Gastric cytoprotective, antisecretory and antiulcer activities of (E)-4-oxo-4-(3,4,5-trimethoxyphenyl)-2-butenoic acid (RU 38086).

As a result of trials of a large series of compounds, RU 38086 (E)-4-oxo-4-(3,4,5-trimethoxyphenyl)-2-butenoic acid) was selected because of its cytoprotective, antisecretory and antiulcer properties. In pylorus-ligated rats, RU 38086 dose-dependently decreased the total acid output, at 2.5, 5 and 10 mg/kg orally and at 10 and 50 mg/kg intraduodenally. In the perfused rat stomach, 1.2 mg/kg RU 38086 in situ inhibited acid secretion stimulated by histamine or pentagastrin but was inactive against carbachol. In the same test 5 mg/kg intravenously did not antagonize pentagastrin-induced acid secretion. In the cat Heidenhain pouch, 0.6 mg/kg RU 38086 was also antisecretory, reducing the acid concentration when in contact with the mucosa of the pouch. In ulcers induced in rats by ligature of the pylorus plus acetylsalicylic acid, RU 38086 at 2.5 and 5 mg/kg demonstrated much more striking activity after oral than after intraduodenal administration. It also had antiulcer activity against stress ulcers (restraint plus cold), starting at a dose of 5 mg/kg orally. RU 38086 had marked gastric cytoprotective activity in rats against the necrotizing effects of ethanol from the low dose of 0.3 mg/kg orally. This cytoprotective activity was not significantly affected by indomethacin pre-treatment. At 4 and 20 mg/kg orally, RU 38086 strongly increased prostaglandin E2 levels in gastric juice of pylorus-ligated rats and in stomach tissue of normal rats. These data indicate that RU 38086 is an orally effective cytoprotective, antisecretory and antiulcer agent.