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.
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.
Sekiguchi
H
H
Central Research Laboratories, Kyorin Pharmaceutical Co., Ltd, Tochigi, Japan.
Hamada
K
K
Aijima
H
H
Taga
F
F
Uchida
H
H
Nishino
K
K
D000085:Acetates; D000818:Animals; D000897:Anti-Ulcer Agents / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004381:Duodenal Ulcer / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D015738:Famotidine / Q000627:therapeutic use; D005753:Gastric Mucosa / Q000473:pathology; D006635:Histamine H2 Antagonists / Q000627:therapeutic use*; D007413:Intestinal Mucosa / Q000473:pathology; D008297:Male; D010671:Phenylurea Compounds / Q000627:therapeutic use*; D010880:Piperidines / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D013276:Stomach Ulcer / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology
D000085:Acetates; D000897:Anti-Ulcer Agents; D006635:Histamine H2 Antagonists; D010671:Phenylurea Compounds; D010880:Piperidines; C080362:KU 1257; D015738:Famotidine; C053742:roxatidine acetate