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

Abstract

Introduction: Diazepino[1,2-a]benzimidazole derivatives showed anxiolytic (EPM, L/D box, Vogel test), antidepressant (Tail Suspension test, Porsolt test), anticonvulsant (Pentylenetetrazole-Induced seizures) and analgesic (Tail-Flick, Hot Plate) actions, which were described earlier (Spasov et al. 2020). 11-(4-tert-butylbenzyl)-2,3,4,5-tetrahydro[1,3]diazepino[1,2-a]benzimidazole hydrobromide (compound DAB-19) has evident anxiolytic, antidepressant and anticonvulsant effects. In the present study, compound DAB-19 was screened for its influence on animals` behavior patterns, such as aggression, obsessive-compulsive behavior, emotional lability, and unsociability. Materials and methods: 112 outbred white animals (rats and mice) were used. Compound DAB-19 (2.34 mg/kg, p.o.) and diazepam (2 mg/kg, p.o.) were injected to the treatment groups. Using an Open Field (OF) test, we evaluated a spontaneous motor activity, a search activity of mice and a degree of their emotionality. During a Marble Burying (MB) test, we monitored anxiolytic and anticompulsive effects of DAB-19. Using a Resident-intruder (RI) test, we evaluated a degree of aggression in the experimental animals, properties of their social interaction, as well as defensive and individual behavior. Results and discussion: Compound DAB-19 has positive influence on the search activity, mood stabilizing activity and antiaggressive actions. Administration of both DAB-19 (2.34 mg/kg, p.o.) and diazepam (2 mg/kg, p.o.) reduced anxiety-like behavior in OP, RI and MB tests, as indicated by a significantly increased number of entries to the center of OP; a decreased number of marbles buried in MB and reduced aggressive behavior in RI. It was stated that using DAB-19 leads to a decrease in affective reactions of the animals – aggression, obsessive-compulsive behavior, neurotic condition and emotional instability. Conclusions: The compound (DAB-19) produces anxiolytic-like effects, compared with those of diazepam, in various anxiety paradigms.

Consensus Ensemble Multitarget Neural Network Model of Anxiolytic Activity of Chemical Compounds and Its Use for Multitarget Pharmacophore Design

“…For two groups of synthesized andexperimentally studied novel highly active substances with laboratory codes, DAB 11-substituted 2,3,4,5-tetrahydro-11H-[1,3]diazepino[1,2-a]benzimidazoles [ 34 , 35 ] and RD3,6-disubstituted [1,2,4]triazolo[3,4-a][2,3]benzodiazepines [ 36 ] (4 compounds in each group) using the methods described above in this article, optimized 3D models were built and ensemble docking was performed. Using the LigPlot+ v2.2 program [ 22 ], for the most energetically favorable conformation at the site of a specific target, the key points of interaction between the structure of the analyzed molecule and the amino acids of this protein were determined.…”

A Comprehensive Account on Recent Progress in Pharmacological Activities of Benzimidazole Derivatives

“…Maltsev et al ( Maltsev et al, 2020 ) evaluated a series of Diazepino[1,2-a]benzimidazole derivatives for their possible psychotropic properties. Compound 522 at a dose of 2.34 mg/kg showed prominent anxiolytic, antidepressant and anticonvulsant activities in both rat and mice models.…”

Screening of anxiolytic properties and analysis of structure-activity relationship of new derivatives of 6-(4-methoxy)-7H-[1,2,4]triazolo[3,4-a][2,3]benzodiazepine under the code RD

“…Within 5 minutes of the test, the number of transitions between the quadrants (horizontal locomotor activity), the number of rearings (vertical locomotor activity), the number of holes examined (exploratory activity), and the number of entries to the center of the unit were recorded. In addition to the behavioral activity of the animals, the OF technique also made it possible to assess the nonspecific muscle relaxant capacity of new compounds (Maltsev et al 2020). A battery of muscle relaxation tests -Rotarod, Grid, and Wire -were described previously (Spasov et al 2020b).…”