Synthesis and pharmacological characterization of bivalent ligands of epibatidine at neuronal nicotinic acetylcholine receptors.
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.
Wei
Zhi-Liang
ZL
Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, 833 S. Wood Street, Chicago, IL 60612, USA.
Xiao
Yingxian
Y
Kellar
Kenneth J
KJ
Kozikowski
Alan P
AP
D000818:Animals; D001667:Binding, Competitive; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000138:chemical synthesis* / Q000494:pharmacology*; D008024:Ligands; D015394:Molecular Structure; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D009538:Nicotine / Q000494:pharmacology; D011725:Pyridines / Q000138:chemical synthesis* / Q000494:pharmacology*; D051381:Rats; D011978:Receptors, Nicotinic / Q000187:drug effects* / Q000378:metabolism; D013329:Structure-Activity Relationship
D019086:Bridged Bicyclo Compounds, Heterocyclic; D008024:Ligands; D011725:Pyridines; D011978:Receptors, Nicotinic; C403530:nicotinic receptor alpha3beta4; D009538:Nicotine; C082748:epibatidine