Thromboxane A₂ Antagonistic Action of a New Anti-Ulcer Agent, Azuletil Sodium (KT1-32)

Abstract

The TXA₂/PGH₂ receptor antagonistic activity of azuletil sodium (KT1-32), a new anti-ulcer agent, was examined. KT1-32 competitively antagonized the contraction of canine gastric arteries induced by U-46619, PGF_2a and PGE₂, whereas it had no effect on the PGF_2a-, PGE₂-and LTD₄-induced contraction of guinea-pig ileum, which was not affected by U-46619. In anesthetized dogs, KT1-32 significantly reduced the U-46619-induced decrease in gastric arterial blood flow. Gastric contraction induced by U-46619 in anesthetized rats was markedly inhibited by KT1-32. KT1-32 showed no influence on TXA₂ synthetase and cyclooxygenase activities. These results indicate that KT1-32 is a competitive TXA₂/PGH₂ receptor antagonist, which may be important as to the effectiveness of KT1-32 against gastric ulcer.

Key Words:

• Azuletil sodium
• gastric arterial blood flow
• gastric contraction
• KT1-32
• thromboxane A₂