The mGlu7 receptor in schizophrenia-An update and future perspectives

The mGlu7 receptor belongs to the III group of metabotropic glutamatergic (mGlu) receptors and physiologically serves as an emergency receptor that is activated by high, almost pathological, glutamate concentrations. Of all mGlu receptors, this receptor is most highly expressed in the brain. Additionally, relatively intense expression of the receptor was found at the periphery, for example in the bowels or in the reproductive system of male mice, but this review will be focused predominantly on its role in the brain. In the CNS, the receptor is expressed presynaptically, in the center of the synaptic cleft, at the terminals of both excitatory glutamatergic and inhibitory GABAergic neurons. Thus, it may regulate the release of both glutamate and GABA. Schizophrenia is thought to develop as a consequence of a disturbed glutamatergic-GABAergic balance in different parts of the brain. Thus, the mGlu7 receptor may be involved in the pathophysiology of schizophrenia and consequently constitute the target for antipsychotic drug discovery. In this review, we summarize the available data about mGlu7 receptor ligands and their activity in animal models of schizophrenia. At present, only a few ligands are available, and negative allosteric modulators (NAMs) appear to exert antipsychotic-like efficacy, indicating that the inhibition of the receptor could constitute a promising target in the search for novel drugs. Additionally, the data concerning the expression of the receptor in the CNS and putative mechanisms by which its inhibition may contribute to the treatment of schizophrenia will be discussed. Finally, the polymorphisms of genes encoding the receptor in schizophrenic patients will also be provided.

Automated summary

The mGlu7 receptor is highly expressed in the brain and may be involved in the pathophysiology of schizophrenia, serving as a potential target for antipsychotic drug discovery. Ligands of this receptor show promise in animal models of schizophrenia, particularly negative allosteric modulators (NAMs), suggesting that inhibiting the receptor could be a promising approach in developing novel treatments. The expression of the receptor in the CNS and potential mechanisms by which its inhibition may contribute to the treatment of schizophrenia, along with genetic polymorphisms in schizophrenic patients, are also discussed in this review.