Watkins J C
Department of Pharmacology, School of Medical Sciences, Bristol, U.K.
Can J Physiol Pharmacol. 1991 Jul;69(7):1064-75. doi: 10.1139/y91-158.
Important findings in the excitatory amino acid (EAA) field that have stemmed directly from work initiated in chemical laboratories are discussed from a historical point of view, showing how each has contributed to our present knowledge of EAA receptors. The groups of compounds discussed include simple analogues and derivatives of short-chain excitatory amino acids, longer-chain analogues, analogues containing ring structures essential to the acidic nature of the omega-terminal, and conformationally restricted agonists and antagonists. Recent interest has centered on antagonists for the N-methyl-D-aspartate (NMDA) and alpha-methyl-3-hydroxy-5-methyl-isoxazole-4-propionic acid (AMPA) receptors typified by the long-chain omega-phosphono amino acids and the quinoxalinediones, respectively. Consideration of conformational aspects of both agonists and antagonists is currently providing considerable insight into the disposition of charged sites and general topological features in the various receptors, as well as the likely conformation adopted by L-glutamate in its physiological interaction with these receptors.
从历史角度讨论了在兴奋性氨基酸（EAA）领域中直接源于化学实验室所开展工作的重要发现，展示了每一项发现是如何为我们目前对EAA受体的认识做出贡献的。所讨论的化合物类别包括短链兴奋性氨基酸的简单类似物和衍生物、长链类似物、含有对ω-末端酸性性质至关重要的环状结构的类似物，以及构象受限的激动剂和拮抗剂。近期的研究兴趣集中在分别以长链ω-膦酰基氨基酸和喹喔啉二酮为代表的N-甲基-D-天冬氨酸（NMDA）和α-甲基-3-羟基-5-甲基异恶唑-4-丙酸（AMPA）受体的拮抗剂上。目前对激动剂和拮抗剂构象方面的研究正在为深入了解各种受体中带电位点的分布和一般拓扑特征，以及L-谷氨酸在与这些受体发生生理相互作用时可能采取的构象提供相当多的见解。
