Norchloro-fluoro-homoepibatidine: specificity to neuronal nicotinic acetylcholine receptor subtypes in vitro.
The subtype-specificity of newly synthesised epibatidine-related compounds, norchloro-fluoro-homoepibatidine (NCFHEB) and derivatives, to neuronal nicotinic acetylcholine receptors (nAChR) has been investigated. NCFHEBs were assayed in competitive binding assays to (+/-)-[(3)H]epibatidine-labelled rat thalamic nAChRs and human alpha4beta2, alpha3beta4, and alpha7 nAChRs, expressed in stably transfected HEK-293 and SH-SY5Y cells. The binding affinity of (+)-NCFHEB (K(i): 0.064 nM) and (-)-NCFHEB (K(i): 0.112 nM) to human alpha4beta2 nAChR is in the same order of magnitude as that of epibatidine (K(i): 0.014 nM). However, because the affinity of both NCFHEB-enantiomers to human alpha3beta4 nAChR is up to 65 times lower than that of epibatidine, the alpha4beta2 subtype-specificity of NCFHEB is increased up to 1,400% compared to epibatidine.
Deuther-Conrad
Winnie
W
Institute of Interdisciplinary Isotope Research, Permoserstrasse 15, D-04318, Leipzig, Germany. conrad@iif-leipzig.de
Patt
Jörg Thomas
JT
Feuerbach
Dominik
D
Wegner
Florian
F
Brust
Peter
P
Steinbach
Jörg
J
D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000378:metabolism*; D002460:Cell Line; D006801:Humans; D018722:Nicotinic Agonists / Q000378:metabolism*; D011725:Pyridines / Q000378:metabolism*; D051381:Rats; D011978:Receptors, Nicotinic / Q000378:metabolism*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013788:Thalamus / Q000378:metabolism
D019086:Bridged Bicyclo Compounds, Heterocyclic; D018722:Nicotinic Agonists; D011725:Pyridines; D011978:Receptors, Nicotinic; C099184:norchloroepibatidine; C082748:epibatidine