Effects of the new histamine H2-receptor antagonist N-ethyl-N'-[3-[3-(piperidinomethyl)phenoxy]propyl] urea with potent gastric mucosal protective activity on acute gastric lesions and duodenal ulcers in rats.
The effects of KU-1257 (N-ethyl-N'-[3-[3-(piperidinomethyl)phenoxy]propyl]urea, CAS 120958-90-9) on gastric lesions and duodenal ulcers in rats were compared with those of various antiulcer drugs. KU-1257 prevented the formation of gastric lesions induced by necrotizing agents. The ID50 values against 0.6 N HCl-induced gastric lesions were 18.6 mg/kg, p.o. and 6.0 mg/kg, i.p. The ID50 values against absolute ethanol- and 1% NH3-induced gastric lesions were 12.4 and 9.2 mg/kg, p.o., respectively. Roxatidine acetate, troxipide and teprenone at doses of 100-200 mg/kg p.o. also significantly prevented the formation of gastric lesions by these necrotizing agents. Cimetidine, ranitidine and famotidine had no protective effect against these gastric lesions even at a dose of 200 mg/kg p.o. KU-1257, roxatidine acetate and famotidine inhibited acetylsalicylic acid- and water-immersion stress-induced gastric lesions. KU-1257, roxatidine acetate and famotidine inhibited mepirizole-induced duodenal ulcers, but not troxipide and teprenone. These results suggest that KU-1257 is more potent in the mucosal protective action than troxipide, teprenone, roxatidine acetate and other histamine H2-receptor antagonists.
Sekiguchi
H
H
Central Research Laboratories, Kyorin Pharmaceutical Co., Ltd., Tochigi, Japan.
Hamada
K
K
Taga
F
F
Nishino
K
K
D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D001241:Aspirin; D003486:Cyanides; D004381:Duodenal Ulcer / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D004840:Epirizole; D000431:Ethanol; D005753:Gastric Mucosa / Q000187:drug effects* / Q000473:pathology; D006635:Histamine H2 Antagonists / Q000494:pharmacology*; D006851:Hydrochloric Acid; D007101:Immersion; D007413:Intestinal Mucosa / Q000473:pathology; D008297:Male; D010671:Phenylurea Compounds / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013276:Stomach Ulcer / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D013315:Stress, Psychological / Q000150:complications
D000897:Anti-Ulcer Agents; D003486:Cyanides; D006635:Histamine H2 Antagonists; D010671:Phenylurea Compounds; D010880:Piperidines; C080362:KU 1257; D004840:Epirizole; D000431:Ethanol; D006851:Hydrochloric Acid; D001241:Aspirin