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 [ 3H]dopamine release (IC 50=5 nM; I max of 60%), and did not interact with α4β2* or α7* nAChRs. bPiDDB represents the current lead compound for development as a tobacco use cessation agent. 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 [ 3H]dopamine release (IC 50=5 nM; I max of 60%), and did not interact with α4β2* or a7* nAChRs.