Drugs to tune up glutamatergic systems: Modulators of glutamate metabotropic receptors

Kathy Sengmany, Karen J. Gregory

Research output: Chapter in Book/Report/Conference proceedingChapter (Book)Researchpeer-review

1 Citation (Scopus)


The metabotropic glutamate (mGlu) receptors are Class C G protein-coupled receptors that offer promising potential therapeutic targets for multiple central nervous system (CNS) disorders. Dysfunction or dysregulation of the glutamatergic system, the main excitatory neurotransmitter system in the CNS, is thought to be associated with multiple CNS disorders including schizophrenia, depression, anxiety, Fragile X syndrome, Parkinson’s disease, and refractory chronic pain. Here, we describe drug discovery and development approaches for targeting mGlu receptors, with particular focus on allosteric modulation and biased agonism. Binding to allosteric sites that are topographically distinct from the endogenous binding site, allows for increased selectivity between receptor subtypes, and maintaining tonal and temporal glutamatergic responses. Biased agonism allows for further specialization, with the potential to design drugs that target desired receptor responses at the exclusion of those leading to adverse effects. Collectively, these newer paradigms of drug action offer the promise for discovery of therapeutics with favorable outcomes and minimized adverse effects within the delicate CNS environment.

Original languageEnglish
Title of host publicationBiochemical Approaches for Glutamatergic Neurotransmission
EditorsSandrine Parrot, Luc Denoroy
Place of PublicationNew York NY USA
PublisherHumana Press
Number of pages35
ISBN (Electronic)9781493972289
ISBN (Print)9781493972272
Publication statusPublished - 1 Jan 2018

Publication series

ISSN (Print)0893-2336
ISSN (Electronic)1940-6045


  • Allosteric modulator
  • Biased agonism
  • Metabotropic glutamate receptor

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