The Glycine Site on the NMDA Receptor: Pharmacology and Involvement in NMDA Receptor-Mediated Neurodegeneration
It is now firmly established that the widespread actions of the excitatory amino acid neurotransmitters glutamate and aspartate in the mammalian central nervous system (CNS) are mediated by distinct receptor sub-types. Amongst these, the N-methyl-D-aspartate (NMDA) receptor has been characterized most fully in terms of its pharmacological and biophysical properties (Watkins and Evans, 1981; Mayer and Westbrook, 1987). The NMDA receptor can be divided into three functional domains (Foster and Fagg, 1987): a transmitter recognition site, an ion channel and an allosteric site activated by glycine. This chapter will review the glycine site on the NMDA receptor, describe its pharmacology, including the identification of selective antagonists, and discuss experiments with these compounds which have attempted to determine the relevance of activation of the glycine site in vivo for neurodegenerative phenomena mediated by NMDA receptor activation.
KeywordsNMDA Receptor Excitatory Amino Acid Quinolinic Acid Kynurenic Acid Excitatory Amino Acid Receptor
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