Vanillin Modulates the Sedative Effect of Diazepam, Possibly Through GABAergic Interaction Pathways in Thiopental Sodium‐Induced Sleeping Mice

ABSTRACT Insomnia is a common sleep disorder affecting approximately 10% of adults. This study aimed to evaluate the sedative effects of vanillin (VAN) and its combination with diazepam (DZP) in thiopental sodium (TS)‐induced sleeping mice. Mice received VAN (25 and 50 mg/kg, i.p.) or DZP (2 mg/kg, i.p.), followed by TS (20 mg/kg, i.p.) after 30 min to assess sleep latency and duration over 3 h. Additionally, we also used molecular docking and visualization to assess the VAN and DZP's GABA A receptor binding affinities and interactions. VAN significantly reduced sleep latency and prolonged sleep duration in a dose‐dependent manner. At 50 mg/kg, VAN decreased latency to 7.40 ± 1.44 min and increased sleep duration to 134.80 ± 6.82 min. When combined with DZP, VAN further enhanced sedative effects, reducing latency to 3.00 ± 0.83 min and extending sleep to 154.40 ± 7.4 min. Molecular docking showed that VAN binds to α 1 and β 2 subunits of the GABA A receptor with a −5.5 kcal/mol affinity and can cross the blood–brain barrier. These findings suggest that VAN has mild sedative effects and enhances the activity of DZP via GABAergic pathways, highlighting its potential as a complementary agent in sleep disorder management.