Paroxetine decreases platelet serotonin storage and platelet function in human beings
| Autor: | Bernd Jilma, Martin Aigner, Jesusa Entlicher, Christa Drucker, Hans-Georg Eichler, Nicole Hergovich |
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| Rok vydání: | 2000 |
| Předmět: |
Adult
Blood Platelets Male Agonist Serotonin medicine.medical_specialty medicine.drug_class Thrombin Double-Blind Method Internal medicine von Willebrand Factor Thrombin receptor medicine Humans Pharmacology (medical) Platelet Platelet activation Pharmacology Cross-Over Studies business.industry Paroxetine P-Selectin Endocrinology Coagulation Antidepressant Prothrombin business Selective Serotonin Reuptake Inhibitors medicine.drug |
| Zdroj: | Clinical Pharmacology & Therapeutics. 68:435-442 |
| ISSN: | 0009-9236 |
| DOI: | 10.1067/mcp.2000.110456 |
| Popis: | Background Serotonin is a platelet agonist and potent vasoconstrictor that has recently received attention concerning its potential role in acute coronary artery thrombosis. Selective serotonin-reuptake inhibitors, such as paroxetine, are widely used antidepressant agents. We sought to characterize the potential inhibitory effect of paroxetine on platelet function. Methods Healthy male volunteers received 20 mg/d paroxetine for 2 weeks in a randomized, double-blind, placebo-controlled, two-way cross-over trial Results Paroxetine decreased intraplatelet serotonin concentrations by −83% (P < .01). This inhibited platelet plug formation as reflected by a 31% prolongation of closure time measured with the platelet function analyzer-100 (P < .05). Furthermore, paroxetine lowered expression of the platelet activation marker CD63 in response to two different concentrations of thrombin receptor–activating peptide (P < .01). Plasma concentrations of prothrombin fragment, von Willebrand factor antigen, and circulating P-selectin remained unchanged in either period, indicating that paroxetine does not increase activation of coagulation, endothelium, or platelets in vivo, underlining a favorable safety profile. Conclusions Paroxetine substantially decreases intraplatelet serotonin content and thereby reduces platelet plug formation under shear stress, and responsiveness to thrombin receptor activating peptide–induced platelet activation. Further studies will reveal whether these pharmacodynamic effects can be exploited for treatment of thrombotic artery disease. (Clin Pharmacol Ther 2000;68:435-42.) Clinical Pharmacology & Therapeutics (2000) 68, 435–442; doi: 10.1067/mcp.2000.110456 |
| Databáze: | OpenAIRE |
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