Subtype-selective nicotinic receptor antagonists: potential as tobacco use cessation agents.
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.
Dwoskin
Linda P
LP
Division of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536-0082, USA. ldwoskin@uky.edu
Sumithran
Sangeetha P
SP
Zhu
Jun
J
Deaciuc
A Gabriela
AG
Ayers
Joshua T
JT
Crooks
Peter A
PA
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
D018733:Nicotinic Antagonists; D010847:Picolines; D011978:Receptors, Nicotinic; D009538:Nicotine