Neuroprotection by a novel NMDAR functional glycine site partial agonist, GLYX-13

Patric K. Stanton, Pamela E. Potter, Jennifer Aguilar, Maria Decandia, Joseph R. Moskal

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

GLYX-13 (threonine-proline-proline-threonine-amide) is an amidated di-pyrrolidine that acts as a functional partial agonist at the glycine site on N-methyl-D-aspartate glutamate receptors (NMDARs). GLYX-13 can both increase NMDAR conductance at NR2B-containing receptors, and reduce conductance of non-NR2B-containing receptors. Here, we report that GLYX-13 potently reduces delayed (24 h) death of CA1 pyramidal neurons produced by bilateral carotid occlusion in Mongolian gerbils, when administered up to 5 h post-ischemia. GLYX-13 also reduced delayed (24 h) neuronal death of CA1, CA3, and dentate gyrus principal neurons elicited by oxygen/glucose deprivation in in-vitro hippocampal organotypic slice cultures, when applied up to 2 h post-oxygen/glucose deprivation. The glycine site full agonist D-serine completely occluded neuroprotection, indicating that GLYX-13 acts by modulating activation of this site.

Original languageEnglish (US)
Pages (from-to)1193-1197
Number of pages5
JournalNeuroreport
Volume20
Issue number13
DOIs
StatePublished - Aug 2009

Keywords

  • Coagonist
  • Glycine site
  • Ischemia
  • NMDA receptor
  • Partial agonist
  • Stroke

ASJC Scopus subject areas

  • Neuroscience(all)

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