Effects of the novel histamine H2-receptor antagonist (+/-)-(E)-1-[2-hydroxy-2-(4-hydroxyphenyl)ethyl]-3-[2-[[[5- (methylamino)methyl-2-furyl]methyl]thio]ethyl]-2-(methylsulfonyl) guanidine on gastric secretion and gastroduodenal ulcers in rats.
The effects of (+/-)-(E)-1-[2-hydroxy-2-(4-hydroxyphenyl)ethyl]-3-[2- [[[5-(methylamino)methyl-2-furyl] methyl]thio]ethyl]-2-(methylsulfonyl)guanidine (CAS 140695-21-2, T-593), a new histamine H2-receptor antagonist, on gastric secretion and experimental gastric and duodenal lesion/ulcer models in rats were examined. The drug administered orally or intraduodenally significantly and dose-dependently inhibited both basal and histamine-stimulated acid secretion. Pepsin output was also inhibited by the drug nearly dose-dependently. The acid-inhibitory effect of T-593 persisted for 12 h after a single oral administration. T-593 potently protected the gastric mucosa against water-immersion stress-, indometacin- and HCl.acetylsalicylic acid-induced lesions, but it had no effect on HCl.ethanol-induced lesions. T-593 significantly prevented the development of mepirizole-induced duodenal ulcers. Spontaneous healing of kissing gastric ulcers was significantly enhanced when T-593 was administered for 14 days. The antisecretory and antilesion/antiulcer effects of T-593 were similar to those of ranitidine and omeprazole. It is concluded that T-593 is a potent antisecretory and antiulcer drug.
Amagase
K
K
Department of Applied Pharmacology, Kyoto Pharmaceutical University, Japan.
Kato
S
S
Yamamoto
H
H
Okabe
S
S
D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004840:Epirizole; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism*; D006146:Guanidines / Q000494:pharmacology* / Q000627:therapeutic use; D006632:Histamine / Q000494:pharmacology; D006635:Histamine H2 Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D007213:Indomethacin; D008297:Male; D009853:Omeprazole / Q000494:pharmacology / Q000627:therapeutic use; D010434:Pepsin A / Q000378:metabolism; D010437:Peptic Ulcer / Q000139:chemically induced / Q000188:drug therapy* / Q000209:etiology; D011899:Ranitidine / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D013276:Stomach Ulcer / Q000139:chemically induced / Q000517:prevention & control; D013315:Stress, Psychological / Q000150:complications; D013450:Sulfones / Q000494:pharmacology* / Q000627:therapeutic use
D000897:Anti-Ulcer Agents; D006146:Guanidines; D006635:Histamine H2 Antagonists; D013450:Sulfones; C088837:T 593; D004840:Epirizole; D006632:Histamine; D011899:Ranitidine; D010434:Pepsin A; D009853:Omeprazole; D007213:Indomethacin