Johansen T H, Drejer J, Wätjen F, Nielsen E O
NeuroSearch A/S, Glostrup, Denmark.
Eur J Pharmacol. 1993 Aug 15;246(3):195-204. doi: 10.1016/0922-4106(93)90031-4.
5-Nitro-6,7,8,9-tetrahydrobenzo[G]indole-2,3-dione-3-oxime (NS-102), a new competitive glutamate receptor antagonist displaced binding to non-N-methyl-D-aspartate (non-NMDA) binding sites with no activity at the NMDA and strychnine-insensitive glycine binding sites. Under experimental conditions in which both high- and low-affinity sites were labelled, NS-102 only partially inhibited the binding of [3H]kainate. Studies of NS-102 displacement of high-affinity versus low-affinity [3H]kainate binding showed a high selectivity of NS-102 for the low-affinity [3H]kainate binding site (Ki = 0.6 microM) compared to the high-affinity [3H]kainate binding site (Ki > 10 microM). NS-102 was a relatively weak inhibitor of 2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionic acid (AMPA) binding (IC50 = 7.2 microM). NS-102 and related compounds with similar pharmacological profiles may become valuable tools in the characterization of the functional importance of the low-affinity [3H]kainate binding site.
5-硝基-6,7,8,9-四氢苯并[G]吲哚-2,3-二酮-3-肟（NS-102）是一种新型竞争性谷氨酸受体拮抗剂，它能取代与非N-甲基-D-天冬氨酸（非NMDA）结合位点的结合，而对NMDA和士的宁不敏感的甘氨酸结合位点无活性。在高亲和力和低亲和力位点均被标记的实验条件下，NS-102仅部分抑制[3H]海人酸的结合。对NS-102取代高亲和力与低亲和力[3H]海人酸结合的研究表明，与高亲和力[3H]海人酸结合位点（Ki>10 microM）相比，NS-102对低亲和力[3H]海人酸结合位点具有高选择性（Ki = 0.6 microM）。NS-102是2-氨基-3-（3-羟基-5-甲基异恶唑-4-基）丙酸（AMPA）结合的相对较弱抑制剂（IC50 = 7.2 microM）。NS-102及具有相似药理特性的相关化合物可能成为表征低亲和力[3H]海人酸结合位点功能重要性的有价值工具。
