Metabotropic glutamate receptors as targets for novel anxiolytics

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HighlightsPositive correlation between mGlu5 receptor signaling and anxiety-related symptoms.mGlu5 receptor NAMs reduce OCD-like symptoms in preclinical studies.Activation of mGlu4 receptors abolishes chronic pain-induced anxiety in mice.Therapeutic potential of mGlu receptor modulation for anxiety disorders.Anxiety disorders are highly prevalent psychiatric illnesses posing an important social and economic burden. Their current pharmacotherapy shows short term efficacy, though nearly one third of patients do not achieve sustained remission. There is, therefore, a strong medical need for new therapeutic agents acting through novel mechanisms of action. Considerable work has focused on metabotropic glutamate (mGlu) receptors as potential targets for novel anxiolytics. Ligands acting at mGlu receptors showed promising results in preclinical studies, whereas their efficacy was dubious in clinical trials. Recent preclinical and clinical studies have opened new prospects for targeting mGlu receptors to treat anxiety disorders. This review provides an outlook on these progresses.

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