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.
Wong
W S
WS
Division of Pharmacology, Ohio State University, Columbus 43210.
Rahwan
R G
RG
D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D001626:Bethanechol Compounds / Q000494:pharmacology; D002927:Cimetidine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005744:Gastric Acid / Q000378:metabolism*; D005746:Gastric Emptying / Q000187:drug effects*; D007192:Indenes / Q000494:pharmacology*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D014700:Verapamil / Q000494:pharmacology
D000897:Anti-Ulcer Agents; D001626:Bethanechol Compounds; D007192:Indenes; D002927:Cimetidine; C064266:propylmethylenedioxyindene; D014700:Verapamil