Anand H, Roberts P J, Badman G, Dixon A J, Collins J F
Biochem Pharmacol. 1986 Feb 1;35(3):409-15. doi: 10.1016/0006-2952(86)90213-3.
On the basis of previous electrophysiological studies, it has been proposed that there are three main classes of excitatory amino acid receptor in the mammalian central nervous system, which are activated preferentially by kainic acid, quisqualic acid and N-methyl-D-aspartate respectively. Although the pharmacology of the N-methyl-D-aspartate receptor has been investigated extensively, potent and selective ligands which act at the kainate or quisqualate sites are lacking. In this study, we report that a number of novel kainate analogues possess either agonist or antagonist activity in a system which permits investigation of receptor-mediated coupled responses, viz. the ability of excitatory amino acids to elevate cyclic GMP concentrations in incubated cerebellar slices prepared from the adult rat. The data reported here provide some clues as to the likely structural requirements for developing effective kainate antagonists.
根据以往的电生理研究，有人提出在哺乳动物中枢神经系统中存在三类主要的兴奋性氨基酸受体，它们分别优先被海人酸、喹啉酸和N-甲基-D-天冬氨酸激活。尽管对N-甲基-D-天冬氨酸受体的药理学进行了广泛研究，但缺乏作用于海人酸或喹啉酸位点的强效和选择性配体。在本研究中，我们报告了一些新型海人酸类似物在一个允许研究受体介导的偶联反应的系统中具有激动剂或拮抗剂活性，即兴奋性氨基酸提高成年大鼠制备的离体小脑切片中环状鸟苷酸浓度的能力。此处报告的数据为开发有效的海人酸拮抗剂的可能结构要求提供了一些线索。
