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Elevation of Ligand Binding to Muscarinic M2 Acetylcholine Receptors by Bis(ammonio)alkane-Type Allosteric Modulators

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journal contribution
posted on 11.07.2002, 00:00 authored by Alexandra Raasch, Olaf Scharfenstein, Christian Tränkle, Ulrike Holzgrabe, Klaus Mohr
Bis(ammonio)alkane-type compounds are archetypal muscarinic allosteric modulators. Phthalimido-substituted hexane-bis-ammonium agents were methylated in the phthalimide moieties and the lateral propyl side chains. All compounds retarded allosterically the dissociation of the orthosteric ligand [3H]N-methylscopolamine ([3H]NMS) from porcine heart M2 receptors. [3H]NMS equilibrium binding was reduced, left unaltered, or elevated, depending on the degree and position of methylation. This is the first time that an allosteric elevation of ligand binding is demonstrated for bis(ammonio)alkane-type compounds.