mGlu2/3 receptor agonist (LY354740) in anxiety

mGlu2/3 Receptors (LY354740) in Anxiety mGlu2/3 receptors when activated decrease glutamate excitation on limbic synapses involved in anxiety. The orally active agonist compound LY354740 (or prodrug LY544344) was active in animal and human models of stress/anxiety. Later clinical studies showed effi...

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Published in:Pharmacology, biochemistry and behavior biochemistry and behavior, 2024-09, Vol.242, p.173826, Article 173826
Main Author: Schoepp, Darryle D.
Format: Article
Language:English
Subjects:
Animals
Anti-Anxiety Agents - pharmacology
Anti-Anxiety Agents - therapeutic use
Anxiety
Anxiety - drug therapy
Bridged Bicyclo Compounds
Excitatory Amino Acid Agonists - pharmacology
Excitatory Amino Acid Agonists - therapeutic use
Glutamate receptors
Humans
Neuroscience
Pharmacology
Prodrugs - pharmacology
Receptors, Metabotropic Glutamate - agonists
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Summary:mGlu2/3 Receptors (LY354740) in Anxiety mGlu2/3 receptors when activated decrease glutamate excitation on limbic synapses involved in anxiety. The orally active agonist compound LY354740 (or prodrug LY544344) was active in animal and human models of stress/anxiety. Later clinical studies showed efficacy in generalized anxiety in patients, validating this mechanism clinically. However, the compound was terminated due to rodent seizures in long-term toxicology studies. •mGlu2/3 receptor agonists like LY354740 reduce limbic excitability.•mGlu2/3 receptor agonists like LY354740 are active in animal models of anxiety.•In clinical studies the mGlu2/3 receptor agonist LY354740 or its oral prodrug reduced anxiety in generalized anxiety patients.•LY354740 or its prodrug LY544344 did not have benzodiazepine like sides effects in humans.
ISSN:0091-3057
1873-5177
1873-5177
DOI:10.1016/j.pbb.2024.173826