Preclinical Data
Glutamate is the principal neurotransmitter in the brain. Glutamatergic overstimulation results in neuronal damage, a phenomenon that has been termed excitotoxicity. Such excitotoxicity ultimately leads to neuronal calcium overload and has been implicated in neurodegenerative disorders. Glutamate stimulates a number of postsynaptic receptors, including the N-methyl-D-aspartate (NMDA) receptor, which has been particularly implicated in memory processes, dementia, and the pathogenesis of Alzheimer’s disease.
Memantine is a NMDA receptor antagonist and protects the glutamatergic system from pathological activation. Clinically-relevant doses of memantine produce improvements in learning under conditions of tonic NMDA receptor activation in Alzheimer’s disease. In contrast to first generation therapies, memantine is likely to show neuroprotective effects at concentrations used in the treatment of Alzheimer’s disease and to slow down disease progression.
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