Development of a new type of allosteric modulator of muscarinic receptors: hybrids of the antagonist AF-DX 384 and the hexamethonio derivative W84

Marion Mohr; Eberhard Heller; Ameneh Ataie; Klaus Mohr; Ulrike Holzgrabe

doi:10.1021/jm031095t

Development of a new type of allosteric modulator of muscarinic receptors: hybrids of the antagonist AF-DX 384 and the hexamethonio derivative W84

J Med Chem. 2004 Jun 3;47(12):3324-7. doi: 10.1021/jm031095t.

Authors

Marion Mohr¹, Eberhard Heller, Ameneh Ataie, Klaus Mohr, Ulrike Holzgrabe

Affiliation

¹ Institute of Pharmacy and Food Chemistry, Pharmaceutical Chemistry, University of Würzburg, Am Hubland, 97074 Würzburg, Germany.

PMID: 15163212
DOI: 10.1021/jm031095t

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Allosteric Regulation
Animals
Guinea Pigs
In Vitro Techniques
Isoindoles
Muscarinic Antagonists / chemical synthesis*
Muscarinic Antagonists / chemistry
Muscarinic Antagonists / pharmacology
Myocardium / metabolism
Phthalimides / chemical synthesis*
Phthalimides / chemistry
Phthalimides / pharmacology
Pirenzepine / analogs & derivatives*
Pirenzepine / chemical synthesis*
Pirenzepine / chemistry
Pirenzepine / pharmacology
Radioligand Assay
Receptors, Muscarinic / metabolism
Stereoisomerism
Structure-Activity Relationship
Swine

Substances

Isoindoles
Muscarinic Antagonists
Phthalimides
Receptors, Muscarinic
AFDX 384
hexamethylenebis(dimethyl-(3-phthalimidopropyl)ammonium bromide)
Pirenzepine