Excitotoxicity and N‐methyl‐D‐Aspartate receptors

Abstract

AbstractA great deal of new information has been generated over the past decade in the excitatory amino acid (EAA) field. Not only have endogenous EAA such as glutamate and aspartate become recognized as the leading neurotransmitter candidates at the majority of excitatory synapses in the mammalian central nervous system, but it is becoming increasingly evident that the well‐established neurotoxic (excitotoxic) properties of these agents may play an important role in the pathophysiology of neurodegenerative diseases. Several EAA receptor subtypes have been identified through which the excitotoxicity of EAA might be expressed. One of these—the N‐methyl‐D‐aspartate (NMDA) receptor—has become a primary focus of attention because of evidence suggesting it may be involved in a wide range of both neurophysiological and pathological processes. Antagonists that powerfully block both the excitatory and neurotoxic actions of EAA agonists at the NMDA receptor or associated ion channel have been identified and are being developed as potential neuroprotective agents for use in the management of neurological disorders. In this article, the potential role of excitotoxic mechanisms in neurodegenerative diseases and the prospects for controlling such disease processes by the application of antiexcitotoxin drugs will be examined.