[Glutamate-related excitotoxicity neuroprotection with memantine, an uncompetitive antagonist of NMDA-glutamate receptor, in Alzheimer's disease and vascular dementia].
OBJECTIVE
To review the therapeutic efficacy of memantine, an uncompetitive antagonist of N-methyl-D-aspartate (NMDA)-glutamate receptor.


METHODS
Alzheimer's disease (AD) is the most common neurodegenerative disorder and cause of dementia with ageing worldwide. The main AD symptoms are a gradual loss of cognitive function and a functional impairment. Glutamatergic excitatory neurotransmission, an important process in learning and memory, is severely disrupted in AD, probably due to the oxidative stress associated with the beta-amyloid peptide (1-42) increase. The glutamate-related excitotoxicity, mainly mediated by NMDA subtype of the glutamate receptors, is a common clue of pathogenesis for neurodegenerative disorders.


CONCLUSIONS
Memantine, a moderate-affinity, voltage-dependent, uncompetitive antagonist of NMDA receptor, shows neuroprotective effects in patients with moderate-to-severe AD. Memantine is a drug with neuroprotective and cognition-enhanced properties, which can be combined with other treatments for AD. Thus, memantine does not stop or reverse AD, but its moderating effect in protecting the brain from the toxic levels of calcium, allows normal signaling among brain neurons. The efficacy and safety profile of memantine have been reported in several clinical trials for treatment of AD and vascular dementia.
Tanović
A
A
Facultat de Biologia, Universitat de Barcelona, Avda. Diagonal 645, E-08028 Barcelona, Spain.
Alfaro
V
V
D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D002986:Clinical Trials as Topic; D018691:Excitatory Amino Acid Antagonists / Q000627:therapeutic use*; D018698:Glutamic Acid / Q000378:metabolism*; D006801:Humans; D008559:Memantine / Q000627:therapeutic use*; D015394:Molecular Structure; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism
D018691:Excitatory Amino Acid Antagonists; D018696:Neuroprotective Agents; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D008559:Memantine