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

Guangrong Zheng, Zhenfa Zhang, Cheryl Dowell, Elzbieta Wala, Linda P. Dwoskin, Joseph R. Holtman, J. Michael McIntosh, Peter A. Crooks

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)2476-2479
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Volume21
Issue number8
DOIs
StatePublished - Apr 15 2011

Bibliographical note

Funding Information:
This work was supported by NIH (Grant U19DA017548 to L.P.D. and P.A.C., MH53631 and GM48677 to J.M.M.) and a seed grant from the University of Utah Research Foundation to J.M.M.

Keywords

  • Analgesic
  • Pain
  • SAR
  • α9α10 nAChR

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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