Elevation of ligand binding to muscarinic M(2) acetylcholine receptors by bis(ammonio)alkane-type allosteric modulators.
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 [(3)H]N-methylscopolamine ([(3)H]NMS) from porcine heart M(2) receptors. [(3)H]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.
Raasch
Alexandra
A
Pharmacology and Toxicology, Institute of Pharmacy, University of Bonn, An der Immenburg 4, 53121 Bonn, Germany.
Scharfenstein
Olaf
O
Tränkle
Christian
C
Holzgrabe
Ulrike
U
Mohr
Klaus
K
D000494:Allosteric Regulation; D000818:Animals; D066298:In Vitro Techniques; D008024:Ligands; D009206:Myocardium / Q000378:metabolism; D000644:Quaternary Ammonium Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011869:Radioligand Assay; D043585:Receptor, Muscarinic M2; D011976:Receptors, Muscarinic / Q000378:metabolism*; D013552:Swine
D008024:Ligands; D000644:Quaternary Ammonium Compounds; D043585:Receptor, Muscarinic M2; D011976:Receptors, Muscarinic