The role of glutamate in dementia

  • J. Kornbuber
  • J. Wiltfang
Part of the Journal of Neural Transmission. Supplementa book series (NEURAL SUPPL, volume 53)


Glutamate is an excitatory neurotransmitter, but may also act as an endogenous neurotoxin. There is good evidence for an involvement of the glutamatergic system in the pathophysiology of dementia. The glutamatergic transmission machinery is quite complex and provides a gallery of possible drug targets. There are good arguments both for an agonist and an antagonist strategy. When following the antagonist strategy, the goal is to provide neuroprotective effects via glutamate receptor antagonisms without inhibiting the physiological transmission that is required for learning and memory formation. When following the agonist strategy, the goal is to activate glutamatergic transmission without neurotoxic side effects. Several available antidementia drugs may modulate the glutamatergic transmission.

The pathogenesis of the most frequent type of dementia, i.e. Alzheimer’s disease, is poorly understood. Currently, there is an enormous need for an effective pharmacotherapy that either slows the rate of progression or produces clinically significant improvement in symptoms. This short overview describes the role of the excitatory neurotransmitter glutamate in Alzheimer’s disease. Glutamate is the transmitter used, e.g., in corticocortical association neurons and in intrahippocampal fibers. Glutamatergic mechanisms are involved in fast synaptic transmission as well as in learning and memory processes. But, under certain conditions, glutamate may become a neurotoxin leading to slowly progressive as well as acute neuronal cell loss. These properties of the glutamatergic system led to the hypothesis that there might be a glutamatergic strategy for the treatment of Alzheimer’s disease and also other dementia syndromes (Greenamyre et al., 1985; Greenamyre et al., 1988; Lawlor and Davis, 1992).


NMDA Receptor NMDA Receptor Antagonist Quinolinic Acid Domoic Acid Glutamatergic Transmission 


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Copyright information

© Springer-Verlag Wien 1998

Authors and Affiliations

  • J. Kornbuber
    • 1
  • J. Wiltfang
    • 1
  1. 1.Department of PsychiatryUniversity of GöttingenGöttingenFederal Republic of Germany

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