[Pharmacological studies of BX661A. 5-[4-(2-carboxyethylcarbamoyl)-phenylazo]-salicylic acid disodium salt dihydrate (1). Therapeutic effects on dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) model in rats].
In the present study, we investigated the therapeutic effects of 7- or 14-day treatment with BX661A or salazosulfapyridine (SASP) in the DSS-induced UC model in rats. BX661A (10-300 mg/kg, p.o.) dose-dependently decreased the erosion area and the shortening of the large intestine. On the other hand, SASP (30 and 100.mg/kg, p.o.) dose-dependently decreased the erosion area in the treatment for 14 days (on the contrary, % inhibition of erosion area was reduced by the dose of 300 mg/kg), but did not improve the shortening of the large intestine. Secondly, we investigated the therapeutic effects of 5-aminosalicylic acid (5-ASA), 4-aminobenzoyl- beta-alanine (4-ABA) and sulfapyridine (SP) by intrarectal administration on the DSS-induced UC model in rats. 5-ASA significantly decreased the erosion area in the large intestine and improved the length of the large intestine of rats that was shortened by ingesting DSS. On the other hand, 4-ABA and SP improved neither the shortening nor the erosion area of the large intestine. These results suggest that BX661A may be clinically effective and useful in the treatment of patients with ulcerative colitis. Furthermore, it was suggested that 5-ASA may be the active moiety for the therapeutic effects of BX661A and SASP.
Kimura
I
I
Preclinical Development Laboratories, Nippon Hoechst Marion Roussel Ltd., Shiga, Japan.
Nagahama
S
S
Kawasaki
M
M
Kataoka
M
M
Sato
M
M
D000284:Administration, Oral; D000636:Aminosalicylic Acids / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D000873:Anthracenes / Q000627:therapeutic use; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D000897:Anti-Ulcer Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D003093:Colitis, Ulcerative / Q000139:chemically induced / Q000188:drug therapy*; D016264:Dextran Sulfate; D008297:Male; D019804:Mesalamine; D010659:Phenylhydrazines; D051381:Rats; D017207:Rats, Sprague-Dawley; D013427:Sulfapyridine / Q000627:therapeutic use; D012460:Sulfasalazine / Q000627:therapeutic use
D000636:Aminosalicylic Acids; D000873:Anthracenes; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000897:Anti-Ulcer Agents; D010659:Phenylhydrazines; D012460:Sulfasalazine; D019804:Mesalamine; C048796:4-(2-anthryl)butanoic acid; D016264:Dextran Sulfate; C038637:balsalazide; D013427:Sulfapyridine