Memantine is an uncompetitive antagonist with moderate affinity for NMDA receptors, and it demonstrates voltage-dependency and relatively fast on/off receptor kinetics. Agents such as memantine which mimic some of the features of the endogenous antagonist magnesium may be an optimal treatment combining both neuroprotective activity with symptomatological improvement. The latter can be explained on the basis of a decrease in the noise level and restoration of a sufficient "signal to noise" ratio. Memantine protects cultured neurons from excitotoxin-induced cell-death. The drug dose-dependently prevented glutamate-induced cell death in rat cerebellar, cortical, mesencephalic and hippocampal neurons and calcium ion-induced death in retinal ganglions obtained from rats. Memantine exerts neuroprotective effects in several models of brain injury. The drug attenuated loss of cholinergic neurons in the CNS induced by injection of NMDA into the basal forebrain of rats. At a dosage of 5-10 mg/kg in rats, memantine induced production of brain-derived neurotrophic factor (BDNF), a substance shown to promote survival and differentiation of CNS neurons. Due to the preclinical effects of memantine brought about by its anti-ischemic and anti-excitotoxic properties, recent clinical efficacy has been demonstrated in patients with advanced dementia of vascular origins. We will discuss the role, the potential benefits and the results obtained in the field.