Department of Clinical and Theoretical Mental Health, Semmelweis University, Budapest, Hungary.
Curr Pharm Des. 2012;18(12):1558-67. doi: 10.2174/138161212799958521.
NMDA receptors are ionotropic receptors mediating glutamatergic neurotransmission and play a role in several basic functions in the central nervous system, from regulating neurodevelopment and synaptic plasticity, learning and memory formation, cognitive processes, rhythm generation necessary for locomotor activity and breathing, and excitotoxicity. Due to their complex involvement in the above processes, NMDA receptors have been established to play a role in the etiopathology of several neuropsychiatric disorders such as ischaemia and traumatic brain injury, neurodegenerative disorders, pain syndromes, addiction, affective disorders and such neurodevelopmental disorders as autism or schizophrenia. NMDA receptors contain multiple types of subunits with distinct functional and pharmacological properties making the picture more complex. These receptors also offer multiple binding sites to be targeted with pharmacons, however, early broad-spectrum NMDA receptor antagonists had limited clinical use due to their intolerable adverse effect profile. The discovery of several types of subunit selective NMDA receptor antagonists may offer valuable therapeutic possibilities for several disorders, with improved clinical efficacy and decreased side effects. However, in spite of our increasing knowledge concerning the involvement of NMDA receptors in pathological processes, molecules with a selective action, tolerable side effect profile and good clinical efficacy are still only in clinical development in the majority of cases. Nevertheless, NMDA receptors offer a novel opportunity in the treatment of various neuropsychiatric conditions.
NMDA 受体是离子型受体，介导谷氨酸能神经传递，在中枢神经系统的几个基本功能中发挥作用，从调节神经发育和突触可塑性、学习和记忆形成、认知过程、运动活动和呼吸所需的节律产生，以及兴奋性毒性。由于它们在上述过程中的复杂参与，NMDA 受体已被确定在几种神经精神疾病的病因发病机制中发挥作用，如缺血和创伤性脑损伤、神经退行性疾病、疼痛综合征、成瘾、情感障碍以及自闭症或精神分裂症等神经发育障碍。NMDA 受体包含具有不同功能和药理学特性的多种类型的亚基，使情况更加复杂。这些受体还提供了多个结合位点，可以用药物结合，然而，早期的广谱 NMDA 受体拮抗剂由于其不可耐受的不良作用谱，临床应用有限。几种类型的亚基选择性 NMDA 受体拮抗剂的发现可能为多种疾病提供有价值的治疗可能性，具有改善的临床疗效和降低的副作用。然而，尽管我们对 NMDA 受体在病理过程中的参与有了更多的了解，但具有选择性作用、可耐受的副作用谱和良好临床疗效的分子在大多数情况下仍处于临床开发阶段。尽管如此，NMDA 受体为治疗各种神经精神疾病提供了新的机会。
