Abstract
In vitro radioligand binding studies were carried out in rat brain membranes to assess the affinity of various reuptake inhibitors for the serotonin (5-hydroxytryptamine, 5-HT) and the norepinephrine transporters using the selective ligands [3H]cyanoimipramine and [3H]nisoxetine, respectively. The selective 5-HT reuptake inhibitors paroxetine, indalpine and fluvoxamine displayed a high affinity for the 5-HT transporter, whereas the norepinephrine reuptake inhibitor desipramine had a high affinity for the norepinephrine transporter. Duloxetine, a dual 5-HT and norepinephrine reuptake inhibitor, displayed a high affinity for both the 5-HT and the norepinephrine transporters. Interestingly, venlafaxine, a dual 5-HT and norepinephrine reuptake inhibitor, displayed only a moderate affinity for the 5-HT transporter (Ki = 74 nM) and a very low affinity for the norepinephrine transporter (Ki = 1.26 microM). The relatively low affinities of venlafaxine contrast with its potent in vivo 5-HT and norepinephrine reuptake blocking properties. These results raise the possibility that the in vivo effects on the 5-HT and norepinephrine reuptake observed with venlafaxine may not be mediated solely by its binding to the [3H]cyanoimipramine and [3H]nisoxetine binding sites.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antidepressive Agents, Second-Generation / metabolism*
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Binding, Competitive
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Brain / metabolism
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Carrier Proteins / metabolism*
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Cyclohexanols / metabolism*
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Fluoxetine / analogs & derivatives
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Fluoxetine / metabolism
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Imipramine / analogs & derivatives
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Imipramine / metabolism
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Male
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Membrane Glycoproteins / metabolism*
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Membrane Transport Proteins*
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Nerve Tissue Proteins*
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Neurotransmitter Uptake Inhibitors / metabolism*
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Norepinephrine / antagonists & inhibitors
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Norepinephrine / metabolism*
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Norepinephrine Plasma Membrane Transport Proteins
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Radioligand Assay
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Rats
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Rats, Sprague-Dawley
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Selective Serotonin Reuptake Inhibitors / metabolism
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Serotonin / metabolism*
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Serotonin Antagonists / metabolism
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Serotonin Plasma Membrane Transport Proteins
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Symporters*
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Venlafaxine Hydrochloride
Substances
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Antidepressive Agents, Second-Generation
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Carrier Proteins
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Cyclohexanols
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Membrane Glycoproteins
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Membrane Transport Proteins
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Nerve Tissue Proteins
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Neurotransmitter Uptake Inhibitors
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Norepinephrine Plasma Membrane Transport Proteins
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Serotonin Antagonists
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Serotonin Plasma Membrane Transport Proteins
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Serotonin Uptake Inhibitors
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Slc6a2 protein, rat
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Slc6a4 protein, rat
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Symporters
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Fluoxetine
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cianopramine
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nisoxetine
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Serotonin
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Venlafaxine Hydrochloride
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Imipramine
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Norepinephrine