title: Protective action of SCH 12223 against experimentally induced gastric and intestinal lesions.
abstract: The gastrointestinal protective action of SCH 12223 [3-(n-butyl)-4-hydroxy-1-phenyl-1,8-naphthyridin-2(1H)-one hydrate, sodium salt] against various noxious stimuli was characterized in rats. SCH 12223 inhibited the ethanol-induced gastric lesions when given p.o. (0.3-3 mg/kg) or i.v. (1 and 3 mg/kg). Indomethacin pretreatment (10 mg/kg p.o.) did not interfere with this effect. SCH 12223 was also active p.o. in five gastric erosion models: aspirin (1-10 mg/kg), aspirin + acid (1-30 mg/kg), indomethacin (1-10 mg/kg), stress (1 and 3 mg/kg) and reserpine (0.3-10 mg/kg)-induced erosions. The compound lacked antisecretory activity in the pylorus-ligated rats (10 mg/kg p.o.) but increased total gastric mucus (N-acetylneuraminic acid measurements) (1-10 mg/kg p.o.). SCH 12223 (10 and 30 mg/kg p.o.) attenuated intestinal lesions provoked by indomethacin (20 mg/kg p.o. or s.c.) and the protected animals showed better weight gain and food intake than controls. In a 38-day study, SCH 12223 also improved survival from indomethacin lethality (6 of 16 vs. 16 of 16 in the control, P less than .05). The protection cannot be attributed to changes in biliary excretion and plasma levels of indomethacin. We conclude that SCH 12223 is a unique agent which protects both gastric and intestinal epithelia from noxious stimuli, a feature shared by prostaglandins.
authors.affiliation: Department of Pharmacology, Schering-Plough Corporation, Bloomfield, New Jersey.
authors.forename: P J
authors.initials: PJ
authors.lastname: Chiu
authors.forename: A
authors.initials: A
authors.lastname: Barnett
authors.forename: M
authors.initials: M
authors.lastname: Siegel
authors.forename: A D
authors.initials: AD
authors.lastname: Brown
authors.forename: C
authors.initials: C
authors.lastname: Gerhart
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000897:Anti-Ulcer Agents; D001241:Aspirin / Q000037:antagonists & inhibitors; D000431:Ethanol / Q000037:antagonists & inhibitors; D005753:Gastric Mucosa / Q000187:drug effects; D007213:Indomethacin / Q000037:antagonists & inhibitors; D007275:Injections, Intravenous; D007410:Intestinal Diseases / Q000139:chemically induced / Q000517:prevention & control*; D008297:Male; D009287:Naphthyridines / Q000494:pharmacology*; D051381:Rats; D012110:Reserpine / Q000037:antagonists & inhibitors; D013276:Stomach Ulcer / Q000139:chemically induced / Q000517:prevention & control*
chemical_list: D000897:Anti-Ulcer Agents; D009287:Naphthyridines; D000431:Ethanol; C056845:SCH 12223; D012110:Reserpine; D001241:Aspirin; D007213:Indomethacin