Tetrakis-azaaromatic quaternary ammonium salts: Novel subtype-selective antagonists at neuronal nicotinic receptors that mediate nicotine-evoked dopamine release

Zhenfa Zhang, Guangrong Zheng, Marharyta Pivavarchyk, A. Gabriela Deaciuc, Linda P. Dwoskin, Peter A. Crooks

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

A series of tetrakis-azaaromatic quaternary ammonium salts was synthesized to identify compounds with higher affinity and selectivity as antagonists at neuronal nicotinic receptor subtypes (nAChR) that mediate nicotine-evoked DA release. A high hit rate was achieved in identifying potent analogs that inhibit these nAChRs. Three tetrakis analogs, 11j, 11f, and 11g, were identified as potent (IC50 = 3, 28 and 56 nM, respectively) antagonists at these receptors. These compounds represent a novel structural class of nicotinic receptor antagonists.

Original languageEnglish
Pages (from-to)5753-5757
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Volume18
Issue number21
DOIs
StatePublished - Nov 1 2008

Bibliographical note

Funding Information:
This research was supported by NIH Grant U19DA017548.

Keywords

  • Dopamine release
  • Nicotine addiction
  • Nicotinic acetylcholine receptor
  • Quaternary ammonium

ASJC Scopus subject areas

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

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