Gastric antisecretory and cytoprotective activities of SCH 28080.
SCH 28080 (2-methyl-8-(phenylmethoxy)imidazo[1,2-a]pyridine-3-acetonitrile) is a novel antiulcer agent which has both antisecretory and cytoprotective activities. The antisecretory ED50 values in the pylorus-ligated rat were 3.7 mg/kg p.o. and 2.8 mg/kg i.p., being 7 and 10 times more potent than cimetidine, respectively. In dogs, SCH 28080 was effective in inhibiting acid secretion stimulated by histamine (ED50 of 0.09 mg/kg i.v. and 4.4 mg/kg p.o.), dimaprit, pentagastrin, insulin and feeding. The cytoprotective activity of SCH 28080 was demonstrated by inhibition of ethanol-induced gastric lesions in a dose-dependent manner in rats (ED50:3.0 mg/kg p.o.). SCH 28080 was active in similar dose ranges (1-10 mg/kg) by both p.o. and i.v. routes of administration. This gastric cytoprotective activity was not affected by indomethacin pretreatment. Furthermore, the gastric potential difference was effectively sustained by SCH 28080 (3, 10 and 30 mg/kg p.o.) after intragastric ethanol. SCH 28080 (1-30 mg/kg p.o.) also inhibited gastric ulcers provoked by aspirin, aspirin + acid, indomethacin and stress (cold-restraint) in rats. The data support the concept that it is possible to have combined antisecretory and cytoprotectant actions in a single molecule which is not a prostaglandin.
D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology; D001241:Aspirin; D002927:Cimetidine / Q000494:pharmacology; D004285:Dogs; D000431:Ethanol; D005260:Female; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000187:drug effects* / Q000502:physiology; D006632:Histamine / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology*; D007213:Indomethacin; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D051381:Rats; D013276:Stomach Ulcer / Q000209:etiology / Q000517:prevention & control; D013312:Stress, Physiological / Q000150:complications
D000897:Anti-Ulcer Agents; D007093:Imidazoles; C035235:Sch 28080; D000431:Ethanol; D002927:Cimetidine; D006632:Histamine; D001241:Aspirin; D007213:Indomethacin