Subtype-selective nicotinic receptor antagonists: potential as tobacco use cessation agents

Bioorg Med Chem Lett. 2004 Apr 19;14(8):1863-7. doi: 10.1016/j.bmcl.2003.10.073.

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Biological Assay
  • Male
  • Molecular Structure
  • Nicotine / pharmacology
  • Nicotinic Antagonists / chemistry
  • Nicotinic Antagonists / pharmacology*
  • Picolines / chemistry
  • Picolines / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Nicotinic / drug effects*
  • Receptors, Nicotinic / metabolism
  • Smoking Cessation*
  • Structure-Activity Relationship

Substances

  • Nicotinic Antagonists
  • Picolines
  • Receptors, Nicotinic
  • Nicotine