1,6-dihydro-2-[2-(2-methylpropoxy)anilino]-6-oxo-5-pyrimidinecarbo xylic
acid, (MAR-99, CAS 98772-05-5) (10-30 mg/kg i.g.) improved the reduction of gastric blood flow rate induced by the administration of 99.5%
ethanol or acidified-
acetylsalicylic acid (ASA). In addition,
MAR-99 (3 x 10(-6)-3 x 10(-5) mol/l) protected dose-dependently the damage of epithelial cells induced by ulcerogenic agents such as
ethanol or acidified-ASA.
MAR-99 (1-10 mg/kg p.o.) prevented dose-dependently the reduction of
hexosamine content in glandular stomach. Furthermore,
MAR-99 (10-30 mg/kg i.g.) improved the decrease in gastric potential difference induced by 99.5%
ethanol and acidified-ASA.
MAR-99 (10-30 mg/kg p.o.) significantly inhibited the lesion formation induced by 99.5%
ethanol and such effect of this compound was not attenuated by the pretreatment with
indomethacin. Furthermore
MAR-99 (10 and 30 mg/kg p.o.) had no effect on the
prostaglandins (
PGE2 and I2) contents in the stomach of normal rats. In pylorus-ligated rats,
MAR-99 (3-100 mg/kg i.d.) showed a weak or no effect on acidity and
pepsin activity in gastric juice, although this compound decreased dose-dependently the volume of gastric juice. In perfused stomachs,
MAR-99 (30-100 mg/kg i.d.) slightly prevented the
acid secretion induced by
carbachol and
pentagastrin. However,
MAR-99 did not affect the
acid secretion stimulated by
histamine. These results indicated that anti-
ulcer effect of
MAR-99 was mainly due to maintenance of the gastric mucosal resistance.