The effect of leukotriene-B4 receptor antagonist, SC-41930, on acetic acid-induced colonic inflammation.
SC-41930, 7-[3-(4-acetyl-3-methoxy-2-propylphenoxy)-propoxy]-3,4-dihydro-8-p ropyl- 2H-1-benzopyran-2-carboxylic acid, is a potent in vitro leukotriene-B4 (LTB4) receptor antagonist. LTB4 levels are elevated in colonic tissue of inflammatory bowel disease (IBD) patients which may account for the high degree of neutrophil (PMN) infiltration. The guinea pig acetic acid-induced colonic inflammation model has characteristics of IBD including PMN infiltration, edema, ulceration and necrosis. The model was used to evaluate the effect of SC-41930. SC-41930 was given orally, 30 min before and after intrarectal administration of 3% acetic acid. The PMN marker enzyme, myeloperoxidase, was measured along with histological evaluation to assess inflammation. Both parameters showed significantly less inflammation in SC-41930 treated animals with an oral ED50 of 20 mg/kg. These study results with an LTB4 receptor antagonist indicate a role for LTB4 in colonic inflammation and that an LTB4 receptor antagonist may be beneficial for treatment of IBD.
Fretland
D J
DJ
Department of Gastrointestinal Diseases Research, G. D. Searle and Co., Skokie, IL 60077.
Levin
S
S
Tsai
B S
BS
Djurić
S W
SW
Widomski
D L
DL
Zemaitis
J M
JM
Shone
R L
RL
Bauer
R F
RF
D000085:Acetates; D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology*; D003092:Colitis / Q000139:chemically induced* / Q000201:enzymology / Q000503:physiopathology; D006168:Guinea Pigs; D008297:Male; D009504:Neutrophils / Q000187:drug effects; D009195:Peroxidase / Q000378:metabolism; D011971:Receptors, Immunologic; D018102:Receptors, Leukotriene B4
D000085:Acetates; D001578:Benzopyrans; D011971:Receptors, Immunologic; D018102:Receptors, Leukotriene B4; C059950:SC 41930; D009195:Peroxidase