Animal experiment:

Male Charles River CD rats weighing 140 and 200 g are fasted overnight with water ad lib. The rats are pretreated orally with compound (MK-447) or buffered glycol vehicle in a dosage volume of 1.0 mL/kg one hour before challenge with the necrotizing agents. The necrotizing agents [acetylsalicyclic acid at 40 suspended in 0.5% methylcellulose (1500 cps) or 37.5% ethanol] are administered p.o. in a dose volume of 0.1 mL/100 g body weight or 1 mL/rat, respectively. Rats are killed with CO2 one hour after acetylsalicylic acid or ethanol, the stomach removed, inflated with water, and opened ture. The presence of mucosal bleeding is noted and the mucosa is wiped off[1].

MK-447 is a free radical scavenger, also a nonsteroidal antiinflammatory agent, and enhances the formation of the endoperoxide, PGH2, and other prostaglandins.

MK-447 is a free radical scavenger, reduces the accumulation of the endoperoxide, PGG2 and also enhances the formation of the endoperoxide, PGH2, and other prostaglandins[1]. MK-447 (100 μM) increases the amounts of prostaglandin I2 (PGI2). MK-447 also accelerates endogenous PGI2 generation in the isolated rat aorta[2].

MK-447 (20 and 50 mg/kg, p.o.) blocks gastric acid secretion in the 4 hour pylorus ligated rats, but shows no effect on gastric secretion of pepsin. MK-447 (5, 10, 20 and 40 mg/kg, p.o.) dose-dependently decreases acid output in dogs[1].

[1]. Shriver DA, et al. The gastric antisecretory and antiulcer activity of MK-447, an enhancer of prostaglandin synthesis. Life Sci. 1980 Dec 22-29;27(25-26):2483-7. [2]. Harada Y, et al. Acceleration of endogeneous PGI2 generation from isolated rat aortae by MK-447. Jpn J Pharmacol. 1981 Oct;31(5):845-8.