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Effect of 1,6-dihydro-2-[2-(2-methylpropoxy)anilino]-6-oxo-5-pyrimidinecarboxylic acid on gastric mucosal defensive factors and gastric secretion in rats.

Abstract
1,6-dihydro-2-[2-(2-methylpropoxy)anilino]-6-oxo-5-pyrimidinecarbo xylic acid, (MAR-99, CAS 98772-05-5) (10-30 mg/kg i.g.) improved the reduction of gastric blood flow rate induced by the administration of 99.5% ethanol or acidified-acetylsalicylic acid (ASA). In addition, MAR-99 (3 x 10(-6)-3 x 10(-5) mol/l) protected dose-dependently the damage of epithelial cells induced by ulcerogenic agents such as ethanol or acidified-ASA. MAR-99 (1-10 mg/kg p.o.) prevented dose-dependently the reduction of hexosamine content in glandular stomach. Furthermore, MAR-99 (10-30 mg/kg i.g.) improved the decrease in gastric potential difference induced by 99.5% ethanol and acidified-ASA. MAR-99 (10-30 mg/kg p.o.) significantly inhibited the lesion formation induced by 99.5% ethanol and such effect of this compound was not attenuated by the pretreatment with indomethacin. Furthermore MAR-99 (10 and 30 mg/kg p.o.) had no effect on the prostaglandins (PGE2 and I2) contents in the stomach of normal rats. In pylorus-ligated rats, MAR-99 (3-100 mg/kg i.d.) showed a weak or no effect on acidity and pepsin activity in gastric juice, although this compound decreased dose-dependently the volume of gastric juice. In perfused stomachs, MAR-99 (30-100 mg/kg i.d.) slightly prevented the acid secretion induced by carbachol and pentagastrin. However, MAR-99 did not affect the acid secretion stimulated by histamine. These results indicated that anti-ulcer effect of MAR-99 was mainly due to maintenance of the gastric mucosal resistance.
AuthorsY Ishizuka, T Kamisaki, N Okamoto, M Matsuda, I Shimazaki, I Kimura, A Kamiya, M Kataoka, M Kawashima, K Terashima
JournalArzneimittel-Forschung (Arzneimittelforschung) Vol. 44 Issue 5 Pg. 620-6 (May 1994) ISSN: 0004-4172 [Print] Germany
PMID8024635 (Publication Type: Journal Article)
Chemical References
  • Anti-Ulcer Agents
  • Hexosamines
  • Pyrimidines
  • Ethanol
  • Histamine
  • Carbachol
  • MAR 99
  • Pentagastrin
  • Aspirin
  • Indomethacin
Topics
  • Animals
  • Anti-Ulcer Agents (pharmacology)
  • Aspirin (pharmacology)
  • Carbachol (pharmacology)
  • Epithelial Cells
  • Epithelium (drug effects)
  • Ethanol (pharmacology)
  • Gastric Acid (metabolism)
  • Gastric Mucosa (drug effects, metabolism, physiology)
  • Hexosamines (metabolism)
  • Histamine (pharmacology)
  • In Vitro Techniques
  • Indomethacin (pharmacology)
  • Male
  • Membrane Potentials (drug effects)
  • Mucus (metabolism)
  • Pentagastrin (pharmacology)
  • Pyrimidines (pharmacology)
  • Rats
  • Rats, Sprague-Dawley
  • Regional Blood Flow (drug effects)
  • Stomach (blood supply)

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