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.