The NMDA receptor glycine modulatory site: a therapeutic target for improving cognition and reducing negative symptoms in schizophrenia
The NMDA receptor glycine modulatory site: a therapeutic target for improving cognition and reducing negative symptoms in schizophrenia
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DOI：
10.1007/s00213-003-1709-2
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发表时间：
2004-06-01
影响因子：
3.4
通讯作者：
Tsai, G
中科院分区：
文献类型：
--
作者：
Coyle, JT;Tsai, G
大量临床研究表明，麻醉下剂量的解离麻醉剂是NMDA受体上的非竞争性拮抗剂，在正常受试者中复制精神分裂症的认知障碍、阴性症状和脑功能异常。尸检和遗传学研究已经发现了几种与精神分裂症相关的异常，这些异常会干扰NMDA受体上甘氨酸调节位点的激活。使用直接或间接激活甘氨酸调节位点的药物进行的安慰剂对照临床试验持续减少慢性精神分裂症患者的阴性症状，并经常改善认知能力，这些患者同时接受典型的抗精神病药物治疗。因此，有令人信服的证据表明，NMDA受体上的甘氨酸调节位点是改善精神分裂症认知和相关阴性症状的有效治疗靶点。
Numerous clinical studies demonstrate that subanaesthetic doses of dissociative anaesthetics, which are non-competitive antagonists at the NMDA receptor, replicate in normal subjects the cognitive impairments, negative symptoms and brain functional abnormalities of schizophrenia. Post-mortem and genetic studies have identified several abnormalities associated with schizophrenia that would interfere with the activation of the glycine modulatory site on the NMDA receptor. Placebo controlled clinical trials with agents that directly or indirectly activate the glycine modulatory site consistently reduce negative symptoms and frequently improve cognition in patients with chronic schizophrenia, who are receiving concurrent typical antipsychotics. Thus, there is convincing evidence that the glycine modulatory site on the NMDA receptor is a valid therapeutic target for improving cognition and associated negative symptoms in schizophrenia.