Epibatidine analogues as selective ligands for the alpha(x)beta2-containing subtypes of nicotinic acetylcholine receptors.
A series of epibatidine analogues was synthesized and characterized in vitro. These compounds are high affinity ligands for the nicotinic acetylcholine receptors (nAChR). They display binding selectivity for the alpha(x)beta2 subtypes of nAChRs over the alpha(x)beta4 subtypes, and especially for the alpha4beta2 and alpha2beta2 subtypes. Furthermore, most of these new nicotinic compounds display little, if any, agonist activities at alpha3beta4 nAChR. As a result they might become lead structures for the design and synthesis of highly selective ligands for nAChR subtypes containing the beta2 subunit.
Huang
Yiyun
Y
Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA. hh285@columbia.edu
Zhu
Zhihong
Z
Xiao
Yingxian
Y
Laruelle
Marc
M
D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D002460:Cell Line; D006801:Humans; D008024:Ligands; D018722:Nicotinic Agonists / Q000138:chemical synthesis*; D011725:Pyridines / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D011869:Radioligand Assay; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000378:metabolism*; D013329:Structure-Activity Relationship; D014162:Transfection
D019086:Bridged Bicyclo Compounds, Heterocyclic; D008024:Ligands; D018722:Nicotinic Agonists; D011725:Pyridines; D011978:Receptors, Nicotinic; C082748:epibatidine