Neuroprotective Effect of Famotidine in Mouse Models of Alzheimer's Disease

Background: Famotidine is a competitive histamine H-receptor antagonist that reduces the formation of stomach acid and is used to treat gastrointestinal disorders associated with acid reflux, gastroesophageal reflux disease, duodenal ulcer, gastric ulcer, and pathological hypersecretory disorders. This study is designed to investigate the possible neuroprotective effects of the ranolazine scopolamine-induced Alzheimer's disease-like feature in a mouse model. Methods: Mice were divided equally into five groups (ten mice per group), including control group and induction group. The mice in the induction group were administered scopolamine 1 mg/kg i.p., once daily for 7 days, to induce features similar to Alzheimer's disease. The mice in the remaining three treatment groups were given tested medications prophylactically for 14 days. After that the induction was carried out with scopolamine 1 mg/kg i.p., once daily, while the tested medication dosages were continued for an additional 7 days. These treatment groups included: the donepezil group (5 mg/kg/day), the famotidine group (40 mg/kg/day) and the combined group with donepezil (5 mg/kg/day) and famotidine (40 mg/kg/day); all were administrated i.p., once daily. Behavioral parameters were assessed, among others with the Y-maze test and novel object recognition test, and the inflammatory cytokines and oxidative stress parameters were assessed as well. Results: Famotidine exhibits significant improvements in behavior and memory, level of oxidative stress parameter, and inflammatory cytokines. Conclusions: Famotidine and its combination at prescribed doses in the current study improved learning and memory impairments in mice model of Alzheimer's disease probably via their antioxidant and anti-inflammatory properties confirmed by a significant increase in antioxidant mediator and a significant decrease in oxidative stress marker and inflammatory cytokines. (Clin. Lab. 2024;70:1483-1489. DOI: 10.7754/Clin.Lab.2024.240147