Antiulcer activity of the calcium antagonist propyl-methylenedioxyindene--I. Effect on cold/restraint stress-induced ulcers in rats.
1. Propyl-methylenedioxyindene (pr-MDI) is an intracellularly acting calcium antagonist with H2-receptor blocking properties. Stimulus-secretion coupling is inhibited by much lower concentrations of pr-MDI than is excitation-contraction coupling. 2. Since the processes leading to gastric ulceration are calcium-dependent, the aim of this study was to determine if pr-MDI could provide useful antiulcer activity at doses below those required to produce cardiovascular effects. 3. The antiulcer activity of pr-MDI (10-30 mg/kg) was examined in the cold (4 degree C)/restraint (3 hr) stress-induced ulcer model in male rats, and compared with the effects of the H2-blocker cimetidine (10-30 mg/kg) and the calcium channel blocker verapamil (11-32 mg/kg). The drugs were administered intraperitoneally 10 min prior to the cold/restraint stress. 4. All three drugs significantly reduced the number of ulcers and the cumulative length of ulcerated stomach surface in a roughly dose-dependent and equivalent manner. However, whereas the antiulcer doses of verapamil were extremely high, those of pr-MDI were one-sixth to one-half of its antiarrhythmic ED50 in rodents.
Wong
W S
WS
Division of Pharmacology, Ohio State University, Columbus 43210.
Rahwan
R G
RG
D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D002927:Cimetidine / Q000494:pharmacology; D003080:Cold Temperature; D004305:Dose-Response Relationship, Drug; D005753:Gastric Mucosa / Q000473:pathology; D007192:Indenes / Q000494:pharmacology*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012149:Restraint, Physical; D013276:Stomach Ulcer / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D013312:Stress, Physiological / Q000150:complications; D014700:Verapamil / Q000494:pharmacology
D000897:Anti-Ulcer Agents; D007192:Indenes; D002927:Cimetidine; C064266:propylmethylenedioxyindene; D014700:Verapamil