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5,7-Dichlorokynurenic acid, a potent and selective competitive antagonist of the glycine site on NMDA receptors

Authors
Journal
Neuroscience Letters
0304-3940
Publisher
Elsevier
Publication Date
Volume
120
Issue
1
Identifiers
DOI: 10.1016/0304-3940(90)90157-5
Keywords
  • Nmda
  • Glycine
  • Xenopusoocyte
  • Kynurenic Acid
  • Kainate

Abstract

Abstract Fourteen substituted derivatives of kynurenic acid were compared for their ability to block ionic currents evoked by N- methyl- d-aspartate (NMDA) plus glycine, or kainate, in voltage-clamped Xenopus oocytes injected with rat brain messenger RNA. Among these analogues there was an excellent correlation between the K i for displacing [ 3H]glycine binding to rat brain membranes, and the ability to inhibit ionic currents evoked by glycine/NMDA in Xenopus oocytes. In the oocyte 5,7-dichlorokynurenic acid (5,7-DCK) was a competitive blocker of the glycine recognition site on NMDA receptors, and was more potent ( K B 65 nM in Schild analysis) and selective (509-fold more potent vs glycine than kainate) than the prototype glycine antagonist, 7-chlorokynurenic acid. 5,7-DCK also reduced NMDA-induced neuron injury in rat cortical cell cultures.

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