[Effect of AS-2646, a novel antiulcer agent on gastric mucosal defensive factors in rats].
The effects of AS-2646 on the acute gastric mucosal lesions induced by various noxious agents and the gastric mucosal defensive factors were studied in rats, and the following results were obtained: 1) AS-2646 (5-100 mg/kg, p.o.) dose-dependently inhibited the formation of the mucosal lesions induced by ethanol, ethanol-HCl, taurocholate-HCl and serotonin, and its anti-lesion spectrum was the widest among the compounds (cimetidine, pirenzepine, sulpiride and prostaglandin E1) examined here. 2) AS-2646 (5-10 mg/kg, p.o.) not only improved the changes of gastric mucosal hemodynamics induced by the blood removal and/or the reserpine treatment, but also inhibited the mucosal lesions induced by them. 3) AS-2646 (2-20 mg/kg, p.o.) antagonized the decrease in the surface gastric mucus and mucosal hexosamine contents induced by stress and/or aspirin. 4) AS-2646 (2-20 mg/kg, p.o.) caused no significant effect on the gastric mucosal prostaglandin E2 levels. 5) AS-2646 inhibited Campylobacter pylori in vitro. These results indicate that AS-2646 may be useful as a novel antiulcer drug with the defensive factor-potentiating and anti-Campylobacter pylori effects.
Department of Pharmacology, Dainippon Pharmaceutical Co., Ltd., Osaka, Japan.
K
K
Kawashima
K
K
Kondoh
Y
Y
Ochi
M
M
Oka
D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology* / Q000627:therapeutic use; D015232:Dinoprostone / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004352:Drug Resistance, Microbial; D005750:Gastric Juice / Q000378:metabolism; D005753:Gastric Mucosa / Q000098:blood supply / Q000378:metabolism; D016480:Helicobacter pylori / Q000187:drug effects; D006595:Hexosamines / Q000378:metabolism; D008297:Male; D011804:Quinolines / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D011919:Rats, Inbred Strains; D012039:Regional Blood Flow / Q000187:drug effects; D012701:Serotonin; D013276:Stomach Ulcer / Q000139:chemically induced / Q000188:drug therapy*
D000897:Anti-Ulcer Agents; D006595:Hexosamines; D011804:Quinolines; D012701:Serotonin; C026400:AD 1308; D015232:Dinoprostone