Abstract
Multiple lines of evidence suggest that hypofunction of glutamatergic neurotransmission via N-methyl-Daspartate (NMDA) receptors might be implicated in the pathophysiology of schizophrenia. The NMDA receptor hypofunction hypothesis of schizophrenia suggests that increasing NMDA receptor function via pharmacological manipulation could provide a potential new strategy for the management of schizophrenia. Currently, the glycine modulatory sites on NMDA receptors present the most attractive therapeutic targets for the treatment of schizophrenia. One means of enhancing NMDA receptor neurotransmission is to increase the availability of the obligatory co-agonist glycine at modulatory sites through the inhibition of glycine transporter-1 (GlyT-1) on glial cells. With the aim of treating schizophrenia, a number of pharmaceutical industries have developed novel and selective GlyT-1 inhibitors, and recent studies have demonstrated that the GlyT-1 inhibitor sarcosine (N-methyl glycine) could be a potential drug. The present review considers GlyT-1 inhibitors as novel drugs for the treatment of schizophrenia.
Keywords: Schizophrenia, NMDA receptor, glutamate, glycine, transporter, glia
Central Nervous System Agents in Medicinal Chemistry
Title: Glycine Transporter-1 Inhibitors as Novel Therapeutic Drugs for Schizophrenia
Volume: 7 Issue: 3
Author(s): Kenji Hashimoto
Affiliation:
Keywords: Schizophrenia, NMDA receptor, glutamate, glycine, transporter, glia
Abstract: Multiple lines of evidence suggest that hypofunction of glutamatergic neurotransmission via N-methyl-Daspartate (NMDA) receptors might be implicated in the pathophysiology of schizophrenia. The NMDA receptor hypofunction hypothesis of schizophrenia suggests that increasing NMDA receptor function via pharmacological manipulation could provide a potential new strategy for the management of schizophrenia. Currently, the glycine modulatory sites on NMDA receptors present the most attractive therapeutic targets for the treatment of schizophrenia. One means of enhancing NMDA receptor neurotransmission is to increase the availability of the obligatory co-agonist glycine at modulatory sites through the inhibition of glycine transporter-1 (GlyT-1) on glial cells. With the aim of treating schizophrenia, a number of pharmaceutical industries have developed novel and selective GlyT-1 inhibitors, and recent studies have demonstrated that the GlyT-1 inhibitor sarcosine (N-methyl glycine) could be a potential drug. The present review considers GlyT-1 inhibitors as novel drugs for the treatment of schizophrenia.
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Cite this article as:
Hashimoto Kenji, Glycine Transporter-1 Inhibitors as Novel Therapeutic Drugs for Schizophrenia, Central Nervous System Agents in Medicinal Chemistry 2007; 7 (3) . https://dx.doi.org/10.2174/187152407781669161
DOI https://dx.doi.org/10.2174/187152407781669161 |
Print ISSN 1871-5249 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6166 |
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