Comparative Effects of Liraglutide-R-Alpha Lipoic Acid Combination and Donepezil on Diazepam-Induced Amnesia in Rats.

INTRODUCTION: Cognitive impairment, including drug-induced amnesia, poses significant challenges in neurological research and therapy. Current treatments like donepezil provide limited benefits by targeting only cholinergic dysfunction. This study aimed to compare the cognitive-enhancing effects of the combination of liraglutide and R-alpha lipoic acid (R-ALA) with donepezil in a rat model of diazepam-induced amnesia. METHODS: Twenty adult Albino rats were randomized into four groups (n = 5 each): negative control, positive control (diazepam + saline), test (diazepam + liraglutide + R-ALA), and standard comparator (diazepam + donepezil). Diazepam (0.1 mg/kg, i.p.) induced amnesia, followed by treatments administered one hour before Morris Water Maze (MWM) trials. Escape latency times were recorded weekly at zero, one, two, three, and four hours post-treatment over five weeks. Data were analyzed by one-way ANOVA with Tukey's HSD post hoc test (p < 0.05). RESULTS: The liraglutide-R-ALA group showed a significant and progressive reduction in escape latency compared to the positive control across all weeks and time points, with mean differences at the four-hour mark, ranging from 39.3 to 48.5 seconds (p < 0.001). Compared to donepezil, this combination showed statistically significant superiority at the third and fourth hours in weeks 1-5 (p-values ranging from 0.001 to 0.0001), with mean latency reductions of up to 20.65 seconds at four hours in week 5. Donepezil produced moderate improvements with higher variability and less consistent significance. CONCLUSION: The liraglutide-R-ALA combination provides superior cognitive enhancement over donepezil in diazepam-induced amnesia by targeting multiple pathogenic mechanisms, highlighting the potential of multimodal therapies for cognitive impairment.