Examination of the potential antiulcer activity of the calcium antagonist propyl-methylenedioxyindene. III. Lack of effect on cysteamine-induced duodenal ulcers in rats.
Since propyl-methylenedioxyindene (pr-MDI) exhibits significant protective effects against stress-induced ulcers in rats at subcardiovascular doses (10-30 mg/kg, i.p.), the aim of the present study was to explore the effect of this intracellular calcium antagonist on cysteamine-induced duodenal ulcers at the same low doses. Duodenal ulcers were induced in rats with a single dose of cysteamine (425 mg/kg, s.c.), which produced an 80% ulcer incidence within 24 h without affecting gastric acid concentration. Administration of pr-MDI (10 and 30 mg/kg, i.p.) at 0, 6 and 12 h post-cysteamine did not afford protection against ulceration. On the other hand, atropine (10 mg/kg, s.c., administered at 0, 6 and 12 h post-cysteamine) resulted in a 69% inhibition of ulceration, and the antacid Maalox (2 ml, administered p.o. at 0, 2, 4, 6 and 12 h post-cysteamine) completely prevented ulceration. The failure of pr-MDI to protect against duodenal ulceration is discussed in relation to its pharmacological mechanism of action and the pathogenetic mechanism of action of cysteamine.
Wong
W S
WS
Division of Pharmacology, College of Pharmacy, Ohio State University, Columbus.
Rahwan
R G
RG
Stephens
R L
RL
D000536:Aluminum Hydroxide / Q000494:pharmacology; D000818:Animals; D000863:Antacids / Q000494:pharmacology; D000897:Anti-Ulcer Agents; D001285:Atropine / Q000494:pharmacology; D001626:Bethanechol Compounds / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003543:Cysteamine; D004298:Dopamine / Q000494:pharmacology; D004338:Drug Combinations; D004381:Duodenal Ulcer / Q000139:chemically induced / Q000517:prevention & control*; D005260:Female; D005744:Gastric Acid / Q000378:metabolism; D005769:Gastrointestinal Motility / Q000187:drug effects; D007192:Indenes / Q000494:pharmacology*; D008276:Magnesium Hydroxide / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013276:Stomach Ulcer / Q000139:chemically induced / Q000517:prevention & control; D014700:Verapamil / Q000494:pharmacology
D000863:Antacids; D000897:Anti-Ulcer Agents; D001626:Bethanechol Compounds; D002121:Calcium Channel Blockers; D004338:Drug Combinations; D007192:Indenes; C013591:aluminum hydroxide, magnesium hydroxide, drug combination; D000536:Aluminum Hydroxide; D003543:Cysteamine; D001285:Atropine; C064266:propylmethylenedioxyindene; D014700:Verapamil; D008276:Magnesium Hydroxide; D004298:Dopamine