Effects of the Antipsychotic Risperidone on Dopamine Synthesis in Human Brain Measured by Positron Emission Tomography with L-[β-11C]DOPA: A Stabilizing Effect for Dopaminergic Neurotransmission?
Effects of the Antipsychotic Risperidone on Dopamine Synthesis in Human Brain Measured by Positron Emission Tomography with L-[β-11C]DOPA: A Stabilizing Effect for Dopaminergic Neurotransmission?
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DOI：
10.1523/jneurosci.4172-09.2009
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发表时间：
2009-10-28
影响因子：
5.3
通讯作者：
Suhara, Tetsuya
中科院分区：
文献类型：
--
作者：
Ito, Hiroshi;Takano, Harumasa;Suhara, Tetsuya
抗精神病药物的作用被广泛认为是通过阻断突触后多巴胺D-2受体介导的。抗精神病药物对多巴胺能神经传递突触前功能的影响也可能与抗精神病药物的疗效有关。为探讨抗精神病药物对多巴胺能神经传递突触前功能的影响及其与多巴胺D-2受体占位的关系，采用正电子发射断层扫描（PET）技术测定了健康男性多巴胺合成能力和多巴胺D-2受体占位的变化。使用[C-11]雷氯必利和L-[β-C-11]多巴的PET研究在静息状态下进行，并在不同的日子口服单剂量的抗精神病药物利培酮。虽然观察到多巴胺D-2受体的占有率与利培酮的剂量相对应，但利培酮给药引起的多巴胺合成能力的变化并不显著，多巴胺D-2受体的占有率与这些变化之间的关系也不显著。在基线多巴胺合成能力和利培酮引起的多巴胺合成能力变化之间观察到显著负相关，表明这种抗精神病药可以稳定多巴胺合成能力。利培酮对精神分裂症的治疗作用可能与其稳定多巴胺能神经传递反应性有关。
Effects of antipsychotic drugs have widely been considered to be mediated by blockade of postsynaptic dopamine D-2 receptors. Effects of antipsychotics on presynaptic functions of dopaminergic neurotransmission might also be related to therapeutic effects of antipsychotics. To investigate the effects of antipsychotics on presynaptic functions of dopaminergic neurotransmission in relation with occupancy of dopamine D-2 receptors, changes in dopamine synthesis capacity by antipsychotics and occupancy of dopamine D-2 receptors were measured by positron emission tomography (PET) in healthy men. PET studies using [C-11] raclopride and L-[beta-C-11] DOPA were performed under resting condition and oral administration of single dose of the antipsychotic drug risperidone on separate days. Although occupancy of dopamine D-2 receptors corresponding dose of risperidone was observed, the changes in dopamine synthesis capacity by the administration of risperidone were not significant, nor was the relation between the occupancy of dopamine D-2 receptors and these changes. A significant negative correlation was observed between the baseline dopamine synthesis capacity and the changes in dopamine synthesis capacity by risperidone, indicating that this antipsychotic can be assumed to stabilize the dopamine synthesis capacity. The therapeutic effects of risperidone in schizophrenia might be related to such stabilizing effects on dopaminergic neurotransmission responsivity.