Abstract
A series of indole tetrahydropyridine and indole cyclohexenylamines was prepared, and their binding affinities at the human serotonin transporter (SERT) were determined. In particular, a nitrile substituent at the C5 position of the indole ring gave potent SERT activity. The stereochemistry of the N,N-dimethylamine substituent was determined for the most potent indole cyclohexenylamine, 6a. The enantiomers of 6a were energy minimized and compared to other conformationally restricted SSRIs. Compound 6a was found to give a dose-response similar to the SSRI fluoxetine in microdialysis studies in rats.
MeSH terms
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Animals
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Cyclohexenes / chemical synthesis
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Cyclohexenes / chemistry
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Cyclohexenes / pharmacology
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Fluoxetine / chemistry
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Fluoxetine / pharmacology
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Humans
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Indoles / chemical synthesis
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Indoles / chemistry
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Indoles / pharmacology
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Microdialysis
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Molecular Conformation
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Pyridines / chemical synthesis
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Pyridines / chemistry
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Pyridines / pharmacology
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Rats
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Selective Serotonin Reuptake Inhibitors / chemical synthesis
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Selective Serotonin Reuptake Inhibitors / chemistry*
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Selective Serotonin Reuptake Inhibitors / metabolism*
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Serotonin Plasma Membrane Transport Proteins / metabolism*
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Tryptamines / chemistry*
Substances
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Cyclohexenes
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Indoles
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Pyridines
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SLC6A4 protein, human
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Serotonin Plasma Membrane Transport Proteins
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Serotonin Uptake Inhibitors
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Tryptamines
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Fluoxetine