Preliminary Evaluation of Anxiolytic-Like Activity of Selected Antihistaminic Drugs Using the Elevated Plus Maze Model in Wistar Albino Rats

Background: Anxiety disorders remain a significant neuropsychiatric burden, and limitations of existing anxiolytic drugs have encouraged interest in repurposing established medications. Antihistamines differ in central nervous system penetration, suggesting possible variation in anxiety-related behavioral effects. Objective: To evaluate and compare the anxiolytic-like activity of cetirizine and promethazine using the Elevated Plus Maze model in Wistar albino rats, with diazepam as the standard reference drug. Methods: Adult Wistar albino rats were divided into four groups with six animals in each group. The control group received normal saline; the standard group received diazepam 3 mg/kg; and the test groups received cetirizine 2 mg/kg and promethazine 2 mg/kg. Treatments were administered orally, and behavioral assessment was performed 60 minutes after administration. Time spent in open-arm entries, closed-arm entries, and total-arm entries was recorded. Data were expressed as mean ± SD and analyzed using one-way ANOVA followed by Tukey’s post hoc test. Results: Control animals showed the lowest open arm time and open arm entries. Diazepam showed the highest open-arm exploration and promethazine showed higher responses than cetirizine. Open arm time increased from 87.75 ± 5.57 sec in control animals to 149.25 ± 14.70 sec with diazepam, 139.62 ± 9.62 sec with promethazine, and 118.40 ± 2.98 sec with cetirizine. Total arm entries were comparable to or higher than control across treatment groups. Conclusion: Promethazine and cetirizine demonstrated anxiolytic-like effects, with promethazine showing stronger activity. These hypothesis-generating findings warrant further investigation of antihistamines in anxiety-related behavioral models.