Anti-ulcerogenic effects of
trimoprostil, a
prostaglandin E2 (
PGE2) derivative, were studied in comparison with those of
PGE2,
cimetidine and
sulpiride.
Trimoprostil and
PGE2 given p.o. prevented the formation of gastric lesions produced by absolute
ethanol, 0.2N NaOH, 0.6N HCI and hypertonic NaCl solutions in rats and
aspirin-induced fecal occult
bleeding in dogs. Although both
prostaglandins did not alter the gastric mucus content, they equivalently prevented the stress-induced decrease in the mucus content in rats. The duration of these effects of
trimoprostil was longer than those of
PGE2.
Cimetidine and
sulpiride did not exert such cytoprotective effects.
Trimoprostil inhibited stress-induced
gastric ulcer formation in rats more markedly than
PGE2,
cimetidine and
sulpiride.
Trimoprostil and
PGE2 at the cytoprotective dose (30 micrograms/kg, p.o.) did not change the gastric blood flow in conscious rats. In Shay rats,
trimoprostil at doses larger than the cytoprotective doses inhibited the gastric acid secretion when given p.o., but was not effective when given i.d.
PGE2 exerted the similar action, but the potency was clearly weaker than that of
trimoprostil. In Heidenhain-pouch dogs,
trimoprostil also inhibited the gastric acid secretion stimulated by
pentagastrin more markedly than did
cimetidine. In conclusion,
trimoprostil at doses smaller than the antisecretory doses exerted gastric cytoprotective action with a longer duration than that of
PGE2, probably through the preservation of the mucus barrier. Such cytoprotection was not found with
cimetidine and
sulpiride.