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Metabotropic Glutamate Receptor Subtype 5 Positron-Emission-Tomography Radioligands as a Tool for Central Nervous System Drug Development: Between Progress and Setbacks

The metabotropic glutamate receptor subtype 5 (mGluR5) is a class C G-protein-coupled receptor (GPCR) that has been implicated in various neuronal processes and, consequently, in several neuropsychiatric or neurodevelopmental disorders. Over the past few decades, mGluR5 has become a major focus for...

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Autores principales: Dupont, Anne-Claire, Arlicot, Nicolas, Vercouillie, Johnny, Serrière, Sophie, Maia, Serge, Bonnet-Brilhault, Frédérique, Santiago-Ribeiro, Maria-Joao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10458693/
https://www.ncbi.nlm.nih.gov/pubmed/37631042
http://dx.doi.org/10.3390/ph16081127
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author Dupont, Anne-Claire
Arlicot, Nicolas
Vercouillie, Johnny
Serrière, Sophie
Maia, Serge
Bonnet-Brilhault, Frédérique
Santiago-Ribeiro, Maria-Joao
author_facet Dupont, Anne-Claire
Arlicot, Nicolas
Vercouillie, Johnny
Serrière, Sophie
Maia, Serge
Bonnet-Brilhault, Frédérique
Santiago-Ribeiro, Maria-Joao
author_sort Dupont, Anne-Claire
collection PubMed
description The metabotropic glutamate receptor subtype 5 (mGluR5) is a class C G-protein-coupled receptor (GPCR) that has been implicated in various neuronal processes and, consequently, in several neuropsychiatric or neurodevelopmental disorders. Over the past few decades, mGluR5 has become a major focus for pharmaceutical companies, as an attractive target for drug development, particularly through the therapeutic potential of its modulators. In particular, allosteric binding sites have been targeted for better specificity and efficacy. In this context, Positron Emission Tomography (PET) appears as a useful tool for making decisions along a drug candidate’s development process, saving time and money. Thus, PET provides quantitative information about a potential drug candidate and its target at the molecular level. However, in this area, particular attention has to be given to the interpretation of the PET signal and its conclusions. Indeed, the complex pharmacology of both mGluR5 and radioligands, allosterism, the influence of endogenous glutamate and the choice of pharmacokinetic model are all factors that may influence the PET signal. This review focuses on mGluR5 PET radioligands used at several stages of central nervous system drug development, highlighting advances and setbacks related to the complex pharmacology of these radiotracers.
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spelling pubmed-104586932023-08-27 Metabotropic Glutamate Receptor Subtype 5 Positron-Emission-Tomography Radioligands as a Tool for Central Nervous System Drug Development: Between Progress and Setbacks Dupont, Anne-Claire Arlicot, Nicolas Vercouillie, Johnny Serrière, Sophie Maia, Serge Bonnet-Brilhault, Frédérique Santiago-Ribeiro, Maria-Joao Pharmaceuticals (Basel) Review The metabotropic glutamate receptor subtype 5 (mGluR5) is a class C G-protein-coupled receptor (GPCR) that has been implicated in various neuronal processes and, consequently, in several neuropsychiatric or neurodevelopmental disorders. Over the past few decades, mGluR5 has become a major focus for pharmaceutical companies, as an attractive target for drug development, particularly through the therapeutic potential of its modulators. In particular, allosteric binding sites have been targeted for better specificity and efficacy. In this context, Positron Emission Tomography (PET) appears as a useful tool for making decisions along a drug candidate’s development process, saving time and money. Thus, PET provides quantitative information about a potential drug candidate and its target at the molecular level. However, in this area, particular attention has to be given to the interpretation of the PET signal and its conclusions. Indeed, the complex pharmacology of both mGluR5 and radioligands, allosterism, the influence of endogenous glutamate and the choice of pharmacokinetic model are all factors that may influence the PET signal. This review focuses on mGluR5 PET radioligands used at several stages of central nervous system drug development, highlighting advances and setbacks related to the complex pharmacology of these radiotracers. MDPI 2023-08-10 /pmc/articles/PMC10458693/ /pubmed/37631042 http://dx.doi.org/10.3390/ph16081127 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Dupont, Anne-Claire
Arlicot, Nicolas
Vercouillie, Johnny
Serrière, Sophie
Maia, Serge
Bonnet-Brilhault, Frédérique
Santiago-Ribeiro, Maria-Joao
Metabotropic Glutamate Receptor Subtype 5 Positron-Emission-Tomography Radioligands as a Tool for Central Nervous System Drug Development: Between Progress and Setbacks
title Metabotropic Glutamate Receptor Subtype 5 Positron-Emission-Tomography Radioligands as a Tool for Central Nervous System Drug Development: Between Progress and Setbacks
title_full Metabotropic Glutamate Receptor Subtype 5 Positron-Emission-Tomography Radioligands as a Tool for Central Nervous System Drug Development: Between Progress and Setbacks
title_fullStr Metabotropic Glutamate Receptor Subtype 5 Positron-Emission-Tomography Radioligands as a Tool for Central Nervous System Drug Development: Between Progress and Setbacks
title_full_unstemmed Metabotropic Glutamate Receptor Subtype 5 Positron-Emission-Tomography Radioligands as a Tool for Central Nervous System Drug Development: Between Progress and Setbacks
title_short Metabotropic Glutamate Receptor Subtype 5 Positron-Emission-Tomography Radioligands as a Tool for Central Nervous System Drug Development: Between Progress and Setbacks
title_sort metabotropic glutamate receptor subtype 5 positron-emission-tomography radioligands as a tool for central nervous system drug development: between progress and setbacks
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10458693/
https://www.ncbi.nlm.nih.gov/pubmed/37631042
http://dx.doi.org/10.3390/ph16081127
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