Neuroprotective effect of ranolazine and famotidine in a mouse model of Alzheimer’s disease

Introduction. The neurodegenerative disorder known as Alzheimer’s disease progresses over time as it causes damage to different parts of the brain. Ranolazine, a piperazine derivative, is a treatment that is considered to be of secondary relevance for persistent aortic stenosis in individuals with stable angina who do not react to other drugs. Additionally, famotidine is a competitive H2-receptor antagonist that reduces stomach acid secretion and treats conditions such as acid reflux and ulcers. In mouse models, ranolazine may help protect the brain against Alzheimer’s disease-like characteristics induced by scopolamine.

Aim. To examine the potential neuroprotective properties of the combined administration of ranolazine and famotidine in mitigating symptoms of Alzheimer’s disease in a mouse model induced by scopolamine.

Materials and methods. The experiment included four groups of ten mice each: a control group, an induction group that received 1 mg/kg of scopolamine intraperitoneally once a day for seven days to mimic Alzheimer’s disease symptoms, and a memory loss group that received no such medication. For the remaining two groups of mice, the following medications were given orally once daily: donepezil (5 mg/kg/d) and a combination of ranolazine (40 mg/kg/d) and famotidine (40 mg/kg/d). After 14 days of prophylactic medication, the induction was performed with scopolamine (1 mg/kg i.p. once daily), and the medication was continued for an additional week. Research on the brain tissue sample included histopathological examinations, evaluation of inflammatory cytokines and oxidative stress parameters (such as acetylcholinesterase concentration), and assessment of behavioral parameters (such as novel object recognition and Y-maze tests).

Results and discussion. Scopolamine significantly impaired behavior (Y-maze 53.72, p ≤ 0.001), which was reversed by treatments (donepezil: 67.58, p ≤ 0.001). Treatments significantly reduced oxidative stress (MDA 1.65, p < 0.01) and inflammation (TNF-α 125.91, p ≤ 0.001) compared to the induction group. All treated groups showed no significant difference compared to controls (p > 0.05). In comparison to the scopolamine group, ranolazine and famotidine combination significantly improved behavioral and memory performance, oxidative stress parameters, and inflammatory cytokine levels. However, there was no significant reduction in the concentration of acetylcholinesterase in brain homogenate.

Conclusion. Ranolazine and famotidine protected mice from scopolamine-induced AD-like symptoms in this study. The recent investigation showed that ranolazine and famotidine's antioxidant and anti-inflammatory actions may explain this benefit.

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