A NOVEL NON-NMDA RECEPTOR ANTAGONIST SHOWS SELECTIVE DISPLACEMENT OF LOW-AFFINITY [H-3] KAINATE BINDING

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 [H-3]kainate. Studies of NS-102 displacement of high-affinity versus low-affinity [H-3]kainate binding showed a high selectivity of NS-102 for the low-affinity [H-3]kainate binding site (K(i) = 0.6 muM) compared to the high-affinity [H-3]kainate binding site (K(i) > 10 muM). NS-102 was a relatively weak inhibitor of 2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionic acid (AMPA) binding (IC50 = 7.2 muM). NS-102 and related compounds with similar pharmacological profiles may become valuable tools in the characterization of the functional importance of the low-affinity [H-3]kainate binding site.