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

  • Neurosci Lett. 1990 Nov 27;120(1):17-20. doi: 10.1016/0304-3940(90)90157-5.
D McNamara  1 ,  E C Smith ,  D O Calligaro ,  P J O'Malley ,  L A McQuaid ,  R Dingledine
Affiliations
  • 1. Department of Pharmacology, University of North Carolina, Chapel Hill 27599.
PMID: 2149877 DOI: 10.1016/0304-3940(90)90157-5
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 Ki 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 (KB 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.

Products