New 2,3-Benzodiazepine Derivative: Synthesis, Activity on Central Nervous System, and Toxicity Study in Mice

• Main Authors: Amal Amaghnouje, Serhii Bohza, Nathalie Bohdan, Imane Es-Safi, Andrii Kyrylchuk, Sanae Achour, Hinde El Fatemi, Dalila Bousta, Andriy Grafov
• Format: Article
• Language: English
• Published: MDPI AG 2021-08-01
• Series: Pharmaceuticals
• Subjects: benzodiazepines; central nervous system; mouse behavioral model; toxicity
• Online Access: https://www.mdpi.com/1424-8247/14/8/814

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.