Impact of schizophrenia and chronic antipsychotic treatment on [123I]CNS-1261 binding to N-methyl-D-aspartate receptors in vivo
Impact of schizophrenia and chronic antipsychotic treatment on [123I]CNS-1261 binding to N-methyl-D-aspartate receptors in vivo
复制标题
DOI：
10.1016/j.biopsych.2005.03.016
复制
发表时间：
2005-07-01
影响因子：
10.6
通讯作者：
Pilowsky, LS
中科院分区：
文献类型：
--
作者：
Bressan, RA;Erlandsson, K;Pilowsky, LS
背景：抗精神病药物调节动物N-甲基-D-天冬氨酸（NMDA）受体功能。新型单光子发射断层扫描（SPET）放射性示踪剂[I-123]CNS-1261与NMDA受体的PCP/MK-801通道内位点结合，可无创估计活体人体中的NMDA受体活性。我们使用[I-123]CNS-1261来确定与NMDA受体通道内PCP/MK-801位点的结合是否受到精神分裂症或典型抗精神病药和氯氮平体内治疗的影响。三组精神分裂症患者均为招募-无药物组（n = 5），典型抗精神病药物治疗组（n = 7），氯氮平治疗组（n = 9）和健康志愿者对照组（n = 13）。所有患者均接受[I-123]CNS-1261 SPET扫描。[I-123]CNS-1261的总分布体积在所有图像与一个共同的模板对齐后，在预定义的用户无关的感兴趣区域内确定：[I-123]CNS-1261在无药物患者中的总分布体积相对于健康对照受试者没有明显差异。在典型的抗精神病药物治疗患者中观察到总分布容积无显著性降低。与健康对照受试者相比，在氯氮平治疗的患者组中，在所有检查的脑区域中观察到[I-123]CNS-1261的总分布体积显著下降（p < .005）。结论：氯氮平治疗导致体内[I-123]CNS-1261与NMDA受体通道内PCP/MK-801位点结合的总体减少。这支持了药物对多巴胺能系统的作用，可用于未来的抗精神病药物发现。
Background: Antipsychotic drugs modulate N-methyl-D-aspartate (NMDA) receptor function in animals. The novel single photon emission tomography (SPET) radiotracer [I-123]CNS-1261 binds to the PCP/MK-801 intrachannel site of the NMDA receptor, allowing the noninvasive estimation of NMDA receptor activity in living humans. We used [I-123]CNS-1261 to determine whether binding to the NMDA receptor intrachannel PCP/MK-801 site is affected by schizophrenia or by treatment with typical antipsychotics and clozapine in vivo.Methods: Three groups of schizophrenia patients were recruited-drug free (n = 5), typical antipsychotic treated (n = 7), and clozapine treated (n = 9)-as well as a control group of healthy normal volunteers (n = 13). All underwent [I-123]CNS-1261 SPET scanning. Total volume of distribution of [I-123]CNS-1261 was determined within predefined user-independent regions of interest after alignment of all images to a common template.Results: There was no apparent difference in total volume of distribution of [I-123]CNS-1261 in drug-free patients relative to healthy control subjects. A nonsignificant reduction in total volume of distribution was observed in typical antipsychotic treated patients. A significant decline in total volume of distribution of [I-123]CNS-1261 was observed in all examined brain regions in the clozapine-treated patient group relative to healthy control subjects (p < .005).Conclusions: Clozapine treatment resulted in a global reduction in [I-123]CNS-1261 binding to the NMDA receptor intrachannel PCP/MK-801 site in vivo. This supports an effect of the drug on glutamatergic systems that could be exploited for future antipsychotic drug discovery.