mGluRs & anxiety

mGluR5 inhibition (ADX10059)
Inhibition of mGluR5 is a clinically validated strategy for anxiety. Although it never made it to the market, fenobam, an mGluR5 antagonist, showed efficacy in Phase II testing of human generalized anxiety disorder. It was discontinued for reasons believed to be unrelated to its intended mechanism. A large number of preclinical models of anxiety have shown involvment of mGluR5. For example, a well characterized mGluR5 negative allosteric modulator (NAM), called MPEP, has been shown to have efficacy in various animal models of anxiety. MPEP is a "tool" compound that is not likely to be developed for use in humans. mGluR5 is found in brain regions implicated in anxiety.

mGluR2 activiation (ADX71149)
Activation of mGluR2 is a clinically validated strategy for anxiety. Development of a mGluR2/3 agonist from Eli Lilly & Co., which was shown to have efficacy in Phase II trial for anxiety, was discontinued because of issues believed to be unrelated to the product's intended mechanism. Activation of mGluR2 has been shown to be efficacious in multiple preclinical models of anxiety.

ADX10059 in anxiety
ADX71149 in anxiety
anxiety