The possible role of group II metabotropic glutamate receptors for the treatment of schizophrenia

Abstract

Glutamate dysregulation is hypothesized to be involved in the pathophysiology of schizophrenia. It was suggested that NMDA hypofunction plays a major role in this complex disorder. The metabotropic glutamate receptors are distributed in the brain regions related to schizophrenia and seem to affect glutamate release in a moderate way. Compounds modulating these receptors are being investigated in animal models of schizophrenia, in an attempt to discover new antipsychotics. Most of the studies in recent years focused on the role of Group I and II metabotropic receptors in the drug treatment of schizophrenia. Group II agonists have shown beneficial effects in animal models of schizophrenia as well as in humans. It seems that metabotropic glutamate receptor (mGluRs) modulators could be developed into a novel treatment of schizophrenia by altering glutamate release, thus overcoming the putative impaired glutamate release. Although the implications from these pre-clinical studies to human schizophrenia patients are premature, the data obtained with some mGluRs modulators point to promising results for drug development. More studies, with compounds active at other mGluRs in animal models and schizophrenia patients, are needed to clarify the role of the mGluRs, especially in mGluRsII in the neurobiology and pharmacology of schizophrenia.