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• W2018018132 abstract "Specific binding of [3H]imipramine to its recognition sites in frontal cortex and levels of serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA) and norepinephrine (NE) as well as uptake of serotonin by crude synaptosomal (P2) fraction were determined in a group of rats chronically (for 21 days) treated with different types of antidepressant drugs: nortriptyline, fluoxetine, iprindole, phenelzine (10 mg/kg per day), maprotiline (20 mg/kg per day) and vehicle only (controls). Quantitative analysis of imipramine competition curves confirmed the existence of two classes of [3H]imipramine sites: high-affinity with IC50 and 11.2 nM and low-affinity with IC50 of 630 nM for the competing ligand. The proportion of high- and low-affinity sites was 73 +/- 4 and 26 +/- 4%, respectively. Chronic treatment with all antidepressant drugs except iprindole significantly decreased the affinity but not the proportion of high-affinity sites for imipramine. IC50 of imipramine at low-affinity sites was even more markedly increased at low-affinity sites by all treatments except for phenelzine. Fluoxetine was by far the most effective in altering the affinity of both high- and low-affinity [3H]imipramine recognition sites. Both NE and 5-HT levels were significantly enhanced only by phenelzine treatment, whereas 5-HT and 5-HIAA levels were found to be lower after fluoxetine. Kinetics of 5-HT uptake were altered significantly only in rats treated with fluoxetine: rate of 5-HT uptake (Vmax) was decreased by 43% and Km value increased from 104 to 184 nM. Changes in affinity of imipramine for its binding sites were not found to be associated with the effect of tested drugs on 5-HT levels or uptake. They may be due to adaptive alterations in physico-chemical properties of binding proteins although the presence of residual drug interfering with the binding assay cannot be excluded. The observed changes are likely to represent the condition during chronic administration of these drugs in clinical therapy of depression." @default.
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• W2018018132 date "1987-06-01" @default.
• W2018018132 modified "2023-09-27" @default.
• W2018018132 title "Regulation of high- and low-affinity [3H]imipramine recognition sites in rat brain by chronic treatment with antidepressants" @default.
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• W2018018132 doi "https://doi.org/10.1016/0014-2999(87)90429-8" @default.
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