Excitotoxic Amino Acids and Neuropsychiatric Disorders

Abstract

A wealth of new information pertaining to excitatory amino acids (EAA) has been generated over the past two decades. The prototypic EAA, glutamate (Glu) and aspartate (Asp), which are abundantly present in the mammalian central nervous system, have become recognized as Jekyll and Hyde mole­ cules that serve vitally important metabolic and neurotransmitter functions while simultaneously harboring treacherous neurotoxic potential. The neurotoxicity of Glu and Asp, although first described 30 years ago, was relatively ignored until studies in the early 1970s linked the phenomenon to an excitatory mechanism. In subsequent years, mechanisms underlying ex­ citotoxic phenomena have been further elucidated, several EAA receptor subtypes have been delineated, drugs with anti-excitotoxic actions have been identified, and evidence for the potential complicity of excitotoxins in neurodegenerative disorders has begun to unfold. A specific subtype of EAA receptor, the N-methyl-D-aspartate (NMDA) receptor, has become a primary focus of attention because of evidence implicating it in a wide range of both neurophysiological and pathological processes. Evidence for the involvement of other EAA receptor subtypes in human neuropathological syndromes has also begun to appear and there is basis for believing that central neurons may be particularly vulnerable to excitotoxic degeneration during certain periods of development and in old age. Here I review highlights of research de-