15-hydroxy-11-alpha-9-alpha-(epoxymethano)prosta-5-13-dienoic-acid and azuletil

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, PGF2 alpha, and PGE2, whereas it had no effect on the PGF2 alpha-, 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.

Topics: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Animals; Anti-Ulcer Agents; Arteries; Azulenes; Dogs; Guinea Pigs; Male; Muscle Contraction; Prostaglandin Endoperoxides, Synthetic; Pylorus; Rats; Rats, Inbred Strains; Regional Blood Flow; Sesquiterpenes; Stomach; Thromboxane A2; Vasoconstriction