Antiulcer activity of the calcium antagonist propyl-methylenedioxyindene--II. Effects on acid secretion and gastric emptying in rats.

1. Propyl-methylenedioxyindene (pr-MDI) is an intracellularly acting calcium antagonist which protects against cold/restraint-induced stress ulcers in rats. The doses of pr-MDI which produce antiulcer activity (10-30 mg/kg i.p.) are significantly lower than those which exhibit cardiovascular effects. 2. Two potential mechanisms for the antiulcer action of pr-MDI were investigated in this study: the effects on hydrochloric acid secretion and on gastric motility (gastric emptying). 3. Bethanechol-induced hydrochloric acid secretion in acutely pylorus-ligated rats was significantly obtunded by pr-MDI (30 mg/kg i.p.), but the effect was significantly weaker than that produced by verapamil (16 mg/kg i.p.) or cimetidine (10 mg/kg i.p.). Since 30 mg/kg pr-MDI produces greater antiulcer activity than the very high dose of 16 mg/kg verapamil, it is unlikely that inhibition of acid secretion plays more than a contributory role in the antiulcer mechanism of action of pr-MDI. 4. pr-MDI (10-30 mg/kg i.p.) produced a dose-dependent slowing of gastric emptying in rats fed a methylcellulose/Phenol Red test meal, and this effect correlated well with the antiulcer action. Verapamil (16 mg/kg i.p.) did not affect gastric emptying. 5. The results indicate that a reduction of gastric motility plays a major role in the mechanism of the antiulcer action of pr-MDI.