Abstract
Antagonist activity at the α3β4 nicotinic acetylcholine receptor (nAChR) is thought to contribute to the antiaddictive properties of several compounds. However, truly selective ligands for the α3β4 nAChR have not been available. We report the discovery and SAR of a novel class of compounds that bind to the α3β4 nAChR and have no measurable affinity for the α4β2 or α7 subtype. In functional assays the lead compound antagonized epibatidine-induced Ca(2+) flux in α3β4-transfected cells in a noncompetitive manner.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Azabicyclo Compounds / chemical synthesis*
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Azabicyclo Compounds / chemistry
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Azabicyclo Compounds / pharmacology
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Bridged Bicyclo Compounds, Heterocyclic / pharmacology
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Cell Line
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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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Ligands
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Nicotinic Agonists / 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 / pharmacology
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Receptors, Nicotinic / genetics
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Receptors, Nicotinic / metabolism*
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Structure-Activity Relationship
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Transfection
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alpha7 Nicotinic Acetylcholine Receptor
Substances
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1-(9-methyl-9-azabicyclo(3.3.1)non-3-yl)-1,3-dihydro-2H-indol-2-one
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Azabicyclo Compounds
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Bridged Bicyclo Compounds, Heterocyclic
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Chrna7 protein, human
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Indoles
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Ligands
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Nicotinic Agonists
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Nicotinic Antagonists
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Pyridines
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Receptors, Nicotinic
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alpha7 Nicotinic Acetylcholine Receptor
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nicotinic receptor alpha3beta4
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nicotinic receptor alpha4beta2
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epibatidine