Inhibition of platelet aggregation in vitro and ex vivo by the new thromboxane antagonist (3R)-3-(4-fluorophenylsulfonamido)-1,2,3,4-tetrahydro-9- carbazolepropanoic acid.
(3R)-3-(4-Fluorophenylsulfonamido)-1,2,3,4-tetrahydro-9-carbazo lepropanoic acid (Bay u 3405) was tested for inhibition of platelet aggregation in vitro (human platelet rich plasma) and ex vivo (rat). Aggregation induced by collagen, arachidonic acid, thrombin, adenosine diphosphate (ADP, biphasic response), epinephrine and U 46619 was inhibited at minimum effective concentrations of 0.01 to 0.1 micrograms/ml in vitro. Following oral administration to rats the ED50 for the dose-dependent inhibition was 36 micrograms/kg. At a dose of 100 micrograms/kg p.o. significant inhibition was obtained up to 16 h. Bay u 3405 is considered a potential drug for treatment of some cardiovascular disorders.
Seuter
F
F
Institut für Pharmakologie, Bayer AG, Wuppertal, Fed. Rep. of Germany.
Perzborn
E
E
Rosentreter
U
U
Böshagen
H
H
Fiedler
V B
VB
D000818:Animals; D002227:Carbazoles / Q000494:pharmacology*; D003094:Collagen / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors; D051381:Rats; D011919:Rats, Inbred Strains; D013449:Sulfonamides / Q000494:pharmacology*; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors*
D002227:Carbazoles; D010975:Platelet Aggregation Inhibitors; D013449:Sulfonamides; D013928:Thromboxane A2; D003094:Collagen; C063119:ramatroban