Spizofurone (AG-629) increases gastric mucosal blood flow in dogs: a possible mechanism of its anti-ulcer effect.
The effect of spizofurone (AG-629), a new anti-ulcer agent, on gastric mucosal blood flow was investigated in anesthetized dogs and the effects were compared with those of prostaglandin E2. Intravenous administration of spizofurone in doses of 15 and 30 mg/kg caused a dose-related increase in gastric mucosal blood flow. Spizofurone (1-10 mg/ml) given intragastrically for 15 min produced a sustained increase in gastric mucosal blood flow in a concentration-dependent manner; with 3 mg/ml there was about a 50% increase in gastric mucosal blood flow at the peak and a 2 h duration of action. The mode of action of spizofurone was similar to that of prostaglandin E2. The reduction in the gastric mucosal blood flow as induced by indomethacin was markedly improved by spizofurone. The topical action of spizofurone was confirmed in an in situ experiment using a stomach flap fixed to a lucite chamber. These results indicate that spizofurone increases gastric mucosal blood flow after systemic and topical administration, and this increase in gastric mucosal blood flow would account for the anti-ulcer effects of this drug.
D000632:Aminopyrine / Q000378:metabolism; D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D001572:Benzofurans / Q000494:pharmacology*; D015237:Dinoprost; D015232:Dinoprostone; D004285:Dogs; D005260:Female; D005753:Gastric Mucosa / Q000098:blood supply*; D006859:Hydrogen / Q000378:metabolism; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D011458:Prostaglandins E / Q000494:pharmacology; D011460:Prostaglandins F / Q000494:pharmacology; D012039:Regional Blood Flow / Q000187:drug effects; D013997:Time Factors
D000897:Anti-Ulcer Agents; D001572:Benzofurans; D011458:Prostaglandins E; D011460:Prostaglandins F; D000632:Aminopyrine; D006859:Hydrogen; C045902:spizofurone; D015237:Dinoprost; D015232:Dinoprostone; D007545:Isoproterenol; D007213:Indomethacin