The atypical antipsychotic agents zisprasidone, risperdone and olanzapine as treatment for and prophylaxis against progressive multifocal leukoencephatopathy
The atypical antipsychotic agents zisprasidone, risperdone and olanzapine as treatment for and prophylaxis against progressive multifocal leukoencephatopathy
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DOI：
10.1016/j.mehy.2005.01.037
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发表时间：
2005-01-01
影响因子：
4.7
通讯作者：
Kast, RE
中科院分区：
文献类型：
--
作者：
Altschuler, EL;Kast, RE
进行性多灶性脑白质病（PML）是一种持续进行的中枢神经系统白色物质疾病。PML是由JC多瘤病毒感染引起的，最常见于因例如癌症、抗排斥移植药物或HIV而导致免疫抑制的患者。PML没有特定的治疗或治愈方法，未经治疗，其平均预期寿命不到四个月。高效抗逆转录病毒治疗（HAART）可能大大降低了HIV+患者PML的发病率和患病率，然而，即使在HIV+ PML患者接受HAART治疗的最佳情况下，死亡率仍然很高。需要新的PML治疗方法。最近Atwood和同事发现JC病毒的细胞受体是5-羟色胺5 HT 2（A）受体。在体外实验中，他们使用较老的抗精神病药物氯丙嗪和氯氮平来阻断5-羟色胺5 HT 2（A）受体并阻断JC病毒进入细胞。然而，不幸的是，氯丙嗪和氯氮平具有如此显著的副作用和毒性，例如，锥体外系症状和骨髓恶液质的可能性，它们在临床上使用可能有问题。在此，我们指出，一些较新的非典型抗精神病药物，如齐拉西酮、利培酮和奥氮平--这些药物的副作用和毒性比老的抗精神病药物好得多--在体外是比氯丙嗪或氯氮平更有效的5 HT 2（A）受体拮抗剂，在某些情况下超过10倍，因此可能用于治疗或预防PML。(c)2005爱思唯尔有限公司保留所有权利。
Progressive multifocal leukoencephalopathy (PML) is an unremitting, advancing disease of central nervous system white matter. PML is caused by infection of the JC polyoma virus, most always in patients with immunosupression due to, for example, cancer, anti-rejection transplant medications or HIV. There is no specific treatment or cure for PML, and untreated it has a median life expectancy is less than four months. Highly active antiretroviral treatment (HAART) has greatly reduced the incidence and prevalence of PML in HIV+ patients likely, however, even in the best case scenario of an HIV+ patient with PML and taking HAART, a significant mortality remains. Novel treatments for PML are needed. Recently Atwood and colleagues have found that the cellular receptor for JC virus is the serotonin 5HT2(A) receptor. In vitro they used the older antipsychotic medications chlorpromazine and clozapine to block the serotonin 5HT2(A) receptor and block JC virus cell entry. Unfortunately, however, chlorpromazine and clozapine have such significant side effects and toxicities, e.g., extrapyramidal symptoms and the possibility of bone marrow dyscrasias that they may be problematic to use clinically. Here, we point out that some newer atypical antipsychotics such as zisprasidone, risperidone and olanzapine - medicines with much better side effect and toxicity profiles than the older antipsychotics - in vitro are significantly more potent 5HT2(A) receptor antagonists than chlorpromazine or clozapine by in some cases more than a factor of 10, and thus may be useful as treatment for or prophylaxis against PML. (c) 2005 Elsevier Ltd. All rights reserved.