Abstract
A series of tris-azaaromatic quaternary ammonium salts has been synthesized and evaluated for their ability to inhibit neuronal nicotinic acetylcholine receptors (nAChRs) mediating nicotine-evoked [(3)H]dopamine release from superfused rat striatal slices and for inhibition of [(3)H]nicotine and [(3)H]methyllycaconitine binding to whole rat brain membranes. The 3-picolinium compound 1,3,5-tri-{5-[1-(3-picolinium)]-pent-1-ynyl}benzene tribromide (tPy3PiB), 3b, exhibited high potency and selectivity for nAChR subtypes mediating nicotine-evoked [(3)H]dopamine release with an IC(50) of 0.2 nM and I(max) of 67%.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Animals
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Aza Compounds / chemical synthesis*
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Aza Compounds / chemistry
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Aza Compounds / pharmacology*
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Brain / drug effects
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Brain / metabolism
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Dopamine / metabolism
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Molecular Structure
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Nicotine / metabolism*
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Nicotinic Antagonists / chemical synthesis*
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Nicotinic Antagonists / chemistry
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Nicotinic Antagonists / pharmacology*
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Quaternary Ammonium Compounds / chemistry*
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Rats
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Receptors, Nicotinic / metabolism*
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Salts / chemistry
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Structure-Activity Relationship
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Tromethamine / chemistry
Substances
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Aza Compounds
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Nicotinic Antagonists
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Quaternary Ammonium Compounds
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Receptors, Nicotinic
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Salts
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Tromethamine
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Nicotine
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Dopamine