Pharmacological properties of a newly synthesized H(+)/K(+) ATPase inhibitor, 1-(2-methyl-4-methoxyphenyl)-4-.
A new compound, 1-(2-methyl-4-methoxyphenyl)-4-[(3-hydroxypropyl)amino]-6-methyl-2,3-dihydropyrrolo[3,2-c]quinoline (DBM-819), given intraduodenally in pylorus-ligated rats, inhibited basal acid secretion with an ED(50) value of 3.5 mg/kg. In addition, DBM-819 reduced histamine- and pentagastrin-stimulated gastric acid secretion with ED(50) values of 4.0 and 5.1 mg/kg, respectively. The duration of the anti-secretory effect was approximately 18 h when DBM-819 was administered orally to rats with a chronic gastric fistula. Oral administration of DBM-819 protected against gastric lesions induced by ethanol, NaOH, indomethacin and aspirin, and the duodenal ulcer induced by cysteamine, in a dose-dependent manner with ED(50) values of 7.0, 20, 3.1, 4.0 and 6.0 mg/kg, respectively. Taken together, these results suggest that DBM-819 acts as an effective oral anti-ulcer agent in vivo, and that DBM-819 could be developed as a new therapeutic agent for peptic ulcer disease.
Cheon
H G
HG
Pharmaceutical Screening Center, Korea Research Institute of Chemical Technology, 100 Jang-Dong, Yusong-Gu, 305-343, Taejon, South Korea
Lee
S S
SS
Lim
H
H
Lee
D H
DH
D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology; D001241:Aspirin / Q000008:administration & dosage; D003543:Cysteamine / Q000008:administration & dosage; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D000431:Ethanol / Q000008:administration & dosage; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000378:metabolism; D017506:H(+)-K(+)-Exchanging ATPase / Q000378:metabolism; D007213:Indomethacin / Q000008:administration & dosage; D009853:Omeprazole / Q000494:pharmacology; D010477:Perfusion; D054328:Proton Pump Inhibitors; D011758:Pyrroles / Q000494:pharmacology*; D011804:Quinolines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012972:Sodium Hydroxide / Q000008:administration & dosage; D013270:Stomach / Q000187:drug effects / Q000473:pathology; D013276:Stomach Ulcer / Q000139:chemically induced / Q000517:prevention & control; D013997:Time Factors
D000897:Anti-Ulcer Agents; C419624:DBM-819; D004791:Enzyme Inhibitors; D054328:Proton Pump Inhibitors; D011758:Pyrroles; D011804:Quinolines; D000431:Ethanol; D012972:Sodium Hydroxide; D003543:Cysteamine; D017506:H(+)-K(+)-Exchanging ATPase; D009853:Omeprazole; D001241:Aspirin; D007213:Indomethacin