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Competition radioligand binding assays for the investigation of bispyridinium compound affinities to the human muscarinic acetylcholine receptor subtype 5 (hM 5 )
Author(s) -
Niessen K. V.,
Tattersall J. E. H.,
Timperley C. M.,
Bird M.,
Green C.,
Thiermann H.,
Worek F.
Publication year - 2012
Publication title -
drug testing and analysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.065
H-Index - 54
eISSN - 1942-7611
pISSN - 1942-7603
DOI - 10.1002/dta.410
Subject(s) - muscarinic acetylcholine receptor , pharmacology , acetylcholine , chemistry , radioligand , atropine , acetylcholine receptor , muscarinic acetylcholine receptor m4 , muscarinic acetylcholine receptor m3 , muscarinic acetylcholine receptor m2 , muscarinic acetylcholine receptor m1 , receptor , nicotinic agonist , muscarinic acetylcholine receptor m5 , nerve agent , radioligand assay , biochemistry , biology , acetylcholinesterase , endocrinology , enzyme
Standard treatment of poisoning by organophosphorus (OP) nerve agents with atropine and oximes lacks efficacy with some nerve agents. Promising in vitro and in vivo results were obtained with the bispyridinium compound SAD‐128 which was partly attributed to its interaction with nicotinic acetylcholine receptors. Previous studies indicate that bispyridinium compounds interact with muscarinic acetylcholine receptors as well. The muscarinic M 5 receptor is not well investigated compared to other subtypes, but could be important in the search for new drugs for treating nerve agent poisoning. A set of bispyridinium compounds structurally related to SAD‐128 were tested in competition binding experiments with recombinant human M 5 muscarinic acetylcholine receptors. Five of the six investigated bispyridinium compounds interacted with the orthosteric binding site, with affinities in the low micromolar range. These data indicate that interaction of bispyridinium compounds with muscarinic receptors may contribute to their therapeutic efficacy. Copyright © 2012 John Wiley & Sons, Ltd.