Gastric antisecretory and anti-ulcer effect of ME3407, a new benzimidazole derivative, in rats.
The effects of a new benzimidazole derivative, ME3407 (n-butyl-2-(thiazolo-[5,4-b]pyrid-2-yl) sulfinylacetate, CAS 133903-90-9), on gastric acid secretion and gastric and duodenal ulcers in rats were examined. ME3407, given orally, inhibited dose-dependently (0.3-30 mg/kg) the incidence of gastric lesions such as Shay ulcers, and water-immersion stress-, acetylsalicylic acid (ASA)- and histamine-induced erosions. In addition, ME3407 showed marked therapeutic effect on HCl- and ASA-induced lesions. In the lumen-perfused rats, oral administration of ME3407 inhibited dose-dependently (1-100 mg/kg) gastric acid secretion induced by histamine and tetragastrin with ED50 values of 3.02 and 3.37 mg/kg, respectively. Oral administration of ME3407 at a dose of 30 mg/kg also inhibited the elevation of serum gastrin level. The development of duodenal ulcers caused by mepirizole and systeamine was also potently inhibited by ME3407 at an oral dose of 0.1-30 mg/kg. However, when given at 30 mg/kg intraduodenally, subcutaneously or intravenously, ME3407 did not inhibit these acutely induced gastric elosion and acid output. ME3407 was not detected in the serum upon oral administration. These results indicated that ME3407 was active only by oral administration, and exerts direct action on the ulcers and acid secretion from the gastric membrane.
Tanaka
Junko
J
Pharmacology Department, Drug Research Laboratories, Pharmaceutical Research Center, Meiji Seika Kaisha, Ltd., Yokohama, Japan. junko_tanaka@meiji.co.jp
Iida
Hiroyuki
H
Abe
Mitsuhiro
M
Yuda
Yasukatu
Y
Inoue
Shigeharu
S
Okabe
Susumu
S
D000818:Animals; D000893:Anti-Inflammatory Agents; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D001241:Aspirin; D001562:Benzimidazoles / Q000494:pharmacology*; D003543:Cysteamine; D004381:Duodenal Ulcer / Q000139:chemically induced / Q000517:prevention & control; D004840:Epirizole; D005744:Gastric Acid / Q000378:metabolism*; D005747:Gastric Fistula / Q000503:physiopathology; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism*; D005755:Gastrins / Q000097:blood; D006632:Histamine; D007101:Immersion / Q000009:adverse effects; D007213:Indomethacin; D008297:Male; D010434:Pepsin A / Q000378:metabolism; D011708:Pylorus / Q000502:physiology; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D013276:Stomach Ulcer / Q000139:chemically induced / Q000517:prevention & control; D013844:Thiazoles / Q000494:pharmacology*
D000893:Anti-Inflammatory Agents; D000897:Anti-Ulcer Agents; D001562:Benzimidazoles; D005755:Gastrins; C106473:ME 3407; D011725:Pyridines; D013844:Thiazoles; D004840:Epirizole; D003543:Cysteamine; D006632:Histamine; D010434:Pepsin A; D001241:Aspirin; D007213:Indomethacin