EFFECTS OF THE NEW HISTAMINE H-2-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-(piper-idinomethyl)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, po. and 6.0 mg/kg, ip. The ID50 values against absolute ethanol-and 1 % NH3-induced gastric lesions were 12.4 and 9.2 mg/kg, po., 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 H-2-receptor antagonists.