Effects of the novel anti-ulcer agent 1-(5'-oxohexyl)-3-methyl-7-propyl xanthine on experimental ulcers and gastric secretion in rats.

Abstract

The effects of 1-(5'-oxohexyl)-3-methyl-7-propyl xanthine (HWA 285) on various experimentally induced ulcers and gastric acid secretion were investigated in rats. HWA 285 (10-50 mg/kg, p.o.) inhibited restraint and water-immersion-induced stress, ulcers, indometacin- and absolute ethanol-induced gastric ulcers and mepirizole-induced duodenal ulcers in rats in a dose-dependent manner. HWA 285 (10-25 mg/kg i.d.) had inhibitory effects on acetylsalicylic acid-induced ulcers. The healing of acetic acid-induced chronic ulcers was significantly accelerated by HWA 285 (25 mg/kg p.o.) when it was given twice daily for 7 consecutive days. When given orally (twice a day, 11 doses in total) before the induction of gastric ulcers by stress, cimetidine at 100 mg/kg aggravated the ulcers, whereas, HWA 285 at 25 mg/kg had not such an effect. In conscious pylorus-ligated rats, HWA 285 (10-100 mg/kg i.p.) showed a dose-dependent inhibition on basal and desglugastrin- and 2-deoxy-D-glucose (2-DG)-stimulated gastric acid secretion. In stomach-lumen perfused rats, HWA 285 (30 mg/kg i.v.) inhibited 2-DG-stimulated gastric acid secretion but not carbachol-stimulated gastric acid secretion. These results suggest that the anti-ulcer effects of HWA 285 are produced by cytoprotective and central anti-secretory activity without peripheral anti-cholinergic properties. Whether the central anti-secretory effects of HWA 285 play thereby the key role, have to be clarified in further investigation.

• Authors: T Tanaka, M Bickel, A W Herling, M Sakurai, M Goto, S Hayashi
• Journal: Arzneimittel-Forschung (Arzneimittelforschung) Vol. 39 Issue 6 Pg. 689-94 (Jun 1989) ISSN: 0004-4172 [Print] Germany
• PMID: 2775336 (Publication Type: Journal Article)

Chemical References

• Acetates
• Anti-Ulcer Agents
• Xanthines
• Epirizole
• Ethanol
• propentofylline
• Aspirin
• Indomethacin

Topics

• Acetates
• Animals
• Anti-Ulcer Agents (pharmacology)
• Aspirin
• Epirizole
• Ethanol
• Gastric Acid (metabolism)
• Gastric Mucosa (drug effects, metabolism)
• Immersion
• Indomethacin
• Male
• Perfusion
• Pylorus (physiology)
• Rats
• Rats, Inbred Strains
• Stomach Ulcer (chemically induced, drug therapy)
• Stress, Psychological (physiopathology)
• Xanthines (pharmacology)