Modulatory Sedative Activity of Abrine on Diazepam in Thiopental Sodium Mediated Sleeping Mice: An In Vivo Approach with Receptor Binding Affinity of GABAergic Transmission

Abstract

The current study aims to assess the effects of abrine (ABR) in thiopental sodium (TS)‐induced sleeping mice and to explore the sedative impacts of the compound by using in vivo and in silico investigations. ABR (5 and 10 mg k−1g, i.p.) and diazepam (DZP) (2 mg k−1g, i.p.) were administered to the experimental animals either single or combined. TS (20 mg k−1g, i.p.) was administered to induce sleep, and latency with sleeping duration was observed for 3 h. The in silico investigation was conducted to predict the role of ABR in the gamma‐aminobutyric acid A (GABAA) receptor in the sleeping process and to evaluate pharmacokinetics and toxicity. Results showed that ABR (10 mg k−1g) significantly (p < 0.05) decreased the latency period (8.20 ± 1.85 min) and enhanced sleep duration (187.8 ± 8.87 min) in comparison with the control group. Additionally, the co‐treatments of ABR and DZP remarkably reduced the latency period (4.40 ± 0.24 min) and increased the sleeping duration (201.40 ± 5.89 min) compared to the single therapy. The molecular docking indicated that ABR has a binding affinity of −7.4 kcal/mol for the GABAA receptor. In conclusion, ABR provides strong sedative and synergistic efficacy on TS‐induced sleeping mice via the GABAergic system.