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 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.