title: The novel neuroprotective action of sulfasalazine through blockade of NMDA receptors.
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.
authors.affiliation: Department of Neuroscience and Pharmacology, Center for the Interventional Therapy of Stroke and Alzheimer's Disease (CITSAD), Ajou University School of Medicine, Suwon, Kyunggi-do, Korea.
authors.forename: Bo Rum
authors.initials: BR
authors.lastname: Ryu
authors.forename: Young Ae
authors.initials: YA
authors.lastname: Lee
authors.forename: Seok Joon
authors.initials: SJ
authors.lastname: Won
authors.forename: Ji-Hyun
authors.initials: JH
authors.lastname: Noh
authors.forename: Su-Youne
authors.initials: SY
authors.lastname: Chang
authors.forename: Jun-Mo
authors.initials: JM
authors.lastname: Chung
authors.forename: Jun Sub
authors.initials: JS
authors.lastname: Choi
authors.forename: Choun Ki
authors.initials: CK
authors.lastname: Joo
authors.forename: Sung Hwa
authors.initials: SH
authors.lastname: Yoon
authors.forename: Byoung Joo
authors.initials: BJ
authors.lastname: Gwag
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D051546:Cyclooxygenase 2; D004195:Disease Models, Animal; D007511:Ischemia / Q000517:prevention & control; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D016202:N-Methylaspartate / Q000494:pharmacology; D016328:NF-kappa B / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D012164:Retinal Diseases / Q000517:prevention & control; D012460:Sulfasalazine / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000975:Antioxidants; D007527:Isoenzymes; D016328:NF-kappa B; D018696:Neuroprotective Agents; D016194:Receptors, N-Methyl-D-Aspartate; D012460:Sulfasalazine; D016202:N-Methylaspartate; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D002118:Calcium