Effects of Y-20811, a long-lasting thromboxane synthetase inhibitor, on thromboxane production and platelet function

Thromb Res. 1986 Aug 15;43(4):455-68. doi: 10.1016/0049-3848(86)90090-3.

Abstract

Effects of a new imidazole derivative, sodium 4-[alpha-hydroxy-5-(imidazolyl)-2-methylbenzyl]-3,5-dimethyl benzoate dihydrate (Y-20811), on thromboxane (TX) production and platelet aggregation were investigated. Y-20811 inhibited TX synthetase (IC50 = 2.2 X 10(-8) M) and platelet aggregation induced by arachidonic acid (AA) in human, guinea pig and rabbit platelets in vitro. Administered orally to rabbits, Y-20811 at a dose of 1 mg/kg decreased serum TXB2 concomitant with increasing 6-keto PGF1 alpha and at a dose of 3 mg/kg inhibited AA-induced platelet aggregation, in both cases for at least 48 hours. Y-20811 (0.3 mg/kg/day) administered to rabbits for 7 days decreased serum TXB2 levels by 50-90% during the medication, and these levels were restored to initial values 3 days after withdrawal of the drug. At a dose of 1 mg/kg Y-20811 protected rabbits against death induced by AA (2 mg/kg). These results indicate that Y-20811 is a selective and long-lasting TX synthetase inhibitor and an anti-aggregating agent useful in preventing thrombotic disorders.

MeSH terms

  • 6-Ketoprostaglandin F1 alpha / blood
  • Animals
  • Arachidonic Acid
  • Arachidonic Acids / pharmacology
  • Blood Platelets / drug effects
  • Blood Platelets / enzymology
  • Blood Platelets / physiology*
  • Guinea Pigs
  • Humans
  • Imidazoles / pharmacology*
  • In Vitro Techniques
  • Kinetics
  • Male
  • Microsomes / enzymology
  • Platelet Aggregation / drug effects*
  • Platelet Count
  • Pulmonary Embolism / blood
  • Pulmonary Embolism / chemically induced
  • Rabbits
  • Seminal Vesicles / enzymology
  • Sheep
  • Species Specificity
  • Thromboxane B2 / blood
  • Thromboxane-A Synthase / antagonists & inhibitors*
  • Thromboxane-A Synthase / blood
  • Thromboxanes / blood*

Substances

  • Arachidonic Acids
  • Imidazoles
  • Thromboxanes
  • Y 20811
  • Arachidonic Acid
  • Thromboxane B2
  • 6-Ketoprostaglandin F1 alpha
  • Thromboxane-A Synthase