Sulfasalazine and 5-aminosalicylic acid inhibit contractile leukotriene formation.
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 microM for nordihydroguaiaretic 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.
D000636:Aminosalicylic Acids / Q000494:pharmacology*; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002469:Cell Separation; D019804:Mesalamine; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D010529:Peritoneal Cavity / Q000166:cytology; D051381:Rats; D011919:Rats, Inbred Strains; D013189:SRS-A / Q000096:biosynthesis*; D013427:Sulfapyridine / Q000494:pharmacology; D012460:Sulfasalazine / Q000494:pharmacology*
D000636:Aminosalicylic Acids; D013189:SRS-A; D000001:Calcimycin; D012460:Sulfasalazine; D019804:Mesalamine; D013427:Sulfapyridine