Metabotropic glutamate receptors as novel targets for anxiety and stress disorders

Swanson, Chad J.; Bures, Mark; Johnson, Michael P.; Linden, Anni-Maija; Monn, James A.; Schoepp, Darryle D.

doi:10.1038/nrd1630

Cited by 607Neuroscience and Neuropharmacology ResearchNeurotransmitter Receptor Influence on BehaviorTreatment of Major Depression

Metabotropic glutamate receptors as novel targets for anxiety and stress disorders

Swanson, Chad J., Bures, Mark, Johnson, Michael P., Linden, Anni-Maija, Monn, James A., Schoepp, Darryle D.·2005·Nature Reviews Drug Discovery

DOI 10.1038/nrd1630

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Abstract

Anxiety and stress disorders are the most commonly occurring of all mental illnesses, and current treatments are less than satisfactory. So, the discovery of novel approaches to treat anxiety disorders remains an important area of neuroscience research. Glutamate is the major excitatory neurotransmitter in the mammalian central nervous system, and G-protein-coupled metabotropic glutamate (mGlu) receptors function to regulate excitability via pre- and postsynaptic mechanisms. Various mGlu receptor subtypes, including group I (mGlu(1) and mGlu(5)), group II (mGlu(2) and mGlu(3)), and group III (mGlu(4), mGlu(7) and mGlu(8)) receptors, specifically modulate excitability within crucial brain structures involved in anxiety states. In addition, agonists for group II (mGlu(2/3)) receptors and antagonists for group I (in particular mGlu(5)) receptors have shown activity in animal and/or human conditions of fear, anxiety or stress. These studies indicate that metabotropic glutamate receptors are interesting new targets to treat anxiety disorders in humans.

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Studies in rodents suggest that GRM8 and GRM7 have broadly opposite effects on anxiety levels, with GRM8 activation tending to be closer to Group II metabotropic receptors in its anxiolytic effects, while GRM7 seems to be more anxiety- and aggression-inducing.
“Studies in rodents suggest that GRM8 and GRM7 have broadly opposite effects on anxiety levels, with GRM8 activation tending to be closer to Group II metabotropic receptors in its anxiolytic effects, while GRM7 seems to be more anxiety-(and aggression-)inducing (Swanson et al., 2005).”
From Glutamate receptors in domestication and modern human evolution (2020) · cites this paper as Swanson et al., 2005

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Authors: Swanson, C. J., Bures, M., Johnson, M. P., Linden, A.-M., Monn, J. A., & Schoepp, D. D.
Affiliations: Eli Lilly (United States) (US)
Corresponding author: Schoepp, Darryle D.
ORCID: Johnson, Michael P.
Linden, Anni-Maija
Venue: Nature Reviews Drug Discovery
Publisher: Springer Science and Business Media LLC
Published: 2005-01-24
Volume: 4
Issue: 2
Pages: 131-144
ISSN: 1474-1776 (ISSN-L)
1474-1784
DOI: 10.1038/nrd1630
OpenAlex: W2001311316
Cited by: 607
References: 131
Citations by year: 2026: 7 · 2025: 13 · 2024: 8 · 2023: 13 · 2022: 17 · 2021: 21 · 2020: 20 · 2019: 24 · 2018: 21 · 2017: 28 · 2016: 30 · 2015: 36 · 2014: 34 · 2013: 38 · 2012: 44
FWCI: 4.23
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Nature Reviews Drug Discovery (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
Keywords: metabotropic glutamate receptors, anxiety disorders, stress disorders, mGlu5 receptor antagonists, mGlu2/3 receptor agonists, group I metabotropic glutamate receptors, group II mGlu receptors, fear, therapeutic target
MeSH terms: Animals, Anxiety, Humans, Receptors, Metabotropic Glutamate, Stress Disorders, Traumatic

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Metabotropic glutamate receptors as novel targets for anxiety and stress disorders

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