Effect of a novel xanthine derivative on experimental ulcers in rats.
The effects of the novel xanthine derivative 3-ethyl-1-(6-hydroxy-6-methylheptyl)-7-propylxanthine (A90 6119, CAS 134072-58-5) on various experimentally induced ulcers was investigated in rats. A90 6119 produced a dose-dependent inhibition of gastric ulcers induced by water immersion stress and absolute ethanol with ED50- values of 2.4 and 2.8 mg/kg, p.o., respectively. The erosion induced by oral administration of 1.5% NH4OH (3 ml/rat) was significantly reduced by A90 6119 at 10 and 30 mg/kg, p.o. Likewise, A90 6119 caused a dose-dependent inhibition of gastric erosions and intestinal hemorrhage induced by platelet activating factor (PAF) with ED50- values of 8.7 and 11.9 mg/kg p.o., respectively. Duodenal ulcer induced by cysteamine was also dose-dependently inhibited by A90 6119 with an ED50-value of 0.3 mg/kg, i.p. When doses of cimetidine (200 mg/kg) and A90 6119 (10 mg/kg), equipotent in the water immersion stress model, were orally given twice daily for 5 consecutive days before the induction of gastric ulcers by stress, the H2-receptor antagonist aggravated significantly the ulcer formation while the xanthine derivative did not show such an effect. These data suggest that the 3-ethylxanthine A90 6119 possesses pronounced anti-ulcer activity and that its repeated administration might not aggravate ulcer formation and might reduce the incidence of recurrence.
Tanaka
T
T
Laboratory for Pharmacology, Hoechst Japan Ltd. Saitama.
Morioka
Y
Y
Gebert
U
U
D064753:Ammonium Hydroxide; D000818:Animals; D000897:Anti-Ulcer Agents / Q000627:therapeutic use*; D003080:Cold Temperature; D003543:Cysteamine; D004381:Duodenal Ulcer / Q000139:chemically induced / Q000517:prevention & control; D000431:Ethanol; D006878:Hydroxides; D007101:Immersion; D008297:Male; D010437:Peptic Ulcer / Q000139:chemically induced / Q000209:etiology / Q000517:prevention & control*; D010438:Peptic Ulcer Hemorrhage / Q000517:prevention & control; D010972:Platelet Activating Factor; D051381:Rats; D017207:Rats, Sprague-Dawley; D013276:Stomach Ulcer / Q000139:chemically induced / Q000517:prevention & control; D013315:Stress, Psychological / Q000150:complications; D014970:Xanthines / Q000627:therapeutic use*
D000897:Anti-Ulcer Agents; D006878:Hydroxides; D010972:Platelet Activating Factor; D014970:Xanthines; C082076:3-ethyl-1-(6-hydroxy-6-methylheptyl)-7-propylxanthine; D000431:Ethanol; D064753:Ammonium Hydroxide; D003543:Cysteamine