Abstract
We report the design and synthesis of a new diazepine derivative, 4-(4-methoxyphenyl)-2,3,4,5-tetrahydro-2,3-benzodiazepin-1-one (VBZ102), and the evaluation of its anxiolytic-like profile, memory impairment effect, and toxicity in Swiss mice. VBZ102 was evaluated for central nervous system effects in an open field, light–dark box, and novel object recognition tests under oral administration for acute and sub-acute treatment. We tested the VBZ102 toxicity in mice through a determination of LD50 values and examination of the biochemical and histopathological parameters. The VBZ102 induced an anxiolytic effect at different doses both in the light–dark box and open field tests. Unlike other benzodiazepines (e.g., bromazepam), a sedative effect was noted only after administration of the VBZ102 at 10.0 mg/kg.
Highlights
Anxiety is a normal physiological state that is beneficial in certain dangerous life situations and triggers the fight or flight stress response and physical symptoms resulting from the autonomic nervous system response
A majority of drugs used in anxiety treatment represent positive modulators of the gamma-aminobutyric acid (GABA) transmission, including benzodiazepine derivatives, and selective serotonin reuptake inhibitors (SSRIs) of different chemical natures [2,3]
Pharmacological activity in mouse behavmodels, and toxicity evaluation of the new compound 4-(4-methoxyphenyl)-2,3,4,5-tetraioral models, and toxicity evaluation of the new compound 4-(4-methoxyphenyl)-2,3,4,5hydro-2,3-benzodiazepin-1-one (VBZ102)
Summary
Anxiety is a normal physiological state that is beneficial in certain dangerous life situations and triggers the fight or flight stress response and physical symptoms resulting from the autonomic nervous system response. A majority of drugs used in anxiety treatment represent positive modulators of the gamma-aminobutyric acid (GABA) transmission, including benzodiazepine derivatives, and selective serotonin reuptake inhibitors (SSRIs) of different chemical natures [2,3]. A number of active molecules of this type have been synthesized over the past 40 years. Some of those compounds, e.g., tofisopam (Grandaxin® ), girisopam, nerisopam, possess significant anxiolytic and antipsychotic activities (Figure 1) [4]. There is a pressing need for the development of new active compounds with favorable side-effect profiles, credible benefits, and moderate costs. In the search for alternative and more specific molecules, current investigations are focused on the anxiolytic, sedative, and locomotor activities of various benzodiazepine derivatives. New potent anxiolytic dibenz-(1,4)-diazepin-1-one derivatives were recently synthesized [7]
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