Glutamatergic agents for AD

One of the pathological hypotheses suggested to cause AD is neurotoxic mechanisms resulting is excessive amounts of amino acids being released. AD patients have a loss of glutametergic pyramidal neurons, while the receptors NMDA (N-methyl-D-aspartate) are preserved. An over stimulation of these receptors could lead to neuronal loss. Memantine, an NMDA blocker, is effective in treating severe AD. The drug has been approved in Germany since 1970’s, but clinical trial data to support its use have been limited. Data from recent clinical trials investigating the safety and clinical efficacy of memantine show that it is effective for moderate to severe AD. The medication is still being studied and is approved in the US and several European countries. 17

Reviewer’s conclusions on Memantine: There is a short-term beneficial effect of memantine compared to placebo for patients with moderate to severe AD. The effect of memantine in patients with vascular dementia, Alzheimer disease and dementia of non-specified type at six weeks showed that there were beneficial effects on cognition, activities of daily living, and behaviour and in global impression of change. The drug is well tolerated and the incidence of adverse effects is low. However, most of the trials so far reported have been small and not long enough to detect clinically important benefits long term, therefore more studies that are extended in duration are needed to determine the efficacy of memantine