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

6,7,8,9-tetrahydrobenzo[G]indole-2,3-dione-3-oxime (NS-102), a new com petitive glutamate receptor antagonist displaced binding to non-N-meth yl-D-aspartate (non-NMDA) binding sites with no activity at the NMDA a nd strychnine-insensitive glycine binding sites. Under experimental co nditions in which both high- and low-affinity sites were labelled, NS- 102 only partially inhibited the binding of [H-3]kainate. Studies of N S-102 displacement of high-affinity versus low-affinity [H-3]kainate b inding showed a high selectivity of NS-102 for the low-affinity [H-3]k ainate 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 i nhibitor of amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionic acid (A MPA) binding (IC50 = 7.2 muM). NS-102 and related compounds with simil ar pharmacological profiles may become valuable tools in the character ization of the functional importance of the low-affinity [H-3]kainate binding site.