Novel inhibitors of the type 1 transporter for glycine (GlyT1) as antipsychotic agents

Abstract

The glutamatergic hypothesis of schizophrenia states that the positive, negative and cognitive symptoms of this devastating disease originate with a deficit in transmission at the NMDA class of glutamate receptors. By regulating levels of the NMDA co-agonist glycine, the type 1 transporter for glycine (GlyT1) may play a role in restoring normal levels of NMDA function in schizophrenic patients. This article extends an earlier review in this journal by reviewing recent advances in this field, and focuses on a recent series of GlyT1 inhibitors disclosed by Sanofi. In particular, the extensive characterisation reported for their lead compound, SSR-504734, reveals a promising profile for a novel antipsychotic agent.

Keywords::

• antipsychotic
• glycine transporter
• NMDA receptor
• SSR-504734