Glycine transporter-1 inhibitors as novel therapeutic drugs for schizophrenia
Glycine transporter-1 inhibitors as novel therapeutic drugs for schizophrenia
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DOI：
10.2174/187152407781669161
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发表时间：
2007-09-01
影响因子：
--
通讯作者：
Hashimoto, Kenji
中科院分区：
文献类型：
--
作者：
Hashimoto, Kenji
多种证据表明，通过N-甲基-D-天冬氨酸（NMDA）受体的多巴胺能神经传递功能减退可能与精神分裂症的病理生理有关。精神分裂症的NMDA受体功能低下假说表明，通过药物操作增加NMDA受体功能可能为精神分裂症的治疗提供一种潜在的新策略。目前，NMDA受体上的甘氨酸调节位点是治疗精神分裂症最有吸引力的治疗靶点。增强NMDA受体神经传递的一种方法是通过抑制神经胶质细胞上的甘氨酸转运蛋白-1（GlyT-1）来增加调节位点处的强制性共激动剂甘氨酸的可用性。为了治疗精神分裂症，许多制药行业已经开发出新型和选择性的GlyT-1抑制剂，最近的研究表明，GlyT-1抑制剂肌氨酸（N-甲基甘氨酸）可能是一种潜在的药物。本综述认为GlyT-1抑制剂是治疗精神分裂症的新型药物。
Multiple lines of evidence suggest that hypofunction of glutamatergic neurotransmission via N-methyl-D-aspartate (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.