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Titolo:
Platelet inhibition by sertraline and N-desmethylsertraline: A possible missing link between depression, coronary events, and mortality benefits of selective serotonin reuptake inhibitors
Autore:
Serebruany, VL; Gurbel, PA; O Connor, CM;
Indirizzi:
Johns Hopkins Univ, Sinai Ctr Thrombosis Res, Baltimore, MD USA Johns Hopkins Univ Baltimore MD USA tr Thrombosis Res, Baltimore, MD USA Duke Univ, Med Ctr, Durham, NC USA Duke Univ Durham NC USADuke Univ, Med Ctr, Durham, NC USA
Titolo Testata:
PHARMACOLOGICAL RESEARCH
fascicolo: 5, volume: 43, anno: 2001,
pagine: 453 - 461
SICI:
1043-6618(200105)43:5<453:PIBSAN>2.0.ZU;2-Y
Fonte:
ISI
Lingua:
ENG
Soggetto:
ACUTE MYOCARDIAL-INFARCTION; MAJOR RECEPTOR EXPRESSION; PLASMA FACTOR(S); BLOOD-PLATELETS; ARTERY DISEASE; WHOLE-BLOOD; G-PROTEINS; AGGREGATION; FLUOXETINE; BINDING;
Keywords:
selective serotonin reuptake inhibitors; depression; platelets;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
63
Recensione:
Indirizzi per estratti:
Indirizzo: Serebruany, VL Sinai Hosp, Thrombosis Res Ctr, 2401 W Belvedere Ave,Schaprio Res Bldg,R 202, Baltimore, MD 21215 USA Sinai Hosp 2401 W Belvedere Ave,Schaprio Res Bldg,R 202 Baltimore MD USA 21215
Citazione:
V.L. Serebruany et al., "Platelet inhibition by sertraline and N-desmethylsertraline: A possible missing link between depression, coronary events, and mortality benefits of selective serotonin reuptake inhibitors", PHARMAC RES, 43(5), 2001, pp. 453-461

Abstract

Recently, clinical depression has been identified as an independent risk factor for increased mortality in patients following acute coronary events. Although the underlying mechanisms of this link remain uncertain, increasedplatelet activity has been suggested but never proven as the mechanism responsible for this association. Sertraline hydrochloride is a selective serotonin reuptake inhibitor (SSRI), and is an effective antidepressant agent. Its major liver metabolite, N-desmethylsertraline (NDMS), is known to be neurologically inactive. We assessed the in vitro effects of escalating concentrations of sertraline and NDMS on human platelets by aggregometry in plasma and whole blood, byexpression of major surface receptors with flow cytometry in washed cells and in the whole blood, and quantitatively by various platelet function analysers in healthy volunteers and patients with coronary artery disease. Pretreatment of blood samples with sertraline and NDMS resulted in a dose-dependent inhibition of platelet-rich plasma aggregation induced by 5 muM ADP (P = 0.002), by 10 muM ADP (P = 0.0017), by collagen (P = 0.008), and by thrombin(P = 0.026). Whole blood platelet aggregability was also significantlyreduced when induced by 20 muM ADP(P = 0.006), and by collagen (P = 0.01). Surface expression of CD9 (P = 0.004), GP Ib (P = 0.0001), GP IIb/llla (P = 0.007), VLA-2 (P = 0.01), P-selectin (P = 0.02), and PECAM-1 (P = 0.01), but not the vitronectin receptor, was also reduced in sertraline and NDMS pretreated washed platelets. Whole blood flow cytometry revealed significantinhibition of GP IIb/IIla(P = 0.008), and P-selectin expression (P = 0.0001) in NDMS treated samples. Closure time was delayed for the collagen-ADP cartridge (P = 0.009), and for the collagen-epinephrin cartridge (P = 0.01),indicating platelet inhibition in whole blood under high shear conditions. Rapid platelet-function assay revealed a decreased (P = 0.002) ability of platelets to agglutinate fibrinogen-coated beads, suggesting GP IIb/IIIa inhibition. Both sertraline, and its neurologically inactive metabolite NDMS, exhibited significant dose-dependent inhibition of human platelets. The documented anti-platelet effects of sertraline and NDMS may be directly related to themortality benefits of SSRIs after ischemic events including myocardial infarction and stroke. (C) 2001 Academic Press.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 25/01/20 alle ore 19:06:50