B. NMDA-receptor antagonist memantine

Antagonists of the NMDA-glutamate receptor are often neuroprotective, preventing the loss of neurons following ischemic and other injuries. Memantine is a dimethyl adamantane derivative. Memantine acts by physically blocking the NMDA receptor–associated ion channel, but, at therapeutic doses, only a fraction of these channels are actually blocked. This partial blockade may allow memantine to limit Ca2+ influx into the neuron, such that toxic intracellular levels are not achieved during NMDA-receptor overstimulation, while still permitting sufficient Ca2+ flow through unblocked channels to preserve other vital processes that depend on Ca2+ (or Na+) influx through these channels. This is in contrast to psychotoxic agents such as phencyclidine, which occupy and block nearly all of these channels. In short term studies, memantine has been shown to slow the rate of memory loss in both vascular-associated and Alzheimer dementia in patients with moderate to severe cognitive losses. However, there is no evidence that memantine prevents or slows the neurodegeneration in patients with Alzheimer disease or is more effective than the AChE inhibitors. Memantine is well tolerated, with few dose-dependent adverse events.