Drugs online research references
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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Pharmacol Biochem Behav. 1999 Apr;62(4):695-701.
Chronic fluoxetine in tests of anxiety in rat lines selectively bred for differential 5-HT1A receptor function.
File SE, Ouagazzal AM, Gonzalez LE, Overstreet DH.
Psychopharmacology Research Unit, Neuroscience Research Centre, GKT School of Biomedical Sciences, King's College London, UK.
Selective breeding for high and low sensitivity to the hypothermic response induced by the 5-HT1A receptor agonist 8- OH-DPAT has established two lines of rat (HDS and LDS, respectively) whose behavior differs in a model of depression and in the social interaction test of anxiety. The HDS line has a higher level of anxiety and, furthermore, does not display the usual anxiogenic response to intrahippocampal administration of 8-OH-DPAT. It was therefore hypothesized that this line of rat might be a useful model of high trait anxiety with a susceptibility to depression. We thus investigated whether chronic treatment with fluoxetine would result in an anxiolytic effect in the social interaction test in the LDS and HDS lines of rat. In both lines, acute fluoxetine (10 mg/kg) produced an anxiogenic effect in the social interaction test; when rats were tested 24 h after 14 days of fluoxetine treatment there were no anxiolytic effects in either line. In the social interaction test, chronic fluoxetine treatment did not change either the anxiogenic effect of 8-OH-DPAT (100 ng) injected bilaterally into the dorsal hippocampus in the LDS line or the lack of response in the HDS line. In the elevated plus-maze, chronic fluoxetine treatment resulted in a significant anxiogenic effect in the HDS line, but was without effect in the LDS line. Intrahippocampal 8-OH-DPAT was without effect in the plus-maze in either line. These results suggest that chronic treatment with fluoxetine did not modify the hippocampal 5-HT1A receptor in either line. The anxiogenic effects observed in the plus-maze in the HDS line after chronic fluoxetine might relate to line differences in 5-HT1A receptors in other brain regions.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10208375&dopt=Abstract
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Life Sci. 1998;63(2):PL31-8.
Effects of fluoxetine on the development of lung metastases induced by operative stress in rats.
Freire-Garabal M, Nunez MJ, Pereiro D, Riveiro P, Losada C, Fernandez-Rial JC, Garcia-Iglesias E, Prizmic J, Mayan JM, Rey-Mendez M.
Department of Pharmacology, University of Santiago de Compostela, Spain.
Experiments were performed in order to evaluate the effects of fluoxetine, a selective inhibitor of neural serotonin transporter antidepressant, on the development lung metastases in rats subjected to laparotomy and injected (i.v.) with 10(4) Walker 256 (W-256) carcinosarcoma cells. The number of metastatic nodules on the surface of the lungs, as well as the percentage-area of metastases in the frontal section through pulmonary hilus were increased in rats subjected to sham-surgery or laparotomy. Treatment with fluoxetine (5 mg/kg) partially reversed those adverse effects of surgery, but the difference was clearer when it was administered before surgery was performed. Survival periods were also assessed and fluoxetine was found to decrease the lethality of rats exposed to surgery.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9674952&dopt=Abstract
note: kwd match prozac online literature
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