Synthesis and pharmacological characterization of bivalent ligands of epibatidine at neuronal nicotinic acetylcholine receptors

Zhi-Liang Wei; Yingxian Xiao; Kenneth J Kellar; Alan P Kozikowski

doi:10.1016/j.bmcl.2003.10.071

Synthesis and pharmacological characterization of bivalent ligands of epibatidine at neuronal nicotinic acetylcholine receptors

Bioorg Med Chem Lett. 2004 Apr 19;14(8):1855-8. doi: 10.1016/j.bmcl.2003.10.071.

Authors

Zhi-Liang Wei¹, Yingxian Xiao, Kenneth J Kellar, Alan P Kozikowski

Affiliation

¹ Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, 833 S. Wood Street, Chicago, IL 60612, USA.

PMID: 15050615
DOI: 10.1016/j.bmcl.2003.10.071

Abstract

A series of bivalent ligands 6a-d of epibatidine were synthesized. All four ligands showed nanomolar binding affinities at six neuronal nicotinic acetylcholine receptor (nAChR) subtypes in competition binding assays. In contrast to epibatidine, these bivalent ligands are weak partial agonists at the alpha3beta4 nAChR as shown by functional assays.

Publication types

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

MeSH terms

Animals
Binding, Competitive
Bridged Bicyclo Compounds, Heterocyclic / chemical synthesis*
Bridged Bicyclo Compounds, Heterocyclic / pharmacology*
Ligands
Molecular Structure
Neurons / drug effects*
Neurons / metabolism
Nicotine / pharmacology
Pyridines / chemical synthesis*
Pyridines / pharmacology*
Rats
Receptors, Nicotinic / drug effects*
Receptors, Nicotinic / metabolism
Structure-Activity Relationship

Substances

Bridged Bicyclo Compounds, Heterocyclic
Ligands
Pyridines
Receptors, Nicotinic
nicotinic receptor alpha3beta4
Nicotine
epibatidine

Grants and funding

R01 DA 17980/DA/NIDA NIH HHS/United States