title: Development of subtype-selective ligands as antagonists at nicotinic receptors mediating nicotine-evoked dopamine release.
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.
authors.affiliation: Division of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536-0082, USA. pcrooks@uky.edu
authors.forename: Peter A
authors.initials: PA
authors.lastname: Crooks
authors.forename: Joshua T
authors.initials: JT
authors.lastname: Ayers
authors.forename: Rui
authors.initials: R
authors.lastname: Xu
authors.forename: Sangeetha P
authors.initials: SP
authors.lastname: Sumithran
authors.forename: Vladimir P
authors.initials: VP
authors.lastname: Grinevich
authors.forename: Lincoln H
authors.initials: LH
authors.lastname: Wilkins
authors.forename: A Gabriela
authors.initials: AG
authors.lastname: Deaciuc
authors.forename: David D
authors.initials: DD
authors.lastname: Allen
authors.forename: Linda P
authors.initials: LP
authors.lastname: Dwoskin
mesh_terms: D000157:Aconitine / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002794:Choline / Q000037:antagonists & inhibitors / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D008024:Ligands; D008297:Male; D015394:Molecular Structure; D009538:Nicotine / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology; D018733:Nicotinic Antagonists / Q000737:chemistry* / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000187:drug effects* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D008024:Ligands; D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; C054634:methyllycaconitine; D009538:Nicotine; D002794:Choline; D004298:Dopamine; D000157:Aconitine