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For example, partial agonists at the NMDAR glycine B binding site, such as GLYX-13 (rapastinel) and D-cycloserine, produced antidepressant effects in both human and animal studies ( Metabotropic Receptors Metabotropic glutamatergic receptors (mGluR)[homodimers], which are mainly distributed in corticolimbic areas, can be broadly divided into three categories according to their structures, ligand recognition profiles and coupling to cellular transduction systems: group I (mGluR1 and 5) receptors, group II (mGluR2 and 3), and group III (mGluR4, 6,7 and 8) ( Group I mGluR antagonists mimic certain properties of NMDA antagonists to some extent such as their influence on mood, as well as their neuroprotective effects ( While group I receptors are positively coupled with Phospholipase C via Gq, group II and III receptors, on the other hand, are positively coupled to Gi, leading to an inhibitory effect on adenylyl cyclase (Figure 1, mGluR 2/3 antagonists are thought to enhance synaptic glutamate levels, thereby boosting AMPAR transmission and firing rates and extracellular monoamine levels

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