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The novel neuroprotective action of sulfasalazine through blockade of NMDA receptors.

Authors
Ryu, BR; Lee, YA; Won, SJ; Noh, JH; Chang, SY; Chung, JM; Choi, JS; Joo, CK; Yoon, SH; Gwag, BJ
Citation
The Journal of pharmacology and experimental therapeutics, 305(1):48-56, 2003
Journal Title
The Journal of pharmacology and experimental therapeutics
ISSN
0022-35651521-0103
Abstract
Sulfasalazine is widely used to treat inflammatory diseases. Besides anti-inflammatory actions such as blockade of nuclear factor-kappaB and cyclooxygenases, we found that 30 to 1000 micro M sulfasalazine dose dependently blocked N-methyl-D-aspartate receptor-mediated excitotoxicity without intervening kainate or alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid neurotoxicity. The neuroprotective effects of sulfasalazine were attributable to prevention of Ca(2+) influx and accumulation through N-methyl-D-aspartate receptors as a low-affinity antagonist. The systemic administration of sulfasalazine reduced neuronal death following transient cerebral and retinal ischemia in adult rat. The present findings suggest that the neuroprotective action of sulfasalazine can be therapeutically applied to halt devastating neuronal death following hypoxic ischemia, trauma, and neurodegenerative diseases.
MeSH terms
AnimalsAntioxidants/pharmacologyCalcium/metabolismCells, CulturedCerebral Cortex/cytologyCyclooxygenase 2Disease Models, AnimalIschemia/prevention & controlIsoenzymes/metabolismMaleMiceMice, Inbred ICRN-Methylaspartate/pharmacologyNF-kappa B/metabolismNeuroprotective Agents/pharmacology*Neuroprotective Agents/therapeutic useProstaglandin-Endoperoxide Synthases/metabolismRatsRats, Sprague-DawleyReceptors, N-Methyl-D-Aspartate/antagonists & inhibitors*Retinal Diseases/prevention & controlSulfasalazine/pharmacology*Sulfasalazine/therapeutic use
DOI
10.1124/jpet.102.042606
PMID
12649352
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Pharmacology
AJOU Authors
곽, 병주
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