title: Neurobiological insights and novel therapeutic opportunities for CNS disorders from mGlu receptor allosteric and biased modulation.
abstract: The metabotropic glutamate (mGlu) receptor family is a potential therapeutic target for multiple central nervous system (CNS) disorders. However, aspects of mGlu receptor signaling and their role in neural pathways remain to be fully elucidated. Novel subtype selective allosteric modulators have revealed new roles for mGlu receptors in brain health and disease, as well as expanding on previously underappreciated aspects of mGlu signaling such as biased agonism and modulation. Recent advances have improved our understanding of mGlu receptor function. Harnessing these new insights to inform drug discovery programs has the potential to lead to the design and discovery of mGlu allosteric modulators that specifically drive glutamatergic activity toward therapeutically beneficial effects and avoid on-target adverse effect liability.
authors.affiliation: Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences and Department of Pharmacology, Monash University, Parkville, VIC, Australia.
authors.forename: Shane
authors.initials: S
authors.lastname: Hellyer
authors.affiliation: Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences and Department of Pharmacology, Monash University, Parkville, VIC, Australia.
authors.forename: Katie
authors.initials: K
authors.lastname: Leach
authors.affiliation: Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences and Department of Pharmacology, Monash University, Parkville, VIC, Australia. Electronic address: karen.gregory@monash.edu.
authors.forename: Karen J
authors.initials: KJ
authors.lastname: Gregory
mesh_terms: D000494:Allosteric Regulation / Q000187:drug effects; D000818:Animals; D002493:Central Nervous System Diseases / Q000188:drug therapy* / Q000503:physiopathology; D015195:Drug Design; D055808:Drug Discovery / Q000379:methods; D006801:Humans; D058990:Molecular Targeted Therapy; D018094:Receptors, Metabotropic Glutamate / Q000187:drug effects* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D018094:Receptors, Metabotropic Glutamate