Effects of a gastric antisecretory-cytoprotectant 2-methyl-8-(phenylmethoxy)imidazo[1,2-a]pyridine-3-acetonitrile (Sch 28 080) on cysteamine, reserpine and stress ulcers in rats.
Prostaglandin E2 and carbenoxolone, putative cytoprotective agents, were tested in cysteamine, reserpine and stress ulcers in rats. In cysteamine-induced duodenal ulcer, PGE2 was inactive at 0.1 and 0.5 mg/kg p.o.; carbenoxolone at 100 mg/kg p.o. decreased the incidence but not the severity of the ulcer. PGE2 at 5.0 mg/kg p.o. and carbenoxolone at 300 mg/kg p.o. showed moderate effects, but the dosage also inhibited cysteamine-stimulated acid secretion. PGE2 (0.1 and 0.3 mg/kg p.o.) was inactive and carbenoxolone (100 and 300 mg/kg p.o.) further aggravated the gastric ulceration caused by reserpine or cold-restraint stress. In contrast, atropine (3 and 10 mg/kg p.o.) and cimetidine (30, 100 and 300 mg/kg p.o.) were active in all three ulcer models. But the results with cimetidine in stress ulcer were somewhat variable. 2-methyl-8-(phenylmethoxy) imidazo [1,2-a] pyridine-3-acetonitrile (Sch 28 080), a novel structure with both cytoprotective and antisecretory activity, was highly efficacious in cysteamine, reserpine and stress ulcers (1-30 mg/kg p.o.), which was presumably adequately accounted for by its potent antisecretory activity. It is concluded that cysteamine, reserpine and stress ulcers may not be appropriate models for testing the potential antiulcer effect of primarily cytoprotective compounds.
D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D001285:Atropine / Q000494:pharmacology; D002229:Carbenoxolone / Q000494:pharmacology; D003080:Cold Temperature; D003543:Cysteamine / Q000037:antagonists & inhibitors*; D015232:Dinoprostone; D005744:Gastric Acid / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D010437:Peptic Ulcer / Q000139:chemically induced / Q000209:etiology / Q000517:prevention & control*; D011458:Prostaglandins E / Q000494:pharmacology; D051381:Rats; D012110:Reserpine / Q000037:antagonists & inhibitors*; D012149:Restraint, Physical; D013312:Stress, Physiological / Q000150:complications*
D000897:Anti-Ulcer Agents; D007093:Imidazoles; D011458:Prostaglandins E; C035235:Sch 28080; D003543:Cysteamine; D001285:Atropine; D012110:Reserpine; D015232:Dinoprostone; D002229:Carbenoxolone