RT Journal Article SR Electronic T1 Novel antagonists of the inhibitory glycine receptor derived from quinolinic acid compounds. JF Molecular Pharmacology JO Mol Pharmacol FD American Society for Pharmacology and Experimental Therapeutics SP 1200 OP 1206 VO 50 IS 5 A1 V Schmieden A1 S Jezequel A1 H Betz YR 1996 UL http://molpharm.aspetjournals.org/content/50/5/1200.abstract AB Binding of the coagonist glycine to the N-methyl-D-aspartate (NMDA) subtype of glutamate receptors is potently antagonized by 2-carboxy-4-hydroxyquinolines. We show that closely related derivatives, 4-hydroxy-quinolines and 4-hydroxquinoline-3-carboxylic acids, antagonize the agonist response of the recombinant inhibitory glycine receptor (GlyR). In Xenopus laevis oocytes expressing the GlyR alpha 1 subunit, the chloride-substituted derivatives 5,7-dichloro-4-hydroxyquinoline-3-carboxylic acid and 7-chloro-4-hydroxyquinoline inhibited glycine currents in a mixed high affinity competitive and low-affinity noncompetitive fashion, whereas the related compounds 7-trifluoromethyl-4-hydroxyquinoline-3-carboxylic acid and 7-trifluoromethyl-4-hydroxyquinoline showed purely competitive antagonism. Our data suggest a model of the pharmacophore of the GlyR that displays significant similarity to that proposed for the glycine binding site of the N-methyl-D-aspartate receptor.