High affinity ligands for the alpha7 nicotinic receptor that show no cross-reactivity with the 5-HT3 receptor.
Potent and selective ligands of the alpha7 nicotinic acetylcholine receptor are required to understand the pharmacological effect of alpha7 activation. A common cross-reactivity occurs with serotonergic 5-HT3 receptors with which alpha7 receptors have a high sequence homology. We demonstrate that certain quinuclidine 3-biaryl carboxamides are high affinity alpha7 ligands with an excellent binding selectivity over 5-HT3 receptors.
Baker
S Richard
SR
Eli Lilly and Company Ltd., Lilly Research Centre, Erl Wood Manor, Windlesham, Surrey, GU20 6PH, UK.
Boot
John
J
Brunavs
Michael
M
Dobson
David
D
Green
Rachel
R
Hayhurst
Lorna
L
Keenan
Martine
M
Wallace
Louise
L
D000577:Amides / Q000138:chemical synthesis* / Q000737:chemistry; D003429:Cross Reactions; D016503:Drug Delivery Systems; D006801:Humans; D008024:Ligands; D011485:Protein Binding; D011812:Quinuclidines / Q000138:chemical synthesis* / Q000737:chemistry; D011869:Radioligand Assay; D011978:Receptors, Nicotinic / Q000737:chemistry*; D044406:Receptors, Serotonin, 5-HT3 / Q000737:chemistry*; D013329:Structure-Activity Relationship; D064569:alpha7 Nicotinic Acetylcholine Receptor
D000577:Amides; C579167:Chrna7 protein, human; D008024:Ligands; D011812:Quinuclidines; D011978:Receptors, Nicotinic; D044406:Receptors, Serotonin, 5-HT3; D064569:alpha7 Nicotinic Acetylcholine Receptor