title: Subtype-selective nicotinic receptor antagonists: potential as tobacco use cessation agents.
abstract: N-n-Alkylpicolinium and N,N'-alkyl-bis-picolinium analogues were assessed in nicotinic receptor (nAChR) assays. The most potent and subtype-selective analogue, N,N'-dodecyl-bis-picolinium bromide (bPiDDB), inhibited nAChRs mediating nicotine-evoked [(3)H]dopamine release (IC(50)=5 nM; I(max) of 60%), and did not interact with alpha4beta2* or alpha7* nAChRs. bPiDDB represents the current lead compound for development as a tobacco use cessation agent.
authors.affiliation: Division of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536-0082, USA. ldwoskin@uky.edu
authors.forename: Linda P
authors.initials: LP
authors.lastname: Dwoskin
authors.forename: Sangeetha P
authors.initials: SP
authors.lastname: Sumithran
authors.forename: Jun
authors.initials: J
authors.lastname: Zhu
authors.forename: A Gabriela
authors.initials: AG
authors.lastname: Deaciuc
authors.forename: Joshua T
authors.initials: JT
authors.lastname: Ayers
authors.forename: Peter A
authors.initials: PA
authors.lastname: Crooks
mesh_terms: D000818:Animals; D001681:Biological Assay; D008297:Male; D015394:Molecular Structure; D009538:Nicotine / Q000494:pharmacology; D018733:Nicotinic Antagonists / Q000737:chemistry / Q000494:pharmacology*; D010847:Picolines / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000187:drug effects* / Q000378:metabolism; D016540:Smoking Cessation; D013329:Structure-Activity Relationship
chemical_list: D018733:Nicotinic Antagonists; D010847:Picolines; D011978:Receptors, Nicotinic; D009538:Nicotine