title: Development of a new type of allosteric modulator of muscarinic receptors: hybrids of the antagonist AF-DX 384 and the hexamethonio derivative W84.
abstract: 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 of W84 gave an allosteric enhancer of NMS binding. Thus, a new lead structure for the development of allosteric enhancers of NMS binding has been discovered.
authors.affiliation: Institute of Pharmacy and Food Chemistry, Pharmaceutical Chemistry, University of Würzburg, Am Hubland, 97074 Würzburg, Germany.
authors.forename: Marion
authors.initials: M
authors.lastname: Mohr
authors.forename: Eberhard
authors.initials: E
authors.lastname: Heller
authors.forename: Ameneh
authors.initials: A
authors.lastname: Ataie
authors.forename: Klaus
authors.initials: K
authors.lastname: Mohr
authors.forename: Ulrike
authors.initials: U
authors.lastname: Holzgrabe
mesh_terms: D000494:Allosteric Regulation; D000818:Animals; D006168:Guinea Pigs; D066298:In Vitro Techniques; D054833:Isoindoles; D018727:Muscarinic Antagonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D009206:Myocardium / Q000378:metabolism; D010797:Phthalimides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D010890:Pirenzepine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011869:Radioligand Assay; D011976:Receptors, Muscarinic / Q000378:metabolism; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013552:Swine
chemical_list: D054833:Isoindoles; D018727:Muscarinic Antagonists; D010797:Phthalimides; D011976:Receptors, Muscarinic; C065959:AFDX 384; C013017:hexamethylenebis(dimethyl-(3-phthalimidopropyl)ammonium bromide); D010890:Pirenzepine