Gastric cytoprotective properties of SCH 32651, a novel antiulcer agent.
The antisecretory activity of SCH 32651 (3-amino-2-methyl-8-phenylmethoxyimidazo[1,2-a] pyrazine HCl . 1/3 H2O) has been described in a preceding paper. This report describes its gastric cytoprotective properties. SCH 32651 inhibited the gastric lesions due to ethanol in a dose-dependent manner (ID50 = 5 mg/kg p.o.) and exerted its maximal effect when given 30 min before ethanol and had a duration of at least 90 min at 30 mg/kg p.o. The activity of SCH 32651 against ethanol was unaffected by indomethacin pretreatment. Furthermore, SCH 32651 produced significant increases in gastric mucus release (10-100 mg/kg p.o.) and rapidly reversed ethanol-induced (30-100 mg/kg p.o.) fall in gastric potential difference (PD). SCH 32651 displayed significant antiulcer activity in indomethacin-(30-100 mg/kg p.o.), aspirin - (30-100 mg/kg p.o.), "aspirin + acid" - (10-100 mg/kg p.o.), reserpine - (10-100 mg/kg p.o.), stress - (30-100 mg/kg p.o.), and cysteamine (10-100 mg/kg p.o.) ulcers. The present data in conjunction with those reported in a preceding paper indicate that SCH 32651 is an orally effective novel antiulcer drug with both gastric antisecretory and cytoprotective properties.
D000284:Administration, Oral; D000818:Animals; D001241:Aspirin / Q000009:adverse effects / Q000037:antagonists & inhibitors; D002927:Cimetidine / Q000627:therapeutic use; D003543:Cysteamine / Q000009:adverse effects / Q000037:antagonists & inhibitors; D004353:Drug Evaluation, Preclinical; D004381:Duodenal Ulcer / Q000139:chemically induced / Q000517:prevention & control; D000431:Ethanol / Q000009:adverse effects / Q000037:antagonists & inhibitors; D005753:Gastric Mucosa / Q000187:drug effects; D007093:Imidazoles / Q000627:therapeutic use*; D007213:Indomethacin / Q000009:adverse effects / Q000037:antagonists & inhibitors; D008297:Male; D011719:Pyrazines / Q000627:therapeutic use*; D051381:Rats; D012110:Reserpine / Q000009:adverse effects / Q000037:antagonists & inhibitors; D013276:Stomach Ulcer / Q000139:chemically induced / Q000517:prevention & control*; D013312:Stress, Physiological
D007093:Imidazoles; D011719:Pyrazines; D000431:Ethanol; D003543:Cysteamine; D002927:Cimetidine; C042837:3-amino-2-methyl-8-phenylmethoxyimidazo(1,2-a)pyrazine; D012110:Reserpine; D001241:Aspirin; D007213:Indomethacin