Drugs online research references
J Am Acad Child Adolesc Psychiatry. 1998 Jul;37(7):777-84.
Platelet serotonin transporter in depressed children and adolescents: 3H-paroxetine platelet binding before and after sertraline.
Sallee FR, Hilal R, Dougherty D, Beach K, Nesbitt L.
Medical University of South Carolina, Charleston, USA.
OBJECTIVE: To evaluate serotonin transporter protein (5HTPR) binding in platelets from children and adolescents with major depression (MDD) compared to normal controls using the selective ligand 3H-paroxetine. METHOD: Children and adolescents with MDD (n = 24) defined by DSM-III-R criteria and normal controls (n = 22) were compared by platelet 5HTPR kinetic analysis with the hypothesis that 5HTPR is reduced in MDD. A subset of MDD subjects (n = 18) continued to participate in a fixed-dose, open-label sertraline trial for 6 weeks followed by drug-free washout and repeated 5HTPR analysis. RESULTS: Sex, prepubertal status, and age had no effect on 5HTPR. Medication-free MDD subjects differed from controls in reduced binding capacity (Bmax) (p < .001). Sertraline therapy decreased binding affinity from baseline non-selectively (p < .05), and Bmax elevation from baseline was associated with nonresponse and suicide attempt history. CONCLUSION: Earlier literature in this population is replicated with regard to reduced platelet 5HTPR Bmax in MDD. Findings support a continuum of 5HTPR involvement in MDD across the developmental spectrum.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9666634&dopt=Abstract
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Mol Psychiatry. 1998 May;3(3):270-3.
Evidence for linkage disequilibrium between serotonin transporter protein gene (SLC6A4) and obsessive compulsive disorder.
McDougle CJ, Epperson CN, Price LH, Gelernter J.
Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
Obsessive compulsive disorder (OCD) is characterized by recurrent and intrusive thoughts that are distressing (obsessions) and/or repetitive behaviors or mental acts that the person feels driven to perform (compulsions). OCD has a partly genetic basis. For treatment of OCD, potent serotonin reuptake inhibitor (SRI) drugs (clomipramine (Anafranil), fluvoxamine (Luvox), fluoxetine (Prozac), sertraline (Zoloft), and paroxetine (Paxil)), which act on the serotonin transporter protein, are uniquely efficacious. A polymorphism in the promoter region of the gene (SLC6A4) encoding this protein, was recently reported to affect protein expression and to be associated with measures of anxiety and depression and with autism (using a family-controlled transmission disequilibrium test (TDT) design). SLC6A4 therefore has strong a priori support for potentially influencing risk for OCD: the protein it encodes is a medication target; a polymorphism in the gene affects function; and that polymorphism has been shown to be associated with behavioral phenotypes. We used the TDT with a set of 34 European-American family trios, 30 unrelated and four drawn from an extended pedigree, to test for linkage disequilibrium between OCD and alleles at the SLC6A4 promoter polymorphic locus. Of 35 heterozygous parents, 24 transmitted the 'l' SLC6A4 allele and 11 transmitted the 's' allele (chi 2 TDT = 4.83; P < 0.03). Considering only the 13 SRI drug nonresponders, there were 13 heterozygous parents, of whom 10 transmitted the 'l' allele and three the 's' allele (chi 2 TDT = 3.77; P < 0.052). These data provide preliminary support for association and linkage disequilibrium between the SLC6A4 'l' allele and OCD.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9672904&dopt=Abstract
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inst.hospvd.ch
A gas chromatography-mass spectrometry method is presented which allows the simultaneous determination of the plasma concentrations of the selective serotonin reuptake inhibitors citalopram, paroxetine, sertraline, and their pharmacologically active N-demethylated metabolites (desmethylcitalopram, didesmethylcitalopram, and desmethylsertraline) after derivatization with the reagent N-methyl-bis(trifluoroacetamide). No interferences from endogenous compounds are observed following the extraction of plasma samples from six different human subjects. The standard curves are linear over a working range of 10-500 ng/mL for citalopram, 10-300 ng/mL for desmethylcitalopram, 5-60 ng/mL for didesmethylcitalopram, 20-400 ng/mL for sertraline and desmethylsertraline, and 10-200 ng/mL for paroxetine. Recoveries measured at three concentrations range from 81 to 118% for the tertiary amines (citalopram and the internal standard methylmaprotiline), 73 to 95% for the secondary amines (desmethylcitalopram, paroxetine and sertraline), and 39 to 66% for the primary amines (didesmethylcitalopram and desmethylsertraline). Intra- and interday coefficients of variation determined at three concentrations range from 3 to 11% for citalopram and its metabolites, 4 to 15% for paroxetine, and 5 to 13% for sertraline and desmethylsertraline. The limits of quantitation of the method are 2 ng/mL for citalopram and paroxetine, 1 ng/mL for sertraline, and 0.5 ng/mL for desmethylcitalopram, didesmethylcitalopram, and desmethylsertraline. No interferences are noted from 20 other psychotropic drugs. This sensitive and specific method can be used for single-dose pharmacokinetics. It is also useful for therapeutic drug monitoring of these three drugs and could possibly be adapted for the quantitation of the two other selective serotonin reuptake inhibitors on the market, namely fluoxetine and fluvoxamine.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9679303&dopt=Abstract
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