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新型组胺H2受体拮抗剂N-乙基-N'-[3-[3-(哌啶甲基)苯氧基]丙基]脲对大鼠乙酸诱导的慢性胃溃疡和十二指肠溃疡的双重促愈合作用

Healing-promoting action of the new histamine H2-receptor antagonist N-ethyl-N'-[3-[3-(piperidinomethyl)phenoxy]propyl]urea with dual action on chronic gastric and duodenal ulcers induced by acetic acid in rats.

作者信息

Sekiguchi H, Hamada K, Aijima H, Taga F, Uchida H, Nishino K

机构信息

Central Research Laboratories, Kyorin Pharmaceutical Co., Ltd, Tochigi, Japan.

出版信息

Arzneimittelforschung. 1993 Feb;43(2):139-43.

PMID:8096134
Abstract

Healing-promoting actions of KU-1257 (N-ethyl-N'-[3-[3-(piperidinomethyl)phenoxy]propyl]urea, CAS 120958-90-9) were investigated in chronic gastric and duodenal ulcer models induced by acetic acid in rats and the effects were compared with those of famotidine and roxatidine acetate by gross or histological evaluation. KU-1257 markedly promoted the well-balanced healing of gastric ulcer at oral doses of 10-50 mg/kg x 2/day, as evidenced by the reduction of ulcer, regeneration of mucosa and proliferation of connective tissue. KU-1257 caused an increase in gastric mucus secretion in the regenerated mucosa around the gastric ulcers. Famotidine and roxatidine acetate failed to promote the healing of gastric ulcers even at 100 mg/kg x 2/day p.o. KU-1257 also significantly accelerated the healing of acetic acid-induced duodenal ulcers as well as famotidine and roxatidine acetate. These results indicate that KU-1257 is characterized by a potent promoting action on the healing of chronic ulcers, suggesting that the increase in gastric mucus secretion might be associated with the antiulcer actions of KU-1257 in part.

摘要

在大鼠乙酸诱导的慢性胃溃疡和十二指肠溃疡模型中研究了KU-1257(N-乙基-N'-[3-[3-(哌啶甲基)苯氧基]丙基]脲,CAS 120958-90-9)的促愈合作用,并通过大体或组织学评估将其与法莫替丁和醋酸罗沙替丁的作用进行比较。口服剂量为10-50mg/kg×2/天的KU-1257显著促进胃溃疡的均衡愈合,表现为溃疡缩小、黏膜再生和结缔组织增生。KU-1257使胃溃疡周围再生黏膜中的胃黏液分泌增加。即使口服剂量为100mg/kg×2/天,法莫替丁和醋酸罗沙替丁也未能促进胃溃疡的愈合。KU-1257还显著加速了乙酸诱导的十二指肠溃疡的愈合,法莫替丁和醋酸罗沙替丁也有此作用。这些结果表明,KU-1257的特点是对慢性溃疡的愈合有强大的促进作用,提示胃黏液分泌增加可能部分与KU-1257的抗溃疡作用有关。

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