Identification of metabotropic glutamate receptor antagonists using an automated high-throughput screening system

Abstract Antagonists to the human metabotropic glutamate receptor subtype 5 a (mGluR 5a ) have been implicated as potential therapeutics for the treatment of a variety of nervous system disorders, including pain, anxiety, and Parkinson’s disease. To discover novel antagonists to the mGluR 5a , a functional assay measuring agonist-induced intracellular calcium release was developed. The assay was used for the high-throughput screening of a large collection of compounds in single wells using a fully automated robotic platform. Primary high-throughput screening hits were subjected to a combination of data analysis and counterscreening assays to identify several compounds with both efficacy and selectivity for the metabotropic glutamate receptor target.