Abstract
A series of conformationally restricted bis-azaaromatic quaternary ammonium salts (3 and 4) have been designed and synthesized in order to investigate the possible binding conformations of N,N'-dodecane-1,12-diyl-bis-3-picolinium dibromide (bPiDDB; 2), a compound which potently inhibits neuronal nicotinic acetylcholine receptors (nAChRs) mediating nicotine-evoked dopamine release. The preliminary structure-activity relationships of these new analogues suggest that bPiDDB binds in an extended conformation at the nAChR binding site, and that flexibility of the linker may be important for its high potency in inhibiting nAChRs mediating nicotine-evoked dopamine release.
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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Combinatorial Chemistry Techniques
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Dopamine / metabolism*
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Models, Molecular
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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 / chemical synthesis*
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Quaternary Ammonium Compounds / chemistry
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Quaternary Ammonium Compounds / pharmacology*
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Rats
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Receptors, Nicotinic / metabolism*
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Salts / chemical synthesis
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Salts / chemistry
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Salts / pharmacology
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Structure-Activity Relationship
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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Nicotine
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Dopamine