Effects of Y-20811, a long-lasting thromboxane synthetase inhibitor, on thromboxane production and platelet function.
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.
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D006168:Guinea Pigs; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D008861:Microsomes / Q000201:enzymology; D010974:Platelet Aggregation / Q000187:drug effects*; D010976:Platelet Count; D011655:Pulmonary Embolism / Q000097:blood / Q000139:chemically induced; D011817:Rabbits; D012669:Seminal Vesicles / Q000201:enzymology; D012756:Sheep; D013045:Species Specificity; D013929:Thromboxane B2 / Q000097:blood; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors* / Q000097:blood; D013931:Thromboxanes / Q000097:blood*
D001095:Arachidonic Acids; D007093:Imidazoles; D013931:Thromboxanes; C049966:Y 20811; D016718:Arachidonic Acid; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D013930:Thromboxane-A Synthase