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Updated: Sep 2, 2026

Subcutaneous Administration of Muscarinic Antagonists and Triple-Immunostaining of the Levator Auris Longus Muscle in Mice
Published on: September 8, 2011
Development of covalent agonists for the muscarinic acetylcholine receptor
Katrin Eitel1, Philipp Risel1, Jonas Kaindl1
1Department of Chemistry and Pharmacy, Medicinal Chemistry, Friedrich-Alexander-Universität Erlangen-Nürnberg, Nikolaus-Fiebiger-Str. 10, 91058 Erlangen, Germany; FAU NeW - Research Center New Bioactive Compounds, Friedrich-Alexander-Universität Erlangen-Nürnberg, Nikolaus-Fiebiger-Str. 10, 91058 Erlangen, Germany.
Abstract:
Binding affinity and residence time of endogenous and synthetic receptor ligands are often poor at the tissue to be treated. Covalent ligands targeting G protein-coupled receptors (GPCRs) have gained significant interest because they unite the high specificity and selectivity with the prolonged activity resulting from irreversible or slowly reversible binding. Using the muscarinic acetylcholine receptor (mAChR) agonists iperoxo (5), PR15 (7), and carbachol (9) as lead compounds, we developed the covalent muscarinic receptor agonists 8 and 10 functionalized by a mustard-type reactive group. Radioligand depletion and functional properties clearly indicated covalent binding and activation of the therapeutically relevant muscarinic acetylcholine receptor.
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