Drugs online research references
aol.com
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, increased platelet 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, by expression 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 microM ADP (P =, 0.002), by 10 microM ADP (P = 0.0017), by collagen (P = 0.008), and by thrombin (P = 0.026). Whole blood platelet aggregability was also significantly reduced when induced by 20 microM ADP (P = 0.006), and by collagen (P = 0.01). Surface expression of CD9 (P = 0.004), GP Ib (P = 0.0001), GP IIb/IIIa (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 significant inhibition of GP IIb/IIIa (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 the mortality benefits of SSRIs after ischemic events including myocardial infarction and stroke. Copyright 2001 Academic Press.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11394937&dopt=Abstract
word match zoloft online literature
psychiatry.umsmed.edu
Corticotropin-releasing factor (CRF) and thyrotropin-releasing hormone (TRH) are two neuropeptides that exhibit increased cerebrospinal fluid (CSF) concentrations during major depressive episodes while somatostatin (somatotropin-release inhibiting factor, SRIF) is decreased. Clinical and basic research findings indicate that clinically effective antidepressant therapies often normalize the indicators of CRF and TRH hypersecretion as well as SRIF hyposecretion. The olfactory bulbectomized (OBX) rat is used to screen potential antidepressant drugs for clinical efficacy. This model requires chronic administration of the antidepressant drug to normalize OBX-induced behaviors such as increased locomotion in a novel environment. This report describes the regional brain concentration changes in CRF, TRH and SRIF produced by OBX and demonstrates the ability of the selective serotonin re-uptake inhibitor and antidepressant drug, sertraline (10 mg/kg), to normalize certain of these alterations in regional neuropeptide concentrations as well as normalizing OBX-induced increases in locomotor activity. OBX-induced increases in CRF concentrations in the hypothalamus and bed nucleus of the stria terminalis were specifically and significantly decreased by sertraline. OBX-induced increases in TRH concentrations in the hypothalamus were reversed by sertraline. The concentration of SRIF was significantly reduced by OBX in the anterior caudate and the piriform cortex, but sertraline reversed these changes only in the anterior caudate.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11420095&dopt=Abstract
word match zoloft online literature
Clin Pharmacol Ther. 2001 Jul;70(1):42-7.
Pharmacokinetics of sertraline in relation to genetic polymorphism of CYP2C19.
Wang JH, Liu ZQ, Wang W, Chen XP, Shu Y, He N, Zhou HH.
Pharmacogenetics Research Institute, Hunan Medical University, China.
OBJECTIVE: Our objective was to evaluate the relationship between the disposition of sertraline and the presence of the CYP2C19 gene and to define the contribution of cytochrome P450 2C19 (CYP2C19) to sertraline N-demethylation. METHODS: A single oral 100-mg dose of sertraline was administered to 6 subjects who were extensive metabolizers and 6 subjects who were poor metabolizers recruited from 77 healthy Chinese volunteers whose genotypes were predetermined by polymerase chain reaction-based amplification, followed by restriction fragment length polymorphism analysis. Phenotypes were determined by use of the omeprazole metabolic rate. The plasma concentrations of sertraline and desmethylsertraline were determined by gas chromatography with electron-capture detection. RESULTS: Six poor metabolizers with m1 mutation had area under the plasma concentration versus time curve (AUC(0-infinity)) values (983.6 +/- 199.3 microg x h/L versus 697.6 +/- 133.0 microg x h/L; P <.05) and terminal elimination half-life values of sertraline (35.5 +/- 5.6 hours versus 23.5 +/- 4.4 hours; P <.01) that were significantly higher than the values in 6 extensive metabolizers who were either homozygous or heterozygous for CYP2C19*1. The oral clearance of sertraline in poor metabolizers (105.3 +/- 19.4 L/h) was significantly lower than that of extensive metabolizers (148.4 +/- 28.6 L/h). The area under the concentration-time curve from 0 to 144 hours and the maximum plasma concentration of desmethylsertraline in poor metabolizers were significantly lower than the values of extensive metabolizers (627.6 +/- 203.8 microg x h/L versus 972.1 +/- 270.3 microg x h/L; P <.05; and 23.6 +/- 6.5 nmol/L versus 32.4 +/- 8.2 nmol/L; P <.01; respectively). CONCLUSIONS: The polymorphic CYP2C19 appears to be a major enzyme involved in the N-demethylation of sertraline, and both extensive and poor metabolizers had marked differences in the disposition of sertraline.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11452243&dopt=Abstract
word match zoloft online literature
Herbs and Pharmaceuticals Online ||
Hair Million herbal formula for hair loss and hair growth ||
Antibiotics and prescription medications online literature ||