Striatal and temporal cortical D2/D3 receptor occupancy by olanzapine and sertindole in vivo:: a [123I]epidepride single photon emission tomography (SPET) study
Striatal and temporal cortical D2/D3 receptor occupancy by olanzapine and sertindole in vivo:: a [123I]epidepride single photon emission tomography (SPET) study
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DOI：
10.1007/s002130000435
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发表时间：
2000-06-01
影响因子：
3.4
通讯作者：
Pilowsky, LS
中科院分区：
文献类型：
--
作者：
Bigliani, V;Mulligan, RS;Pilowsky, LS
理论基础：先前的研究表明氯氮平优先针对边缘皮质多巴胺系统，这可能有助于解释其锥体外系副作用（EPS）的缺乏和优越的治疗效果。目的：验证新型非典型抗精神病药物奥氮平在体内比纹状体D2/D3受体更大程度上占据颞皮质D3/D3受体的假设。方法：9例服用奥氮平的精神分裂症患者[n=5，平均（SD）年龄：32.5（6.5）岁；每日剂量：18.3 (2.6)mg)或sertindole [(n=4)：平均（SD）年龄：30.3（7.4）岁；用[I-123]表皮pride （S)- n -[（1-乙基-2 -吡啶基）甲基]-5-碘-2,3-二甲氧基苯甲酰胺）和单光子发射断层扫描（SPET）研究日剂量：16 (5.6)mg。在患者和年龄匹配的健康志愿者中获得了[I-123]表皮自豪感与D2/D3受体的“特异性结合”的估计。总结了抗精神病药物对纹状体和颞叶皮层相对D3/D3受体占用率的影响。将占用数据与先前研究的接受典型抗精神病药物（n=12）和氯氮平（n=10）的患者组进行比较。结果：奥氮平治疗患者纹状体和颞皮质D2/D3受体的平均占用率分别为41.3% （SD 17.9）和82.8% （SD 4.2）。在两例典型的抗精神病药物引起的运动障碍患者中，在改用奥氮平之前，纹状体相对D2/D3受体占用率出乎意料地低。在颞叶皮层中，所有抗精神病药物的D2/D3多巴胺受体平均占用率均高于80%。结论：非典型抗精神病药物奥氮平和舍替多尔与氯氮平一样，在临床有效剂量下，颞皮质多巴胺受体的占用率高于纹状体D2/D3多巴胺受体。这可能有助于调解他们的治疗效果的非典型临床概况，很少锥体外系的副作用。边缘选择性阻断D2/D3多巴胺受体可能是非典型抗精神病药物的共同作用。
Rationale: Previous work suggests clozapine preferentially targets limbic cortical dopamine systems, which could help account for its lack of extrapyramidal side effects (EPS) and superior therapeutic efficacy. Objectives: To test the hypothesis that olanzapine, a novel atypical antipsychotic drug, occupies temporal cortical D3/D3 receptors to a greater extent than striatal D2/D3 receptors in vivo. Methods: Nine schizophrenic patients taking either olanzapine [(n=5: mean (SD) age: 32.5 (6.5) years; daily dose: 18.3 (2.6) mg)] or sertindole [(n=4: mean (SD) age: 30.3 (7.4) years; daily dose: 16 (5.6) mg] were studied with [I-123]epidepride (S)-N-[(1-ethyl- 2-pyrrolidinyl)methyl]-5-iodo-2,3-dimethoxy-benzamide) and single photon emission tomography (SPET). An estimate of [I-123]epidepride 'specific binding' to D2/D3 receptors was obtained in patients and age-matched healthy volunteers. A summary measure was generated representing striatal and temporal cortical relative %D3/D3 receptor occupancy by antipsychotic drugs. Occupancy data were compared with previously studied groups of patients receiving typical antipsychotic drugs (n=12) and clozapine (n=10). Results: Mean striatal and temporal cortical %D2/D3 receptor occupancy in olanzapine-treated patients was 41.3% (SD 17.9) and 82.8% (SD 4.2), respectively. Unexpectedly low levels of striatal relative %D2/D3 receptor occupancy were seen in two patients with typical antipsychotic-drug-induced movement disorder prior to switching to olanzapine. In the temporal cortex, mean D2/D3 dopamine receptor occupancy levels above 80% were seen for all antipsychotic drugs studied. Conclusions: The atypical antipsychotic drugs olanzapine and sertindole, in common with clozapine, demonstrate higher occupancy of temporal cortical than striatal D2/D3 dopamine receptors in vivo at clinically useful doses. This could help mediate their atypical clinical profile of therapeutic efficacy with few extrapyramidal side effects. Limbic selective blockade of D2/D3 dopamine receptors could be a common action of atypical antipsychotic drugs.