Discovery of non-peptide, small molecule antagonists of α9α10 nicotinic acetylcholine receptors as novel analgesics for the treatment of neuropathic and tonic inflammatory pain

Bioorg Med Chem Lett. 2011 Apr 15;21(8):2476-9. doi: 10.1016/j.bmcl.2011.02.043. Epub 2011 Feb 23.


A series of azaaromatic quaternary ammonium analogs has been discovered as potent and selective α9α10 nicotinic acetylcholine receptor (nAChR) antagonists. The preliminary structure-activity relationships of these analogs suggest that increased rigidity in the linker units results in higher potency in inhibition of α9α10 nAChRs and greater selectivity over α7 nAChRs. These analogs represent a new class of analgesic for the treatment of neuropathic and tonic inflammatory pain.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analgesics / chemical synthesis
  • Analgesics / chemistry*
  • Analgesics / therapeutic use
  • Animals
  • Drug Evaluation, Preclinical
  • Nicotinic Antagonists / chemical synthesis
  • Nicotinic Antagonists / chemistry*
  • Nicotinic Antagonists / therapeutic use
  • Pain / drug therapy*
  • Quaternary Ammonium Compounds / chemical synthesis
  • Quaternary Ammonium Compounds / chemistry
  • Quaternary Ammonium Compounds / therapeutic use
  • Rats
  • Receptors, Nicotinic / chemistry*
  • Receptors, Nicotinic / metabolism
  • Structure-Activity Relationship


  • Analgesics
  • Chrna10 protein, rat
  • Chrna9 protein, rat
  • Nicotinic Antagonists
  • Quaternary Ammonium Compounds
  • Receptors, Nicotinic