The role of glutamate in dementia.
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.
Department of Psychiatry, University of Göttingen, Federal Republic of Germany.
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Kornhuber
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Wiltfang
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J
Kornbuber
D000818:Animals; D003704:Dementia / Q000188:drug therapy / Q000378:metabolism*; D018691:Excitatory Amino Acid Antagonists / Q000627:therapeutic use; D018698:Glutamic Acid / Q000502:physiology*; D006801:Humans; D018696:Neuroprotective Agents / Q000627:therapeutic use; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors
D018691:Excitatory Amino Acid Antagonists; D018696:Neuroprotective Agents; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid