Are compounds acting at metabotropic glutamate receptors the answer to treating depression?

Numerous studies over the last few years have suggested that modulating the glutamatergic system may be an efficient method to achieve an antidepressant effect. Data suggest that metabotropic glutamate receptors (mGlu receptors), related to long-term, modulatory effects on glutamatergic neurotransmission, may be a good target for the development of new, effective and safe therapeutic drugs to treat several CNS disorders including depression and anxiety. Several potent, selective and systemically active orthosteric and allosteric ligands of specific mGlu receptor subtypes have been discovered and these have been tested as potential antidepressants in models of depression in rodents. The mGluR5 antagonists and group II mGlu receptor antagonists seem to be the most promising compounds with potential antidepressant-like activity; however, the efficacy of mGlu receptor ligands in the clinical setting is still an unanswered question.