Effect of ritanserin, a 5-hydroxytryptamine2-receptor antagonist, on platelet function and thrombin generation at the site of plug formation in vivo.
To investigate the role of serotonin in platelet plug formation we studied, in eight healthy volunteers, the effect of ritanserin (a 5-hydroxytryptamine2-receptor antagonist) on the platelet release reaction (represented by beta-thromboglobulin release) platelet prostaglandin metabolism (represented by thromboxane B2 formation), and thrombin generation (represented by fibrinopeptide A formation) in the microvasculature. After administration of ritanserin lower amounts of thromboxane B1 were generated in the initial stages of plug formation, suggesting an inhibitory effect on the platelet prostaglandin metabolism. Similar amounts of beta-thromboglobulin were released after the administration of ritanserin compared with placebo, indicating a minor effect of ritanserin on the release reaction. Reduction of thrombin formation by ritanserin in the later stages of hemostasis suggested an inhibitory effect of this substance on the procoagulatory activity of platelets or endothelial cells. This could be attributable to interference with the formation or function of coagulation factor complexes on cell surfaces, or it could be the consequence of a reduction of the platelet activity.
Wagner
B
B
Department of Medicine I, University of Vienna, Austria.
Schneider
B
B
Blöchl-Daum
B
B
Speiser
W
W
Brenner
B
B
Eichler
H G
HG
Lechner
K
K
Kyrle
P A
PA
D000328:Adult; D001760:Bleeding Time; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology*; D004311:Double-Blind Method; D005344:Fibrinopeptide A / Q000096:biosynthesis / Q000737:chemistry; D006801:Humans; D010880:Piperidines / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D016713:Ritanserin; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013917:Thrombin / Q000096:biosynthesis* / Q000187:drug effects; D013929:Thromboxane B2 / Q000096:biosynthesis / Q000097:blood; D001620:beta-Thromboglobulin / Q000737:chemistry / Q000502:physiology
D010880:Piperidines; D010975:Platelet Aggregation Inhibitors; D012702:Serotonin Antagonists; D001620:beta-Thromboglobulin; D016713:Ritanserin; D005344:Fibrinopeptide A; D013929:Thromboxane B2; D013917:Thrombin