Abstract
N-n-Alkylation of nicotine converts it from an agonist into an antagonist at neuronal nicotinic acetylcholine receptor subtypes mediating nicotine-evoked dopamine release. Conformationally restricted analogues exhibit both high affinity and selectivity at this site, and are able to access the brain due to their ability to act as substrates for the blood-brain barrier choline transporter.
MeSH terms
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Aconitine / analogs & derivatives*
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Aconitine / antagonists & inhibitors
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Aconitine / metabolism
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Animals
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Binding Sites
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Binding, Competitive / drug effects
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Brain / drug effects
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Brain / metabolism
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Choline / antagonists & inhibitors
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Choline / metabolism
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Dopamine / metabolism*
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Ligands
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Male
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Molecular Structure
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Nicotine / antagonists & inhibitors
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Nicotine / metabolism
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Nicotine / pharmacology
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Nicotinic Antagonists / chemistry*
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Nicotinic Antagonists / pharmacology*
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Rats
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Rats, Sprague-Dawley
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Receptors, Nicotinic / drug effects*
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Receptors, Nicotinic / metabolism
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Structure-Activity Relationship
Substances
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Ligands
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Nicotinic Antagonists
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Receptors, Nicotinic
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methyllycaconitine
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Nicotine
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Choline
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Dopamine
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Aconitine