The structurally divergent agents gallamine and hexamethylene-bis-[dimethyl-(3-phthalimidopropyl)ammonium]dibromide (W84) are known to interact competitively at a common allosteric site on muscarinic receptors. Previous studies reported that the M2 selectivity of gallamine depended largely on the EDGE (172-175) sequence in the second
Journal of medicinal chemistry, 47(12), 3324-3327 (2004-05-28)
Various fragments of the hexamethonio-type allosteric agent W84 were linked to the secondary amino group of the muscarinic M(2) acetylcholine receptor-preferring antagonist AF-DX 384 to increase the area of attachment with the allosteric site. Addition of only the phthalimido moiety
Journal of molecular neuroscience : MN, 30(1-2), 165-168 (2006-12-29)
Allosteric modulators of ligand-receptor interactions are found for a variety of receptors (Christopoulos, 2002). Allosteric agents attach to a binding site being topographically distinct from the site for conventional (orthosteric) agonists or antagonists. In the case of the muscarinic receptor
The bis-quaternary W84, hexamethylene-bis-[dimethyl-(3-phthalimidopropyl)-ammonium bromide], is a potent allosteric modulator of M2-cholinoceptors. In this study we aimed at quantifying its allosteric effect on the dissociation of [3H]pirenzepine from M1-cholinoceptors in rat cerebral cortex and to measure the effects on association
The hypothesis was tested that M2-selective antagonists partially utilize the allosteric site of muscarinic M2 receptors. The interactions of the allosteric agent W84 (hexane-1, 6-bis[dimethyl-3'-phthalimidopropyl-ammonium bromide]) were studied with the M2/M4-selective AF-DX 384 [(+/-)-5, 11-dihydro-11-([(2-(2-[(dipropylamino)methyl]-1-piperidinyl)ethyl)amino]carbonyl)-6H-pyrido(2,3-b)(1,4)-benzodiazepine-6-one], the nonselective N-methylscopolamine (NMS), and
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