Thromboxane A2 antagonistic action of a new anti-ulcer agent, azuletil sodium (KT1-32).
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.
Mochizuki
S
S
Research Laboratory, Kotobuki Seiyaku Co., Ltd., Nagano, Japan.
Wakabayashi
S
S
Tomiyama
A
A
Satake
N
N
Shibata
S
S
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D001158:Arteries; D052176:Azulenes; D004285:Dogs; D006168:Guinea Pigs; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D011450:Prostaglandin Endoperoxides, Synthetic / Q000037:antagonists & inhibitors / Q000494:pharmacology; D011708:Pylorus / Q000098:blood supply; D051381:Rats; D011919:Rats, Inbred Strains; D012039:Regional Blood Flow / Q000187:drug effects; D012717:Sesquiterpenes / Q000494:pharmacology*; D013270:Stomach / Q000098:blood supply / Q000187:drug effects; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors*; D014661:Vasoconstriction / Q000187:drug effects
D000897:Anti-Ulcer Agents; D052176:Azulenes; D011450:Prostaglandin Endoperoxides, Synthetic; D012717:Sesquiterpenes; C035058:azulene SN; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; C061956:azuletil