-252, MA-253, MA-254, MA-255 and MA-261 was studied in the Porsolt forced swim and tail suspension tests. The following behavioral reactions, such as the latent period of the first immobility (more than 5 seconds), the total duration of immobility (staying in a stationary state), the number of immobile episodes, were recorded. Results and discussion. During the study, a decrease in the total duration of immobility, the main indicator of “despair” of animals, and an increase in the latent period of the first immobility were monitored. It may indicate the manifestation of antidepressant properties of new 1,2,3-triazolo-1,4-benzodiazepine derivatives. The indicator of the antidepressant activity in groups of animals administered MA-253, MA-254 and MA-255 derivatives in all doses was higher among the groups studied. The depression index was the lowest when MA-253 and MA-254 derivatives were used in the dose of 1 mg/kg, and was not statistically significantly different from that in the group receiving imipramine in the dose of 25 mg/kg. According to the results of the tail suspension test, 1,2,3-triazolo-1,4-benzodiazepine derivatives MA-253, MA-254 and MA-255 showed a significant decrease in the total duration of immobilization by 69.4 %, 47.1 % and 33.1 %, respectively, in relation to the control group (p<0.05), as well as an increase in the latent period of the onset of the first immobility episode by several times. Conclusions. A decrease in the duration of immobility in mice injected with 1,2,3-triazolo-1,4-benzodiazepine derivatives gives grounds to draw a conclusion that animals develop a state of “behavioral despair” and exhibit antidepressant properties.