Olney J W, Farber N B
Department of Psychiatry, Washington University School of Medicine, St Louis, MO 63110.
J Clin Psychiatry. 1994 Sep;55 Suppl B:43-6.
The focus of this article will be on toxic symptoms associated with blockade of the N-methyl-D-aspartate (NMDA) subtype of the glutamate receptor. We have been studying two parallel phenomena: NMDA-antagonist neurotoxicity (NAN) in rats and NMDA-antagonist psychotogenicity (NAP) in humans. These phenomena have a common denominator--NMDA receptor hypofunction, which is putatively a mechanism operative in schizophrenia. We have found that the NAN reaction in rats can be prevented by specific drugs that prevent NAP in humans and by certain antipsychotic agents, including clozapine, that ameliorate symptoms in schizophrenia. By studying mechanisms by which clozapine prevents the NAN reaction in rats, we hope to gain insight into mechanisms by which clozapine or other atypical antipsychotics ameliorate symptoms in schizophrenia.
本文的重点将是与谷氨酸受体的N-甲基-D-天冬氨酸（NMDA）亚型阻断相关的毒性症状。我们一直在研究两个平行的现象：大鼠中的NMDA拮抗剂神经毒性（NAN）和人类中的NMDA拮抗剂致幻性（NAP）。这些现象有一个共同的特征——NMDA受体功能减退，这被认为是精神分裂症中起作用的一种机制。我们发现，大鼠中的NAN反应可以通过预防人类NAP的特定药物以及某些改善精神分裂症症状的抗精神病药物（包括氯氮平）来预防。通过研究氯氮平预防大鼠NAN反应的机制，我们希望深入了解氯氮平或其他非典型抗精神病药物改善精神分裂症症状的机制。
