Drugs online research references
Psychopharmacol Bull. 1995;31(2):339-45.
Lymphocyte glucocorticoid receptor: predictor of sertraline response in adolescent major depressive disorder (MDD).
Sallee FR, Nesbitt L, Dougherty D, Hilal R, Nandagopal VS, Sethuraman G.
Department of Psychiatry and Pharmacology, Medical University of South Carolina, Charleston 29425, USA.
Major depressive disorder (MDD) in adolescents demonstrates resistance to tricyclic antidepressants and absence of hypercortisolemia. The efficacy of serotonin reuptake inhibitors (SRIs) is uncertain, and response predictors are unavailable. Abnormal fast feedback and negative feedback of the hypothalamic-pituitary-adrenal axis implicates a dampened limbic-hippocampal glucocorticoid type II receptor (GCII). We hypothesized that lymphocyte GCII is altered in adolescent MDD and could serve as a marker for response to SRIs. In an open-label study, adolescents (n = 20) meeting DSM-III-R criteria for MDD showed baseline lymphocyte GCII sites per cell (sites/cell) values of 793 +/- 106 versus 2,563 +/- 499 (+/- SEM) for matched controls (n = 18) (t = 3.5; df = 36; p < .001). GCII was bimodally distributed, with SRI responders differing from nonresponders (t = 3.9; df = 14; p < .001). GCII accurately classified 90 percent of sertraline responders and 80 percent of nonresponders. Only SRI responders showed GCII sites/cell upregulated after 6 weeks of treatment (t = 2.1, df = 10; p < .05).
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7491389&dopt=Abstract
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Neuropharmacology. 1994 Aug;33(8):1011-6.
The effect of tianeptine and sertraline in three animal models of depression.
Kelly JP, Leonard BE.
Department of Pharmacology, University College, Galway, Ireland.
The activity of tianeptine (2.5 and 5.0 mg/kg twice daily, i.p.) and of sertraline (5.0 mg/kg, twice daily, i.p.) were assessed in three animal models of depression. In the Behavioural Despair Test, acute treatment with sertraline or tianeptine (5.0 mg/kg) significantly reduced the immobility time. In the olfactory bulbectomized (OB) rat model, chronic treatment with tianeptine (2.5 and 5.0 mg/kg) or sertraline (5.0 mg/kg) antagonized the lesion-induced hyperactivity in the "open field" apparatus. The hypothermic response to the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT, 0.15 mg/kg, s.c.) was significantly attenuated after chronic setraline treatment, whereas tianeptine was inactive at the 2 doses tested. Neither drug affected the hypersection of corticosterone that occurs at the light:dark interface. A reduction in the serotonin metabolite 5-HIAA was found in the hypothalamus of sertraline-treated sham rats. It can be concluded that although the neurochemical properties of sertraline and tianeptine differ, they demonstrate similar antidepressant-like activities in the Behavioural Despair and OB rat models. The lack of effect of tianeptine on the 8-OH-DPAT-induced hypothermic effect indicates that it does not induce 5-HT1A subsensitivity, contrary to most antidepressants.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7531300&dopt=Abstract
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Prog Neuropsychopharmacol Biol Psychiatry. 1995 Jan;19(1):135-49.
Comparison of desmethylsertraline with sertraline as a monoamine uptake inhibitor in vivo.
Fuller RW, Hemrick-Luecke SK, Littlefield ES, Audia JE.
Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, USA.
1. Desmethylsertraline, a metabolite of the antidepressant drug sertraline, was compared with sertraline for its ability to produce effects characteristic of inhibitors of the serotonin transporter in vivo. Desmethylsertraline antagonized brain serotonin depletion by p-chloroamphetamine, a depletion dependent upon the serotonin transporter, being less potent than sertraline in rats but almost as potent as sertraline in mice. Desmethylsertraline was a weak antagonist of 6-hydroxydopamine-induced depletion of heart norepinephrine in mice; sertraline had no effect at the doses studied. 2. Desmethylsertraline decreased brain concentrations of 5-hydroxyindoleacetic acid (5HIAA) in rats as did sertraline, the duration of the effect after both drugs being at least 24 hrs but less than 48 hrs. 3. After sertraline injection, desmethylsertraline was present in rat brain at higher concentrations than the parent drug at 8 hrs and thereafter. 4. In rats, repeated injections of sertraline, at doses previously shown to diminish beta-adrenergic receptor-mediated responses, led to marked accumulation of desmethylsertraline in brain and to inhibition of the catecholamine transporters. 5. In mice, brain concentrations of desmethylsertraline were higher than those of parent drug within 7 hrs after sertraline injection and probably contributed importantly to the antagonism of p-chloroamphetamine effects. 6. These data show that desmethylsertraline is less potent than sertraline as a serotonin uptake inhibitor in vivo, as the in vitro data would have predicted, but that desmethylsertraline may nonetheless contribute to the prolonged inhibition of the serotonin transporter after sertraline administration, perhaps more in mice than in rats.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7535937&dopt=Abstract
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