Detailed In Vitro Pharmacological Characterization of Clinically Tested Negative Allosteric Modulators of the Metabotropic Glutamate Receptor 5.

ABSTRACT: Negative allosteric modulation of the metabotropic glutamate 5 (mGlu₅) receptor has emerged as a potential strategy for the treatment of neurologic disorders. Despite the success in preclinical studies, many mGlu₅ negative allosteric modulators (NAMs) that have reached clinical trials failed due to lack of efficacy. In this study, we provide a detailed in vitro pharmacological characterization of nine clinically and preclinically tested NAMs. We evaluated inhibition of l-glutamate-induced signaling with Ca²⁺ mobilization, inositol monophosphate (IP₁) accumulation, extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation, and real-time receptor internalization assays on rat mGlu₅ expressed in HEK293A cells. Moreover, we determ

SUBMITTER: Arsova A 

PROVIDER: S-EPMC7705108 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature