Glutamate is the principal neurotransmitter in the brain. 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: Glutamatergic overstimulation results in neuronal calcium overload and, ultimately, in neuronal damage, a phenomenon that has been termed excitotoxicity. Over time, excitotoxic effects lead to neuronal cell death, i.e. to neurodegeneration.
Memantine is an NMDA receptor antagonist and protects the glutamatergic system from pathological over-activation by excess glutamate levels. 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.