Pharmacological properties of a newly synthesized H(+)/K(+) ATPase inhibitor, 1-(2-methyl-4-methoxyphenyl)-4-

Eur J Pharmacol. 2001 Jan 5;411(1-2):187-192. doi: 10.1016/s0014-2999(00)00920-1.

Abstract

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.

MeSH terms

  • Animals
  • Anti-Ulcer Agents / pharmacology
  • Aspirin / administration & dosage
  • Cysteamine / administration & dosage
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / pharmacology*
  • Ethanol / administration & dosage
  • Gastric Acid / metabolism
  • Gastric Mucosa / metabolism
  • H(+)-K(+)-Exchanging ATPase / metabolism
  • Indomethacin / administration & dosage
  • Omeprazole / pharmacology
  • Perfusion
  • Proton Pump Inhibitors*
  • Pyrroles / pharmacology*
  • Quinolines / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Sodium Hydroxide / administration & dosage
  • Stomach / drug effects
  • Stomach / pathology
  • Stomach Ulcer / chemically induced
  • Stomach Ulcer / prevention & control
  • Time Factors

Substances

  • Anti-Ulcer Agents
  • DBM-819
  • Enzyme Inhibitors
  • Proton Pump Inhibitors
  • Pyrroles
  • Quinolines
  • Ethanol
  • Sodium Hydroxide
  • Cysteamine
  • H(+)-K(+)-Exchanging ATPase
  • Omeprazole
  • Aspirin
  • Indomethacin