Metabotropic glutamate receptors in the tripartite synapse as a target for new psychotropic drugs

Abstract

Mental disorders, such as depression, anxiety and schizophrenia, has become a large medical and social problem recently. Studies performed in animal tests and early clinical investigations brought a new insight in the pharmacotherapy of these disorders. Latest investigations are focused mainly on the glutamatergic system, a main excitatory amino acid neurotransmitter in the brain. Evidence indicates that metabotropic glutamate receptors ligands have excellent antidepressant, anxiolytic and antipsychotic effects. Metabotopic glutamate receptors (mGlu) divaded into three groups (group I, II and III) are localized on nerve terminals, postsynaptic sites and glial cells and thus they can influence and modulate the action of glutamate on different levels in the synapse. Recent advances in the identification of selective and specific compounds (both ortho- and allosteric ligands), and the generation of transgenic animals enabled to have new insight into the pathophysiology and therapy of mood disorders. At present, the most potent seem to be negative allosteric modulators of the first group (mGlu1 and mGlu5), and positive allosteric modulators of the second (mGlu2 and mGlu3) and third (mGlu4/7/8) group of mGlu receptors.