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

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.

journal_name

Neuroreport

journal_title

Neuroreport

authors

Stanton PK,Potter PE,Aguilar J,Decandia M,Moskal JR

doi

10.1097/WNR.0b013e32832f5130

subject

Has Abstract

pub_date

2009-08-26 00:00:00

pages

1193-7

issue

13

eissn

0959-4965

issn

1473-558X

journal_volume

20

pub_type

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