Characterization of the serotonin transporter in lymphocytes and platelets of schizophrenia patients treated with atypical or typical antipsychotics compared to healthy individuals
Characterization of the serotonin transporter in lymphocytes and platelets of schizophrenia patients treated with atypical or typical antipsychotics compared to healthy individuals
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DOI：
10.1016/j.euroneuro.2005.11.008
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发表时间：
2006-08-01
影响因子：
5.6
通讯作者：
Rehavi, Moshe
中科院分区：
文献类型：
--
作者：
Barkan, Tal;Peled, Avi;Rehavi, Moshe
越来越多的数据表明，5-羟色胺能功能异常可能参与了精神分裂症的病理生理学，5-羟色胺能机制在抗精神病药物的治疗效果中发挥了作用。用[H-3]-5-羟色胺摄取法测定了38例精神分裂症患者(其中15例用典型抗精神病药物治疗，23例用非典型抗精神病药物治疗)和15例健康对照的5-羟色胺转运体(5-HTT)活性。此外，用[H-3]西酞普兰结合法评价了血小板5-羟色胺的药效学特征，三组之间的血小板[H-3]西酞普兰结合部位密度(B-max)无显著差异。同样，解离常数(K-d)值也是不可区分的。3组新鲜淋巴细胞对[H-3]5-羟色胺的最大摄取速度(V-max)差异无统计学意义。接受典型抗精神病药物治疗的精神分裂症患者5-羟色胺与5-羟色胺的亲和力(K-m)值显著高于对照组。接受非典型抗精神病药物治疗的精神分裂症患者的K-m值明显低于接受典型抗精神病药物治疗的精神分裂症患者，但与对照组接近。与典型抗精神病药物治疗相关的高K-m值可能与锥体外系副作用(EPS)的高风险有关。5-羟色胺能系统的各个组成部分在精神分裂症的病因中所占的比例以及抗精神病药物达到治疗效果的机制需要进一步评估。(C)2005年Elsevier B.V和ECNP。版权所有。
A rapidly growing body of data suggests that abnormalities in serotonergic function might be involved in the pathophysiology of schizophrenia and that serotonergic mechanisms play a role in the therapeutic effects of antipsychotics. The activity of the serotonin transporter (5-HTT), as determined by [H-3]5-HT uptake to blood lymphocytes, was measured in 38 medicated schizophrenia patients (15 of them treated with typical antipsychotics and 23 treated with atypical antipsychotics) and 15 healthy control subjects. In addition, the pharmacodynamic characteristics of platelet 5-HTT were assessed by [H-3]citalopram binding.There were no significant differences in the density (B-max) of platelet [H-3]citalopram binding sites between the three groups. Similarly, the dissociation constant (K-d) values were indistinguishable. There were no significant differences in the maximal uptake velocity (V-max) of [H-3]5-HT to fresh lymphocytes between the three groups. The affinity (K-m) values of 5-HT to the 5-HTT were significantly higher in schizophrenia patients treated with typical antipsychotics compared with control subjects. The K-m values in schizophrenia patients treated with atypical antipsychotics were significantly lower compared with those observed in the group of schizophrenia patients treated with typical antipsychotics; however, they were comparable to values in the control group. The high values of K-m associated with typical antipsychotic treatment may be relevant to the high risk of developing extrapyramidal side effects (EPS). The rote of the various components of the serotonergic system in the etiopathology of schizophrenia and the mechanisms by which antipsychotics achieve their therapeutic effects need to be further evaluated. (c) 2005 Elsevier B.V and ECNP. All rights reserved.