NMDA receptor antagonist effects, cortical glutamatergic function, and schizophrenia: toward a paradigm shift in medication development
NMDA receptor antagonist effects, cortical glutamatergic function, and schizophrenia: toward a paradigm shift in medication development
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DOI：
10.1007/s00213-003-1582-z
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发表时间：
2003-09-01
影响因子：
3.4
通讯作者：
Hoffman, R
中科院分区：
文献类型：
--
作者：
Krystal, JH;D'Souza, DC;Hoffman, R
尽管引入了重要的新药物，但仍迫切需要改进精神分裂症的药物治疗。新的治疗见解可能来自对模型精神病治疗意义的认识。特别是，基础和临床研究已采用 N-甲基-D-天冬氨酸 (NMDA) 谷氨酸受体拮抗剂氯胺酮作为 NMDA 受体对认知和行为贡献的探针。这些研究说明了一种转化神经科学方法，用于探索与神经生物学和精神分裂症及其他疾病治疗相关的机制假设。与精神分裂症相关的两个特定的病理生理学主题，即皮质连接的紊乱和谷氨酸能活性的去抑制，可以通过施用 NMDA 受体拮抗剂来模拟。本综述的目的是考虑减弱 NMDA 受体拮抗剂反应的这两种成分的药物在精神分裂症的治疗中可能发挥互补作用的可能性。
There is an urgent need to improve the pharmacotherapy of schizophrenia despite the introduction of important new medications. New treatment insights may come from appreciating the therapeutic implications of model psychoses. In particular, basic and clinical studies have employed the N-methyl-D-aspartate (NMDA) glutamate receptor antagonist, ketamine, as a probe of NMDA receptor contributions to cognition and behavior. These studies illustrate a translational neuroscience approach for probing mechanistic hypotheses related to the neurobiology and treatment of schizophrenia and other disorders. Two particular pathophysiologic themes associated with schizophrenia, the disturbance of cortical connectivity and the disinhibition of glutamatergic activity may be modeled by the administration of NMDA receptor antagonists. The purpose of this review is to consider the possibility that agents that attenuate these two components of NMDA receptor antagonist response may play complementary roles in the treatment of schizophrenia.