Abstract
A series of tertiary amine analogs derived from lead azaaromatic quaternary ammonium salts has been designed and synthesized. The preliminary structure-activity relationships of these new analogs suggest that such tertiary amine analogs, which potently inhibit nicotine-evoked dopamine release from rat striatum, represent drug-like inhibitors of α6-containing nicotinic acetylcholine receptors. The bis-tertiary amine analog 7 exhibited an IC(50) of 0.95 nM, while the tris-tertiary amine analog 19 had an IC(50) of 0.35 nM at nAChRs mediating nicotine-evoked dopamine release.
Copyright © 2010 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Amines / chemical synthesis
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Amines / chemistry*
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Amines / pharmacology
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Animals
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Dopamine / metabolism*
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Isoquinolines / chemical synthesis
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Isoquinolines / chemistry*
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Isoquinolines / pharmacology
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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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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, Nicotinic / chemistry*
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Receptors, Nicotinic / metabolism
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Structure-Activity Relationship
Substances
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Amines
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Isoquinolines
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Nicotinic Antagonists
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Pyridines
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Receptors, Nicotinic
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Dopamine