The Novel Neuroprotective Action of Sulfasalazine through Blockade of NMDA Receptors

• Published in: The Journal of pharmacology and experimental therapeutics Vol. 305; no. 1; pp. 48 - 56
• Main Authors: Ryu, Bo Rum, Lee, Young Ae, Won, Seok Joon, Noh, Ji-Hyun, Chang, Su-Youne, Chung, Jun-Mo, Choi, Jun Sub, Joo, Choun Ki, Yoon, Sung Hwa, Gwag, Byoung Joo
• Format: Journal Article
• Language: English
• Published: United States American Society for Pharmacology and Experimental Therapeutics 01.04.2003
• Subjects: Animals; Antioxidants - pharmacology; Calcium - metabolism; Cells, Cultured; Cerebral Cortex - cytology; Cyclooxygenase 2; Disease Models, Animal; Ischemia - prevention & control; Isoenzymes - metabolism; Male; Mice; Mice, Inbred ICR; N-Methylaspartate - pharmacology; Neuroprotective Agents - pharmacology; Neuroprotective Agents - therapeutic use; NF-kappa B - metabolism; Prostaglandin-Endoperoxide Synthases - metabolism; Rats; Rats, Sprague-Dawley; Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors; Retinal Diseases - prevention & control; Sulfasalazine - pharmacology; Sulfasalazine - therapeutic use
• ISSN: 0022-3565; 1521-0103
• DOI: 10.1124/jpet.102.042606

Sulfasalazine is widely used to treat inflammatory diseases. Besides anti-inflammatory actions such as blockade of nuclear factor-κB and cyclooxygenases, we found that 30 to 1000 μM sulfasalazine dose dependently blocked N -methyl- d -aspartate receptor-mediated excitotoxicity without intervening kainate or α-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.