What proportion of striatal D2 receptors are occupied by endogenous dopamine at baseline? A meta-analysis with implications for understanding antipsychotic occupancy
What proportion of striatal D2 receptors are occupied by endogenous dopamine at baseline? A meta-analysis with implications for understanding antipsychotic occupancy
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DOI：
10.1016/j.neuropharm.2019.03.034
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发表时间：
2020-02-01
影响因子：
4.7
通讯作者：
Graff-Guerrero，Ariel
中科院分区：
文献类型：
--
作者：
Caravaggio，Fernando;Iwata，Yusuke;Graff-Guerrero，Ariel
使用分子成像技术-正电子发射断层扫描(PET)和单光子发射计算机断层扫描(SPECT)-结合急性多巴胺耗竭挑战(α-甲基-对酪氨酸)，有可能估计在人体内占据纹状体多巴胺D2受体(D2R)的内源性多巴胺水平。然而，在正常情况下，内源性多巴胺在纹状体D2R中所占的比例尚不清楚。这一点很重要，因为有研究表明，在精神分裂症患者中，可能有相当大比例的纹状体D2R被内源性多巴胺占据，而不能通过治疗剂量的抗精神病药物获得。为了阐明这些问题，我们使用取代苯甲酰胺放射性示踪剂对健康人进行了多巴胺耗竭研究的荟萃分析。这一荟萃分析表明，基线时纹状体D2R的8%至21%(加权平均11%)可能被内源性多巴胺占据。利用这些估计，我们提出了一个更新的占有率模型，并初步提出抗精神病药物抑制纹状体D2R活体总池的比例比之前承认的更小。本文是题为《抗精神病药物特刊》的一部分。
Using molecular imaging techniques – positron emission tomography (PET) and single-photon emission computed tomography (SPECT) – in conjunction with an acute dopamine depletion challenge (alpha-methyl-para-tyrosine) it is possible to estimate endogenous dopamine levels occupying striatal dopamine D2receptors (D2R) in humansin vivo. However, it is unclear what proportion of striatal D2R are occupied by endogenous dopamine under normal conditions. This is important since it has been suggested that in schizophrenia there may be a substantial proportion of striatal D2R which are occupied by endogenous dopamine and not accessible by therapeutic doses of antipsychotics. In order to clarify these issues, we conducted a meta-analysis of dopamine depletion studies using substituted benzamide radiotracers in healthy persons. This meta-analysis suggests that anywhere from 8 to 21% (weighted average 11%) of striatal D2R may be occupied by endogenous dopamine at baseline. Using these estimates, we propose an updated occupancy model and tentatively suggest that antipsychotics inhibit a smaller proportion of the total pool of striatal D2Rin vivothan previously acknowledged.This article is part of the issue entitled ‘Special Issue on Antipsychotics’.