What is the role of glutamate blockers in the treatment of epilepsy?

Updated: Jan 28, 2020
  • Author: Juan G Ochoa, MD; Chief Editor: Selim R Benbadis, MD  more...
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Glutamate and aspartate are the most two important excitatory neurotransmitters in the brain. The glutamate system is a complex system that contains macromolecular receptors with different binding sites (ie, alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid [AMPA], kainate, N -methyl-D-aspartate [NMDA], glycine, and metabotropic sites).

The AMPA and the kainate sites open a channel through the receptor, allowing sodium and small amounts of calcium to enter. The NMDA site opens a channel that allows large amounts of calcium to enter along with the sodium ions. This channel is blocked by magnesium in the resting state. The glycine site facilitates the opening of the NMDA receptor channel. The metabotropic site is regulated by complex reactions and its response is mediated by second messengers.

NMDA antagonists have a limited use because they produce psychosis and hallucinations. In addition to these adverse effects, learning and memory may be impaired by blocking these receptors, because NMDA receptors are associated with learning processes and long-term potentiation.

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