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Effects of the Partial Agonist Antipsychotic on Dopamine Synthesis Capacity in Human Brain Measured by PET with [C-11]DOPA
https://repo.qst.go.jp/records/70851
https://repo.qst.go.jp/records/70851cc6df16f-d98b-46c5-bc93-b394dfbb8ea2
| Item type | 会議発表用資料 / Presentation(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2012-08-17 | |||||
| タイトル | ||||||
| タイトル | Effects of the Partial Agonist Antipsychotic on Dopamine Synthesis Capacity in Human Brain Measured by PET with [C-11]DOPA | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_c94f | |||||
| 資源タイプ | conference object | |||||
| アクセス権 | ||||||
| アクセス権 | metadata only access | |||||
| アクセス権URI | http://purl.org/coar/access_right/c_14cb | |||||
| 著者 |
Ito, Hiroshi
× Ito, Hiroshi× Takano, Harumasa× Arakawa, Ryosuke× Takahata, Keisuke× Kodaka, Fumitoshi× Takahashi, Hidehiko× Suhara, Tetsuya× 伊藤 浩× 高野 晴成× 荒川 亮介× 高畑 圭輔× 小高 文聰× 高橋 英彦× 須原 哲也 |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Background: The partial agonist antipsychotic drugs of dopamine D2 receptors can modulate dopaminergic neurotransmission as functional agonists or functional antagonists. Effects of antipsychotics on the presynaptic functions of dopaminergic neurotransmission might also be related to their therapeutic effects. Recently, we found that the antagonist antipsychotic drug risperidone can be considered to stabilize dopamine synthesis capacity in healthy human subjects [1]. In the present study, changes in dopamine synthesis capacity by the partial agonist antipsychotic drug aripiprazole were measured by PET. \nMethods: PET studies were performed on 12 healthy men under resting condition (baseline study) and oral administration of single dose of aripiprazole of 3–9 mg, (drug challenge study) on separate days. In each study, both PET scans with [C-11]raclopride and [C-11]DOPA were performed sequentially. The occupancy of dopamine D2 receptors by aripiprazole was calculated from binding potential values in the striatum for baseline and drug challenge studies with [C-11]raclopride determined by the SRTM method using the cerebellum as a reference region. The uptake rate constant, Ki, for [C-11]DOPA in the striatum indicating the dopamine synthesis capacity was estimated by graphical analysis using the occipital cortex as a reference region. \nResults: The occupancies of dopamine D2 receptors were 53%-77%. The dopamine synthesis capacity Ki were 0.0128+-0.0016 and 0.0128+-0.0014 (1/min) for the baseline and drug challenge studies, respectively, and no significant change in Ki by aripiprazole was observed. No significant correlation between occupancies of dopamine D2 receptors and changes in Ki by aripiprazole was observed. A significant negative correlation was observed between the baseline Ki and the change in Ki by aripiprazole (r-0.65). The plasma concentrations of aripiprazole during [C-11]raclopride and [C-11]DOPA PET studies ranged from 9.3 to 40.4ng/mL (23.7+-11.3ng/mL, mean+-SD) and from 9.1 to 39.7ng/mL (21.5+-11.0ng/mL), respectively. \nConclusion: The negative correlation between the baseline Ki and the change in Ki by aripiprazole, and smaller coefficient of variation of Ki in drug challenge studies than in baseline studies indicate that aripiprazole can be assumed to stabilize the level of dopamine synthesis capacity same as antagonist antipsychotic drugs. An abnormal responsivity in both phasic and tonic dopamine release, which might be related to the modulation of dopaminergic neurotransmission, has been considered in the pathophysiology of schizophrenia [2]. Therapeutic effects of aripiprazole on schizophrenia might be related to stabilizing effects on dopaminergic neurotransmission responsivity in dopamine release. \nReferences \n[1] Ito H et al. Effects of the antipsychotic risperidone on dopamine synthesis in human brain measured by positron emission tomography with L-[beta-C-11]DOPA: a stabilizing effect for dopaminergic neurotransmission? J Neurosci 29:13730-13734, 2009. \n[2] Grace AA. Phasic versus tonic dopamine release and the modulation of dopamine system responsivity: a hypothesis for the etiology of schizophrenia. Neuroscience 41:1-24, 1991. |
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| 会議概要（会議名, 開催地, 会期, 主催者等） | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | The 9th International Symposium on Functional Neuroreceptor Mapping of the Living Brain (NRM12) | |||||
| 発表年月日 | ||||||
| 日付 | 2012-08-11 | |||||
| 日付タイプ | Issued | |||||
