Identification of a Novel Allosteric Site at the M₅ Muscarinic Acetylcholine Receptor.

ABSTRACT: The M₅ muscarinic acetylcholine receptor (mAChR) has emerged as an exciting therapeutic target for the treatment of addiction and behavioral disorders. This has been in part due to promising preclinical studies with the M₅ mAChR selective negative allosteric modulator (NAM), ML375. The binding site of ML375 remains unknown, however, making it difficult to develop improved M₅ mAChR selective modulators. To determine the possible location of the ML375 binding site, we used radioligand binding and functional assays to show that ML375 does not interact with the well-characterized "common" mAChR allosteric site located in the receptor's extracellular vestibule, nor a previously proposed second allosteric site recognized by the modulator, amiodarone. Molecular do

SUBMITTER: Burger WAC 

PROVIDER: S-EPMC7616173 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature