Recent patents on positive allosteric modulators of the metabotropic glutamate 5 receptor as a potential treatment for schizophrenia.
The glutamate hypothesis of schizophrenia suggests that hypofunction of N-methyl-D-aspartate (NMDA) receptors may be critical for schizophrenic symptoms; therefore, pharmacological approaches that enhance NMDA function may be beneficial for the treatment of schizophrenia. Several lines of evidence indicate that NMDA and metabotropic glutamate (mGlu) 5 receptors are closely associated signaling partners and that a selective mGlu5 receptor agonist might provide a viable approach for increasing NMDA receptor function in the treatment of schizophrenia. The orthosteric binding sites across members of the mGlu receptor subtype for a particular endogenous ligand are often highly conserved, making it difficult to achieve high selectivity for the specific mGlu5 receptor. The advanced currents of drug discovery have developed multiple highly selective allosteric modulators of mGlu5 receptors. In the present review, we provide an update of the recent patents and development of positive allosteric modulators of the mGlu5 receptor and explore their therapeutic potential for schizophrenia.
Kanuma
Kosuke
K
Medicinal Chemistry Laboratories, Molecular Function and Pharmacology Laboratories, Taisho Pharmaceutical Co., Ltd., 1-403 Yoshino-cho, Kita-ku, Saitama, Saitama 331-9530, Japan. k.kanuma@po.rd.taisho.co.jp
Aoki
Takeshi
T
Shimazaki
Youichi
Y
D000494:Allosteric Regulation / Q000187:drug effects; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology / Q000627:therapeutic use*; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D010330:Patents as Topic; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists / Q000737:chemistry* / Q000378:metabolism*; D012559:Schizophrenia / Q000188:drug therapy* / Q000378:metabolism
D014150:Antipsychotic Agents; D018690:Excitatory Amino Acid Agonists; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; D018698:Glutamic Acid