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The synthetic prostaglandin, SC-46275, an omega chain cyclopentenyl analog of enisoprost, was studied to determine its gastric antisecretory potency and duration of action in meal-stimulated innervated (Pavlov) pouch dogs and its p.o. bioavailability in unoperated fasted dogs. SC-46275 exhibited potent antisecretory activity when administered directly into the gastric pouch, the ED50 being 0.01 micrograms/kg. It had a long duration of antisecretory action; significant (P less than or equal to .05) inhibition of total acid output was observed 16 hr after intrapouch administration of 0.03 micrograms/kg. At this dose p.o., neither SC-46275 nor its free acid metabolite was detected in plasma. These data indicate that SC-46275 has novel properties: it is a potent, long-acting gastric antisecretory agent which is not readily available systemically after p.o. administration. Thus, potential systemic side effects are expected to be absent or minimized at doses of SC-46275 which inhibit gastric acid secretion, and therefore it might be useful in peptic ulcer disease.

The beneficial antiulcer actions of carbenoxolone may possibly be due to an aldosterone-like component on the gastric mucosa. This suggests that aldosterone and possibly other corticoids may have antiulcer actions. The potential gastric antisecretory and antiulcer actions of aldosterone (ALDO) and desoxycorticosterone acetate (DOCA) were studied in the rat in comparison to the reference standard carbenoxolone. Stress ulcers were induced in fasted rats by the the forced exertion technique. Gastric secretion was evaluated in the five-hour pyloric ligated Shay rat model. The renal mineralocorticoid actions of these drugs were also studied in the adrenalectomized rat. Intragastric administration of carbenoxolone and DOCA, but not ALDO, significantly inhibited gastric ulcer formation in rats. Carbenoxolone given subcutaneously (s.c.) did not inhibit ulcer formation. ALDO exhibited antiulcer actions only when multiple s.c. injections were made. The antiulcer actions of DOCA and ALDO are not mediated via an inhibitory effect on gastric secretion. At all doses tested DOCA and ALDO showed significant renal effect, while carbenoxolone exhibited this effect only at the highest tested dose. These results suggest that the beneficial antiulcerogenic action of carbenoxolone is due to a direct effect on gastric mucosa and is not related to an aldosterone-like component.