The N-methyl-D-aspartate (NMDA) receptor complex is a subtype of glutamate receptor and its dysfunction is involved in many neurological disorders associated with aging, including chronic pain, depression, stroke and Parkinson's disease. Multiple clinical trials using NMDA receptor antagonists have been aborted mainly due to the severe psychomimetic adverse effects of these drugs that occur before concentrations can reach an adequate level in the brain. In this review, we present the evidence that clinically safer NMDA antagonists such as memantine and nitroglycerin, and the combination drug nitro-memantine, are promising as drugs in treating neurodegenerative diseases.