The majority of rapid excitatory transmission in the nervous system is mediated by glutamate-activated ion channels. Ionotropic glutamate receptors have been subdivided pharmacologically into AMPA (cx-amino-3-hydroxy-5methyl-Cisoxazole propionic acid), KA (kainate), and NMDA subtypes (Monaghan et al., 1989). These receptors have been implicated in a number of physiological and pathological processes. During development glutamate receptors are involved in neuronal differentiation, migration, and activity-dependent synapse formation (Balazs et al., 1989; Brewer, 1989; Komoru and Rakic, 1993). In mature neurons, long-term potentiation and long-term depression require ionotropic glutamate receptors. Glutamate-gated ion channels also play a central role in mediating the excitotoxic effects of glutamate (Olney, 1990). Pathophysiological processes thought to involve glutamate excitotoxicity and neurodegeneration include epilepsy stroke, Parkinson’s disease, Alzheimer’s disease, Huntington’s disease, and amyotrophic lateral sclerosis.
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