Development of memantine as a drug for Alzheimer’s disease: A review of preclinical and clinical studies

Abstract

Excitotoxicity contributes to neuronal cell death due to overstimulation of N-methyl-D-aspartate (NMDA) receptors by glutamate, which plays a significant role in the development and progression of Alzheimer’s disease (AD) and other neurodegenerative disorders. Studies have been conducted to identify a well-tolerated and selective NMDA receptor blocker in an effort to alleviate neurodegeneration. Memantine has been found to induce a distinct low-affinity NMDA receptor blockade in both preclinical and clinical studies Therefore, FDA approved this drug as a well-tolerated noncompetitive NMDA receptor blocker for treating moderate to severe cases of AD. Further, memantine showed neuroprotective effects in preclinical studies by selectively blocking excessive NMDA receptor activation. Altogether, this novel drug is well-tolerated and effective for treating moderate to severe AD in various clinical studies. This paper is a review of preclinical and clinical studies on the drug development process of memantine. Keywords: Memantine, Excitotoxicity, N-methyl-D-aspartate, Glutamate, Alzheimer’s disease, neurodegeneration