Recent Patents on CNS Drug Discovery

Vincenzo Di Marzo
Istituto di Chimica Biomolecolare (I.C.B.)
Consiglio Nazionale delle Ricerche (C.N.R.)
Via Campi Flegrei 34
Pozzuoli, Napoli 80078


Recent Patents on Positive Allosteric Modulators of the Metabotropic Glutamate 5 Receptor as a Potential Treatment for Schizophrenia

Author(s): Kosuke Kanuma, Takeshi Aoki and Youichi Shimazaki

Affiliation: Medicinal Chemistry Laboratories, Taisho Pharmaceutical Co., Ltd., 1-403 Yoshino-cho, Kita-ku, Saitama, Saitama 331-9530, Japan.


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 receptor. 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.

Keywords: Metabotropic glutamate (mGlu) 5 receptor, G-protein-coupled receptor (GPCR), positive allosteric modulator, potentiator, schizophrenia

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Article Details

Page: [23 - 34]
Pages: 12
DOI: 10.2174/157488910789753512