PATHOLOGICAL-CHANGES INDUCED IN CEREBROCORTICAL NEURONS BY PHENCYCLIDINE AND RELATED DRUGS
PATHOLOGICAL-CHANGES INDUCED IN CEREBROCORTICAL NEURONS BY PHENCYCLIDINE AND RELATED DRUGS
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DOI：
10.1126/science.2660263
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发表时间：
1989-06-16
期刊：
影响因子：
56.9
通讯作者：
PRICE, MT
中科院分区：
文献类型：
--
作者：
OLNEY, JW;LABRUYERE, J;PRICE, MT
苯环利定（PCP）是一种被广泛滥用的精神模拟药物，MK-801是一种强效的PCP受体配体，具有神经保护作用，可拮抗内源性兴奋性氨基酸如谷氨酸和天冬氨酸的兴奋毒性作用。人们对这些化合物在治疗神经系统疾病中的潜在应用越来越感兴趣。然而，PCP和相关药物（MK-801、替来他明和氯胺酮）具有明显的神经毒性作用，这一点迄今为止一直被忽视：当以相对低的剂量皮下注射给药于成年大鼠时，这些药物会诱导特定脑神经元群体的急性病理形态学变化。这些发现提出了关于这些药物在神经退行性疾病临床管理中的安全性的新问题，并加强了对非法使用五氯苯酚相关潜在风险的担忧。
Phencyclidine (PCP), a dissociative anesthetic and widely abused psychomimetic 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.