Abstract
Antagonists to the human metabotropic glutamate receptor subtype 5a(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.
MeSH terms
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Calcium / analysis*
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Calcium / chemistry
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Calcium / metabolism
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Cell Line
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Dose-Response Relationship, Drug
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Excitatory Amino Acid Antagonists / analysis
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Excitatory Amino Acid Antagonists / pharmacology*
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Fluorescence
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Fluorescent Dyes / chemistry
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Fluorometry / instrumentation
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Fluorometry / methods*
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Glutamic Acid / chemistry
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Glutamic Acid / pharmacology
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Humans
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Intracellular Fluid / chemistry
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Intracellular Fluid / metabolism
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Kinetics
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Photomicrography
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Receptor, Metabotropic Glutamate 5
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Receptors, Metabotropic Glutamate / agonists
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Receptors, Metabotropic Glutamate / antagonists & inhibitors*
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Sensitivity and Specificity
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Transfection
Substances
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Excitatory Amino Acid Antagonists
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Fluorescent Dyes
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Receptor, Metabotropic Glutamate 5
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Receptors, Metabotropic Glutamate
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Glutamic Acid
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Calcium