title: Targeting of metabotropic glutamate receptors for the treatment of schizophrenia.
abstract: The glutamatergic system is involved in a wide range of physiological processes in the brain, and its dysfunction plays an important role in the etiology and pathophysiology of psychiatric disorders, including schizophrenia. Among the glutamate receptors, metabotropic receptors (mGlu receptors) have emerged as attractive therapeutic targets for the development of novel interventions for psychiatric disorders. Among them, group II mGlu receptors, such as mGlu2 and mGlu3 receptors, are of particular interest because of their unique distribution and the regulatory roles they have in neurotransmission. Recently, potent agonists for mGlu2/3 receptor have been synthesized, and their pharmacological roles have been intensively investigated in animal models. The efficacy for the treatment of schizophrenia has also been proven in a clinical trial. Recently, much attention has been paid to mGlu2 receptor potentiators, which potentiate the glutamate response without affecting the actual activity of the mGlu2 receptor. In addition, mGlu1 receptor antagonists have recently been proposed as an attractive approach to developing novel antipsychotics in animal models. This review describes the potential of both mGlu2/3 receptor agonists/potentiators and mGlu1 receptor antagonists for the treatment of schizophrenia.
authors.affiliation: Discovery Pharmacology, Molecular Function and Pharmacology Laboratories, Taisho Pharmaceutical Co., Ltd., 1-403 Yoshino-cho, Kita-ku, Saitama, Saitama 331-9530, Japan. s.chaki@po.rd.taisho.co.jp
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Chaki
authors.forename: Hirohiko
authors.initials: H
authors.lastname: Hikichi
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001921:Brain / Q000187:drug effects / Q000503:physiopathology*; D018698:Glutamic Acid / Q000502:physiology*; D006801:Humans; D051379:Mice; D058990:Molecular Targeted Therapy; D051381:Rats; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists* / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012559:Schizophrenia / Q000188:drug therapy* / Q000503:physiopathology*; D009435:Synaptic Transmission / Q000187:drug effects
chemical_list: D014150:Antipsychotic Agents; D018094:Receptors, Metabotropic Glutamate; C108822:metabotropic glutamate receptor 2; C102718:metabotropic glutamate receptor 3; C104077:metabotropic glutamate receptor type 1; D018698:Glutamic Acid