Vol. 305, Issue 1, 48-56, April 2003

The Novel Neuroprotective Action of Sulfasalazine through Blockade of NMDA Receptors

Bo Rum Ryu, Young Ae Lee, Seok Joon Won, Ji-Hyun Noh, Su-Youne Chang, Jun-Mo Chung, Jun Sub Choi, Choun Ki Joo, Sung Hwa Yoon and Byoung Joo Gwag

Departments 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 (B.R.R., Y.A.L., S.J.W., B.J.G.); Department of Life Sciences and Center for Cell Signaling Research (CCSR), Ewha Womans University, Daehyun-Dong, Seodaemun-Gu, Seoul, Korea (J.-H.N., S.-Y.C., J.-M.C.); Laboratory of Opthalomology and Visual Science, Catholic University, Research Institute of Medical Science, Banpo-dong, Seocho-gu, Seoul, Korea (J.S.C., C.K.J.); and Department of Molecular Science and Technology, Ajou University, Suwon, Kyunggi-do, Korea (S.H.Y.).

Sulfasalazine is widely used to treat inflammatory diseases. Besides anti-inflammatory actions such as blockade of nuclear factor-B and cyclooxygenases, we found that 30 to 1000 µM sulfasalazine dose dependently blocked N-methyl-D-aspartate receptor-mediated excitotoxicity without intervening kainate or -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid neurotoxicity. The neuroprotective effects of sulfasalazine were attributable to prevention of Ca²⁺ 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.