The gastric antisecretory and antiulcer activity of MK-447, an enhancer of prostaglandin synthesis

MK-447 is a free radical scavenger and in the arachidonic acid cascade it reduces the accumulation of the endoperoxide, PGG 2. It also enhances the formation of the endoperoxide, PGH 2, and other prostaglandins. Since many prostaglandins reduce gastric acid secretion and protect the gastric mucosa from gastric lesion formation induced by a number of agents, studies were commenced to determine if MK-447 possessed these prostaglandin-like activities. The results of these studies showed that MK-447 at doses of 20 and 50 mg/kg reduced acid secretion by 48.6 and 85.2%, respectively, in the 4 hr. pylorus ligated rat and that doses ranging from 12.5 to 50 mg/kg reduced gastric lesion formation induced by 37.5% ethanol or 40 mg/kg of aspirin in the rat. Additional studies in total gastric fistula dogs also showed that it reduced betazole stimulated acid secretion.