Positron Emission Tomography Measurement of Dopamine D2 Receptor Occupancy in the Pituitary and Cerebral Cortex: Relation to Antipsychotic-Induced Hyperprolactinemia
Positron Emission Tomography Measurement of Dopamine D2 Receptor Occupancy in the Pituitary and Cerebral Cortex: Relation to Antipsychotic-Induced Hyperprolactinemia
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DOI：
10.4088/jcp.08m04307yel
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发表时间：
2010-09-01
影响因子：
5.3
通讯作者：
Suhara, Tetsuya
中科院分区：
文献类型：
--
作者：
Arakawa, Ryosuke;Okumura, Masaki;Suhara, Tetsuya
目的：高催乳素血症是治疗精神分裂症的抗精神病药物的常见副作用。然而，抗精神病药物中高催乳素血症的严重程度不同，并且没有可靠的机制相关标志物来描述高催乳素血症的风险，使我们能够表征抗精神病药物。 方法：在这项研究中，11 名健康男性受试者服用不同剂量的舒必利，24 名患有 DSM-IV 诊断的精神分裂症男性患者服用不同的抗精神病药物（利培酮、奥氮平、氟哌啶醇和舒必利）参加。使用 [C-11] FLB 457 对所有受试者进行正电子发射断层扫描。计算抗精神病药在垂体和颞叶皮层中多巴胺 D-2 受体的占用率。评估了催乳素血浆浓度和多巴胺 D-2 受体占用率之间的相关性。根据2个区域的受体占有率计算脑受体位点与垂体受体位点的药物浓度比（脑/血浆浓度比；B/P比）。数据收集于 2001 年 11 月至 2007 年 9 月之间。 结果：所有 4 种抗精神病药的催乳素血浆浓度与垂体多巴胺 D-2 受体占用率之间均观察到显着正相关 (P = .001)。舒必利的多巴胺 D-2 受体占用率在垂体和颞叶皮质之间存在显着差异，舒必利的 B/P 比 (0.34) 显着低于奥氮平 (P = .007) 和利培酮 (P = .015)。奥氮平的 B/P 比值相对较高（2.70），其次是氟哌啶醇（2.40）和利培酮（1.61）。结论：垂体中多巴胺 D-2 受体的占用是高催乳素血症的良好指标。 B/P 比值表明穿过血脑屏障的穿透能力，似乎是每种抗精神病药物在治疗剂量下发生高催乳素血症风险的良好特征生物标志物。 J Clin Psychiatry 2010；71(9):1131 1137 (C) 版权所有 2010 Physicians Postgraduate Press, Inc.
Objective: Hyperprolactinemia is a common side effect of antipsychotic drugs used in the treatment of schizophrenia. However, the magnitude of hyperprolactinemia differs among antipsychotics, and there is no reliable mechanism-related marker for the risk of hyperprolactinemia that would allow us to characterize antipsychotics.Method: In this study, 11 healthy male subjects taking different doses of sulpiride and 24 male patients with DSM-IV-diagnosed schizophrenia taking different antipsychotic drugs (risperidone, olanzapine, haloperidol, and sulpiride) participated. Positron emission tomography scanning using [C-11] FLB 457 was performed on all subjects. The dopamine D-2 receptor occupancy of antipsychotics in the pituitary and temporal cortex was calculated. Correlations between plasma concentration of prolactin and dopamine D-2 receptor occupancies were evaluated. The ratio of drug concentration of cerebral receptor site to that of pituitary receptor site (brain/plasma concentration ratio; B/P ratio) was calculated from the receptor occupancies in the 2 regions. Data were collected between November 2001 and September 2007.Results: Significant positive correlation was observed between the plasma concentration of prolactin and dopamine D-2 receptor occupancy in the pituitary by all 4 antipsychotics (P = .001). Dopamine D-2 receptor occupancies of sulpiride were markedly different between the pituitary and temporal cortex, and the B/P ratio for sulpiride (0.34) was significantly lower than for olanzapine (P = .007) and risperidone (P = .015). Olanzapine had a relatively high B/P ratio (2.70), followed by haloperidol (2.40) and risperidone (1.61).Conclusions: Dopamine D-2 receptor occupancy in the pituitary is a good indicator of hyperprolactinemia. B/P ratio, indicating the penetrating capability across the blood-brain barrier, seems to be a good characteristic biomarker of each antipsychotic drug for the risk of hyperprolactinemia at therapeutic dose. J Clin Psychiatry 2010;71(9):1131 1137 (C) Copyright 2010 Physicians Postgraduate Press, Inc.