Effects of 12-sulfodehydroabietic acid monosodium salt (TA-2711), a new anti-ulcer agent, on gastric secretion and experimental ulcers in rats.
Effects of 12-sulfodehydroabietic acid monosodium salt (TA-2711), a new anti-ulcer agent, on gastric secretion and experimental ulcers were investigated in rats. Oral administration of TA-2711 at doses of 25 to 100 mg/kg immediately after pyloric ligation markedly reduced pepsin activity and slightly lowered acid concentration without affecting the volume of gastric juice. Addition of TA-2711 (0.25-16 mg/ml) directly to gastric juice also reduced pepsin activity in vitro. Oral TA-2711 dose-relatedly inhibited the formation of pylorus-ligated ulcers (50-200 mg/kg), aspirin-induced gastric erosions (25-100 mg/kg) and cysteamine-induced duodenal ulcers (100-800 mg/kg). In addition, this drug prevented both the formation of gastric lesions (6.3-100 mg/kg, p.o.) and the fall in gastric potential difference (100 mg/kg, p.o.) induced by ethanol. The preventive effect against ethanol-induced lesions was suppressed by pretreatment with indomethacin (10 mg/kg, s.c.). Intravenous dosing of TA-2711 (10-100 mg/kg) never produced such effects on ethanol-induced lesions and pepsin activity as observed by oral administration. These results indicate that TA-2711 exerts its anti-ulcer effect by a local action, and it is suggested that both reduction of pepsin activity and a mucosal prostaglandin-mediated process are involved in the anti-ulcer action of TA-2711.
Onoda
Y
Y
Biological Research Laboratory, Tanabe Seiyaku Co., Ltd., Saitama, Japan.
Magaribuchi
T
T
Tamaki
H
H
D045784:Abietanes; D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002229:Carbenoxolone / Q000627:therapeutic use; D002927:Cimetidine / Q000627:therapeutic use; D004224:Diterpenes / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D005750:Gastric Juice / Q000187:drug effects / Q000201:enzymology; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D010434:Pepsin A / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013276:Stomach Ulcer / Q000139:chemically induced / Q000188:drug therapy* / Q000517:prevention & control; D013315:Stress, Psychological / Q000150:complications; D013392:Sucralfate / Q000627:therapeutic use
D045784:Abietanes; D000897:Anti-Ulcer Agents; D004224:Diterpenes; C061681:ecabet; D013392:Sucralfate; D002927:Cimetidine; D010434:Pepsin A; D002229:Carbenoxolone