Olney J W, Labruyere J, Price M T
Department of Psychiatry, Washington University School of Medicine, St. Louis, MO 63110.
Science. 1989 Jun 16;244(4910):1360-2. doi: 10.1126/science.2660263.
Phencyclidine (PCP), a dissociative anesthetic and widely abused psychotomimetic drug, and MK-801, a potent PCP receptor ligand, have neuroprotective properties stemming from their ability to antagonize the excitotoxic actions of endogenous excitatory amino acids such as glutamate and aspartate. There is growing interest in the potential application of these compounds in the treatment of neurological disorders. However, there is an apparent neurotoxic effect of PCP and related agents (MK-801, tiletamine, and ketamine), which has heretofore been overlooked: these drugs induce acute pathomorphological changes in specific populations of brain neurons when administered subcutaneously to adult rats in relatively low doses. These findings raise new questions regarding the safety of these agents in the clinical management of neurodegenerative diseases and reinforce concerns about the potential risks associated with illicit use of PCP.
苯环己哌啶（PCP）是一种分离麻醉剂，也是一种广泛滥用的拟精神病药物，而MK-801是一种强效的PCP受体配体，它们具有神经保护特性，源于其能够拮抗内源性兴奋性氨基酸（如谷氨酸和天冬氨酸）的兴奋性毒性作用。人们对这些化合物在治疗神经疾病方面的潜在应用越来越感兴趣。然而，PCP及相关药物（MK-801、替来他明和氯胺酮）存在一种明显的神经毒性作用，而这一点此前一直被忽视：当以相对低的剂量皮下注射给成年大鼠时，这些药物会在特定的脑神经元群体中引起急性病理形态学变化。这些发现就这些药物在神经退行性疾病临床管理中的安全性提出了新问题，并强化了对与非法使用PCP相关潜在风险的担忧。
