Anti-inflammatory effects of BX661A, a novel therapeutic drug for ulcerative colitis.

To clarify the mechanism of action of 5- [4- (2-carboxyethylcarbamoyl) -phenylazo] -salicylic acid disodium salt dehydrate (BX661A) as a therapeutic drug for ulcerative colitis, we investigated the effects on carrageenin edema, adjuvant arthritis, polymorphonuclear leukocyte (PMN) chemotaxis and degranulation of mesenteric mast cell, and following results were obtained.1. Although BX661A, salazosulfapyridine (SASP), 4-aminobenzoyl-β-alanine (4-ABA) and sulfapyridine (SP) did not inhibit the carrageenin edema at pretreatment for 30 min, BX661A and SASP showed the inhibitory effect on carrageenin edema at pretreatment for 8 hrs.2. SASP showed the slight therapeutic effect on adjuvant arthritis, but BX661A and 5-aminosalicylic acid (5-ASA) had no effect.3. BX661A, SASP and SP dose-dependently inhibited the PMN chemotaxis induced by zymosan-treated serum, N-formyl-methionyl-leucyl-phenylalanine (FMLP) and leukotriene B4 (LTB4) . 4-ABA only inhibited the FMLP-induced chemotaxis. On the other hand, 5-ASA at concentration up to 10 mM exhibited almost no effects on all PMN chemotaxis.4. BX661A, SASP and SP dose-dependently inhibited the mast cell degranulation induced by compound 48/80, substance P and IgE. 5-ASA showed the inhibitory effects on compound 48/80 and IgE-induced mast cell degranulation, but 4-ABA only inhibited the IgE-induced degranulation.From these results, it was suggested that inhibitory effect of BX661A on carrageenin-induced edema may be due to 5-ASA, further that inhibitory effects on PMN chemotaxis activity and degranulation of mesenteric mast cell partially may be concerned in therapeutic effects of BX661A on ulcerative colitis.