Antiplatelet Properties of Escitalopram in Patients with the Metabolic Syndrome: A Dose-Ranging In Vitro Study
| Autor: | Dan Atar, Victor L. Serebruany, François Lespérance, Alex I. Malinin, Nancy Frasure-Smith, Louis T. van Zyl, Alex N. Pokov |
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| Rok vydání: | 2007 |
| Předmět: |
Adult
Male medicine.medical_specialty Platelet Function Tests Citalopram In Vitro Techniques Pharmacology Therapeutic index Metabolic Diseases Internal medicine medicine Humans Platelet Prospective Studies Platelet activation Receptor Aged Aged 80 and over Analysis of Variance Dose-Response Relationship Drug CD63 business.industry Middle Aged Flow Cytometry Platelet Activation Psychiatry and Mental health Endocrinology Female Serotonin business Reuptake inhibitor Biomarkers Platelet Aggregation Inhibitors Ex vivo |
| Zdroj: | Neuropsychopharmacology. 32:2369-2374 |
| ISSN: | 1740-634X 0893-133X |
| Popis: | There is an increasing body of evidence suggesting that selective serotonin reuptake inhibitors exhibit clinical benefit beyond treating depression, by simultaneously inhibiting platelet activity. We recently demonstrated that escitalopram (ESC), but not its major metabolites, inhibits multiple platelet biomarkers in healthy volunteers. Considering that the metabolic syndrome represents one of the major risk factors for vascular disease, we here determined how ESC affects platelet activity in such patients. We assessed the in vitro effects of preincubation with escalating (50-200 nM/l) concentrations of ESC on platelet aggregation, expression of major surface receptors by flow cytometry, and quantitatively by platelet function analyzers. Blood samples were obtained from 20 aspirin-naïve patients with documented metabolic syndrome. Pretreatment of blood samples with medium (150 nM/l), or high (200 nM/l) doses of ESC resulted in a significant inhibition of platelet aggregation induced by ADP (p=0.007) and by collagen (p=0.004). Surface platelet expression of GPIb (CD42, p=0.03), LAMP-3 (CD63, p=0.04), and GP37 (CD165, p=0.03) was decreased in the ESC-pretreated samples. Closure time by the PFA-100 analyzer was prolonged after the 200 nM/l dose (p=0.02), indicating platelet inhibition under high shear conditions. On the other hand, the lowest tested concentration of ESC (50 nM/l) did not affect platelet activity in these patients. The in vitro antiplatelet characteristics of ESC in patients with the metabolic syndrome are similar to those in healthy volunteers. However, higher ESC doses are required to induce equally potent platelet inhibition. These data justify prospective ex vivo studies with the highest therapeutic dose to determine the potential clinical advantage of ESC in high-risk patients with vascular disease. |
| Databáze: | OpenAIRE |
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