Memantine, an n-methyl-d-aspartate (NMDA) receptor antagonist approved for treating Alzheimer’s disease, has a good safety profile and is increasingly being studied for possible use in a variety of non-dementia psychiatric disorders. There is an abundance of basic and clinical data that support the hypothesis that NMDA receptor hypofunction contributes to the pathophysiology of schizophrenia. However, there are numerous randomized, double-blind, placebo-controlled clinical trials showing that add-on treatment with memantine improves negative and cognitive symptoms, particularly the negative symptoms of schizophrenia, indicating that memantine as adjunctive therapy in schizophrenia helps to ameliorate negative symptoms and cognitive deficits. It remains unclear why memantine does not show undesirable central nervous system (CNS) side effects in humans unlike other NMDA receptor antagonists, such as phencyclidine and ketamine. However, the answer could lie in the fact that it would appear that memantine works as a low-affinity, fast off-rate, voltage-dependent, and uncompetitive antagonist with preferential inhibition of extrasynaptic receptors. It is reasonable to assume that the effects of memantine as adjunctive therapy on negative symptoms and cognitive deficits in schizophrenia may derive primarily, if not totally, from its NMDA receptor antagonist activity at NMDA receptors including extrasynaptic receptors in the CNS.

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美金刚作为 NMDA 受体拮抗剂在精神分裂症的辅助治疗中是否有效？

美金刚胺-甲基-d-天冬氨酸 (NMDA) 受体拮抗剂被批准用于治疗阿尔茨海默氏病，具有良好的安全性，并且越来越多地被研究用于治疗各种非痴呆性精神疾病。有大量基础和临床数据支持 NMDA 受体功能减退导致精神分裂症病理生理学的假设。然而，有许多随机、双盲、安慰剂对照的临床试验表明，美金刚的附加治疗可改善阴性症状和认知症状，尤其是精神分裂症的阴性症状，表明美金刚作为精神分裂症的辅助治疗有助于改善阴性症状和认知缺陷。与其他 NMDA 受体拮抗剂（例如苯环利定和氯胺酮）不同，美金刚在人体中没有表现出不良的中枢神经系统 (CNS) 副作用的原因尚不清楚。然而，答案可能在于美金刚胺似乎是一种低亲和力、快速解离速率、电压依赖性和非竞争性拮抗剂，优先抑制突触外受体。可以合理地假设，美金刚作为辅助疗法对精神分裂症的阴性症状和认知缺陷的影响可能主要（如果不是完全）来自其 NMDA 受体拮抗剂活性，包括 CNS 中的突触外受体。答案可能在于美金刚胺似乎是一种低亲和力、快速解离速率、电压依赖性和非竞争性拮抗剂，优先抑制突触外受体。可以合理地假设，美金刚作为辅助疗法对精神分裂症的阴性症状和认知缺陷的影响可能主要（如果不是完全）来自其 NMDA 受体拮抗剂活性，包括 CNS 中的突触外受体。答案可能在于美金刚胺似乎是一种低亲和力、快速解离速率、电压依赖性和非竞争性拮抗剂，优先抑制突触外受体。可以合理地假设，美金刚作为辅助疗法对精神分裂症的阴性症状和认知缺陷的影响可能主要（如果不是完全）来自其 NMDA 受体拮抗剂活性，包括 CNS 中的突触外受体。