Allosteric modifiers of neuronal nicotinic acetylcholine receptors: new methods, new opportunities

Med Res Rev. 2007 Sep;27(5):723-53. doi: 10.1002/med.20091.


Allosteric, non-competitive inhibitors (NCIs) of neuronal nicotinic acetylcholine receptors (nAChRs) have been shown to produce a wide variety of clinically relevant responses. Many of the observed effects are desired as the nAChR is the therapeutic target, while others are undesired consequences due to off-target binding at the nAChR. Thus, the determination of whether or not a lead drug candidate is an NCI should play an important role in drug discovery programs. However, the current experimental techniques used to identify NCIs are challenging, expensive, and time consuming. This review focuses on an alternative approach to the investigation of interactions between test compounds and nAChRs based upon liquid chromatographic stationary phases containing cellular fragments from cell lines expressing nAChRs. The development and validation of these phases as well as their use in drug discovery and pharmacophore modeling are discussed.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Review

MeSH terms

  • Allosteric Regulation
  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Humans
  • Models, Biological
  • Models, Molecular
  • Molecular Sequence Data
  • Nicotinic Antagonists / chemical synthesis
  • Nicotinic Antagonists / chemistry*
  • Nicotinic Antagonists / metabolism
  • Receptors, Nicotinic / chemistry*
  • Receptors, Nicotinic / metabolism
  • Sequence Alignment


  • Nicotinic Antagonists
  • Receptors, Nicotinic