Effects of camonagrel, a selective inhibitor of platelet thromboxane synthase, on the platelet-subendothelium interaction.
The aim of this study was to compare the effects of a new thromboxane synthase inhibitor, camonagrel, on platelet aggregation and platelet-subendothelium interaction under flow conditions, in comparison with a standard thromboxane synthase inhibitor (dazoxiben) and a cyclooxygenase inhibitor (acetylsalicylic acid). With respect to platelet aggregation in whole blood, the 50% inhibitory concentrations (IC(50)) of camonagrel were between 318 and 797 micromol/l after induction with collagen and adenosine 5'-diphosphate, respectively. For inhibition of thromboxane B(2) synthesis, the IC(50) values were 868 +/- 68 micromol/l; prostaglandin E(2) was inhibited only by acetylsalicylic acid (IC(50) for camonagrel >2,000 micromol/l), and the leukocyte 6-keto-PGF(1alpha) level was increased by camonagrel. The greatest reduction in percentage subendothelial surface occupied by platelets (mainly in the thrombi) after blood perfusion was seen after incubation with camonagrel in the range of concentrations that inhibited collagen-induced platelet aggregation. In conclusion, camonagrel reduced platelet-subendothelium interaction under flow conditions, showing this effect in a range of concentrations lower than in inhibition of platelet aggregation.
Villalobos
M A
MA
Department of Human Anatomy, University of Málaga, School of Medicine, Málaga, Spain.
De La Cruz
J P
JP
Escalante
R
R
Arrebola
M M
MM
Guerrero
A
A
Sánchez de la Cuesta
F
F
D000293:Adolescent; D000328:Adult; D000818:Animals; D001241:Aspirin / Q000037:antagonists & inhibitors / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D007189:Indans / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects; D011453:Prostaglandins / Q000096:biosynthesis; D011458:Prostaglandins E / Q000096:biosynthesis; D011817:Rabbits; D013927:Thrombosis / Q000209:etiology; D013929:Thromboxane B2 / Q000096:biosynthesis*; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors / Q000097:blood* / Q000187:drug effects; D017539:Tunica Intima / Q000187:drug effects* / Q000502:physiology
D007093:Imidazoles; D007189:Indans; D011453:Prostaglandins; D011458:Prostaglandins E; C029166:dazoxiben; D013929:Thromboxane B2; D013930:Thromboxane-A Synthase; D001241:Aspirin; C103583:camonagrel