Sekiguchi H, Hamada K, Taga F, Nishino K
Central Research Laboratories, Kyorin Pharmaceutical Co., Ltd., Tochigi, Japan.
Arzneimittelforschung. 1993 Feb;43(2):134-8.
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.
将KU-1257（N-乙基-N'-[3-[3-(哌啶甲基)苯氧基]丙基]脲，CAS 120958-90-9）对大鼠胃损伤和十二指肠溃疡的影响与各种抗溃疡药物进行了比较。KU-1257可预防坏死剂诱导的胃损伤形成。对0.6 N盐酸诱导的胃损伤的半数有效剂量（ID50）经口给药为18.6 mg/kg，腹腔注射为6.0 mg/kg。对无水乙醇和1%氨水诱导的胃损伤的ID50经口给药分别为12.4和9.2 mg/kg。醋酸罗沙替丁、曲昔匹特和替普瑞酮经口给药剂量为100 - 200 mg/kg时也能显著预防这些坏死剂诱导的胃损伤形成。西咪替丁、雷尼替丁和法莫替丁即使经口给药剂量为200 mg/kg对这些胃损伤也没有保护作用。KU-1257、醋酸罗沙替丁和法莫替丁可抑制乙酰水杨酸和水浸应激诱导的胃损伤。KU-1257、醋酸罗沙替丁和法莫替丁可抑制美吡立唑诱导的十二指肠溃疡，但曲昔匹特和替普瑞酮则不能。这些结果表明，KU-1257在黏膜保护作用方面比曲昔匹特、替普瑞酮、醋酸罗沙替丁和其他组胺H2受体拮抗剂更强。
