Abstract
A small series of aryl pyridyl sulfones has been prepared and investigated for its 5-HT(6) receptor binding properties. Thereof, pyrrolidinyl derivative 11 proved to be a very potent (pK(i) 9) and selective 5-HT(6) receptor antagonist. By means of in vivo microdialysis in the frontal cortex and a passive avoidance paradigm, where 11 reversed a scopolamine induced retention deficit, a functional correlation between 5-HT(6) receptors and cholinergic neurotransmission could be shown, supporting the therapeutic potential of 5-HT(6) receptors in the treatment of cognitive deficits.
MeSH terms
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Acetylcholine / metabolism*
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Administration, Oral
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Animals
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Avoidance Learning / drug effects
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Biological Availability
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Blood-Brain Barrier
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Cell Line
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Frontal Lobe / drug effects*
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Frontal Lobe / metabolism
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Half-Life
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Humans
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In Vitro Techniques
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Injections, Intravenous
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Microdialysis
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Microsomes, Liver / metabolism
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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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Receptors, Serotonin / drug effects*
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Receptors, Serotonin / physiology
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Serotonin Antagonists / chemical synthesis*
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Serotonin Antagonists / chemistry
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Serotonin Antagonists / pharmacology
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Sulfones / chemical synthesis*
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Sulfones / chemistry
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Sulfones / pharmacology
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Tissue Distribution
Substances
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4-(2-bromo-6-pyrrolidin-1-ylpyridine-4-sulfonyl)phenylamine
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Pyridines
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Receptors, Serotonin
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Serotonin Antagonists
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Sulfones
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serotonin 6 receptor
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Acetylcholine