Sulfasalazine and 5-Aminosalicylic Acid Inhibit Contractile Leukotriene Formation

Abstract

Sulfasalazine, used therapeutically in the treatment of ulcerative colitis, is cleaved in vivo to form 5-aminosalicylic acid (5-ASA) and sulfapyridine. In an isolated preparation of rat peritoneal cells both sulfasalazine (IC₅₀ = 0.15 mM) and 5-ASA (IC₅₀ = 2.3 mM), but not sulfapyridine, inhibited calcium ionophore-stimulated formation of contractile leukotriene activity. This activity, although not identified directly, is attributable to a mixture of leukotriene C₄ and leukotriene D₄ (commonly referred to as SRS-A, or slow-reacting substance of anaphylaxis). Reference compounds evinced expected activities (IC₅₀ = 0.024 mM for phenidone, IC₅₀ = 0.3 μM for nor-dihydroguaiaretic acid, IC₅₀ = 0.033 mM for BW 755C), whereas para-aminosalicylic acid and thiosalicylic acid were inactive. These properties of sulfasalazine may contribute to its therapeutic efficacy in vivo.

Key Words:

• 5-Aminosalicylic acid
• calcium ionophore
• LTC₄
• LTD₄
• SRS-A
• sulfasalazine