title: A novel non-NMDA receptor antagonist shows selective displacement of low-affinity [3H]kainate binding.
abstract: 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.
authors.affiliation: NeuroSearch A/S, Glostrup, Denmark.
authors.forename: T H
authors.initials: TH
authors.lastname: Johansen
authors.forename: J
authors.initials: J
authors.lastname: Drejer
authors.forename: F
authors.initials: F
authors.lastname: Wätjen
authors.forename: E O
authors.initials: EO
authors.lastname: Nielsen
mesh_terms: D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002122:Calcium Chloride / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D018691:Excitatory Amino Acid Antagonists; D007211:Indoles / Q000378:metabolism*; D007608:Kainic Acid / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D015394:Molecular Structure; D009467:Neuromuscular Depolarizing Agents / Q000494:pharmacology; D010091:Oximes / Q000378:metabolism*; D011810:Quinoxalines / Q000494:pharmacology; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D014316:Tritium
chemical_list: D018691:Excitatory Amino Acid Antagonists; D007211:Indoles; D009467:Neuromuscular Depolarizing Agents; D010091:Oximes; D011810:Quinoxalines; D014316:Tritium; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; C084273:5-nitro-6,7,8,9-tetrahydrobenzo(G)indole-2,3-dione-3-oxime; C012301:domoic acid; D002122:Calcium Chloride; D007608:Kainic Acid; D002118:Calcium