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.