mGlu2/3 and mGlu5 receptors: potential targets for novel antidepressants.
Major depressive disorder is among the most prevalent forms of mental illness. All currently available antidepressant medications have stemmed from study of the mechanisms of serendipitously discovered drugs, and only 30-50% of patients exhibit remission and frequently at least 3-4 weeks are required for manifestation of significant therapeutic effects. To overcome these drawbacks, discovering novel neuronal mechanisms of pathophysiology of depression as well as more effective treatments are necessary. This review focuses on the metabotropic glutamate (mGlu) receptors and their potential for drug targets for the treatment of depression. In particular, accumulating evidence has indicated the potential importance and usefulness of agents acting on mGlu2/3 and mGlu5 receptors. Preclinical and clinical evidence of mGlu2/3 receptor ligands and mGlu5 receptor antagonists are described. Moreover, their potential in clinic will be discussed in the context of neuronal mechanisms of ketamine, an agent recently demonstrated a robust effect for patients with treatment-resistant depression. This article is part of a Special Issue entitled 'Metabotropic Glutamate Receptors'.
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
Shigeyuki
S
Chaki
Yukio
Y
Ago
Agnieszka
A
Palucha-Paniewiera
Francesco
F
Matrisciano
Andrzej
A
Pilc
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D003865:Major Depressive Disorder / Q000188:drug therapy*; D018683:Excitatory Amino Acid Agents / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D007649:Ketamine / Q000627:therapeutic use; D008959:Models, Neurological; D058990:Molecular Targeted Therapy / Q000379:methods*; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists / Q000037:antagonists & inhibitors; D009435:Synaptic Transmission / Q000187:drug effects
D000928:Antidepressive Agents; D018683:Excitatory Amino Acid Agents; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; C108822:metabotropic glutamate receptor 2; C102718:metabotropic glutamate receptor 3; D007649:Ketamine