Ito Hiroshi, Takano Harumasa, Takahashi Hidehiko, Arakawa Ryosuke, Miyoshi Michie, Kodaka Fumitoshi, Okumura Masaki, Otsuka Tatsui, Suhara Tetsuya
Molecular Imaging Center, National Institute of Radiological Sciences, Inage-ku, Chiba, Japan.
J Neurosci. 2009 Oct 28;29(43):13730-4. doi: 10.1523/JNEUROSCI.4172-09.2009.
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 [(11)C]raclopride and L-[beta-(11)C]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.
抗精神病药物的作用广泛被认为是通过阻断突触后多巴胺D(2)受体来介导的。抗精神病药物对多巴胺能神经传递突触前功能的影响可能也与抗精神病药物的治疗效果有关。为了研究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)受体占有率的关系，通过正电子发射断层扫描（PET）在健康男性中测量了抗精神病药物对多巴胺合成能力的影响以及多巴胺D(2)受体的占有率。在静息状态下以及在不同日期口服单剂量抗精神病药物利培酮后，使用[(11)C]雷氯必利和L-[β-(11)C]多巴进行PET研究。尽管观察到了与利培酮相应剂量的多巴胺D(2)受体占有率，但利培酮给药后多巴胺合成能力的变化并不显著，多巴胺D(2)受体占有率与这些变化之间也没有关系。在基线多巴胺合成能力与利培酮引起的多巴胺合成能力变化之间观察到显著的负相关，这表明可以认为这种抗精神病药物能够稳定多巴胺合成能力。利培酮在精神分裂症中的治疗效果可能与对多巴胺能神经传递反应性的这种稳定作用有关。
