Alzheimer’s disease is one of the most serious neurodegenerative disorders occurring mainly in the old age. It results into memory and cognitive impairment leading to inability to perform routine tasks in day to day life and worsening of quality of life. Excitotoxic-neurodegeneration caused by over functioning of glutamatergic transmission is of the main pathophysiological aspects. Glutamate release is mainly mediated by sodium channels and blockade of these channels decreases the excessive release of this excitatory neurotransmitter. The previous study has already revealed Mexiletine, a sodium channel blocker established as an anti-arrhythmic agent, as a remedy in progressive Alzheimer’s disease caused by excitotoxicity. It was found out that Mexiletine averted memory impairment in mice which were administered aluminum chloride to produce Excitotoxic-neurodegeneration. The protective effect was evident in animal models of passive avoidance and elevated plus maze and was comparable with standard drug Memantine. Fluorometric estimation was undertaken to measure amount of glutamate present in homogenates of animal brains of each group animals. Brain homogenates of animals treated with Mexiletine exhibited low fluorescence indicating low amount of glutamate, while that of positive control group animals showed significantly higher fluorescence and presence of higher amount of glutamate. Brain homogenates with Memantine also showed less amount of glutamate released probably because of its capacity to block calcium channels and not sodium channels. It is well stipulated that beneficiary effect of Mexiletine in the treatment of Alzheimer’s disease is attributed to its capacity to block sodium channels, control release of glutamate and ultimately averting Excitotoxic-neurodegeneration.
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