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EFFECTS OF SECOND-GENERATION ANTIPSYCHOTIC DRUG ON DOPAMINE SYNTHESIS IN HUMAN BRAIN MEASURED BY PET WITH L-[C-11]DOPA
https://repo.qst.go.jp/records/63135
https://repo.qst.go.jp/records/63135f578d871-2cd1-4083-b113-e47029a272d2
| Item type | 会議発表用資料 / Presentation(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2009-07-06 | |||||
| タイトル | ||||||
| タイトル | EFFECTS OF SECOND-GENERATION ANTIPSYCHOTIC DRUG ON DOPAMINE SYNTHESIS IN HUMAN BRAIN MEASURED BY PET WITH L-[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× Takahashi, Hidehiko× Arakawa, Ryosuke× Miyoshi, Michie× Kodaka, Fumitoshi× Okumura, Masaki× Otsuka, Tatsui× Suhara, Tetsuya× 伊藤 浩× 高野 晴成× 高橋 英彦× 荒川 亮介× 三好 美智恵× 小高 文聰× 奥村 正紀× 大塚 達以× 須原 哲也 |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Objectives: Effects of antipsychotic drugs have widely been considered to be mediated by blockade of dopamine D2 receptors. Effects of antipsychotics on presynaptic functions of dopaminergic neurotransmission might also be related to therapeutic effects of antipsychotics. In the present study, changes in dopamine synthesis rate by administration of single dose of second-generation antipsychotics in relation with occupancy of dopamine D2 receptors were measured by positron emission tomography (PET) in healthy human subjects. Methods: PET studies were performed on 12 healthy men (21-29 years of age) under resting condition (baseline study) and oral administration of single dose of antipsychotic drug, risperidone of 0.5-2.0 mg, (drug challenge study) on separate days. In each study, both PET scans with [C-11]raclopride and L-[C-11]DOPA were performed sequentially to measure dopamine D2 receptor binding and dopamine synthesis rate, respectively. For [C-11]raclopride PET, the binding potential (BP) in the striatum was calculated by the reference tissue model method with use of the cerebellum as a reference region. The occupancy of dopamine D2 receptors by risperidone was calculated from BP values in baseline and drug challenge studies. The uptake rate constant, Ki, for L-[C-11]DOPA in the striatum indicating the dopamine synthesis rate was estimated by the graphical analysis with use of the occipital cortex as a reference region [1]. The percentage change in Ki by risperidone was calculated from Ki values in baseline and drug challenge studies. Results: The occupancies of dopamine D2 receptors ranged from 39% to 75% in the putamen. The dopamine synthesis rate Ki values were 0.0136 +- 0.0017 (1/min) and 0.0142 +- 0.0010 (1/min) (mean +- SD) in the putamen for the baseline and drug challenge studies, respectively. While occupancy of dopamine D2 receptors corresponding dose of risperidone was observed, no significant change in dopamine synthesis rate by risperidone was observed. No significant correlation between the occupancy of dopamine D2 receptors and the change in dopamine synthesis rate by risperidone was also observed. On the other hand, a significant negative correlation was observed between the baseline dopamine synthesis rate and the change in dopamine synthesis rate by risperidone (r = -0.87, P < 0.001). Conclusions: The negative correlation between the baseline dopamine synthesis rate and the change in dopamine synthesis rate by risperidone, and smaller coefficient of variation of dopamine synthesis rate Ki in drug challenge studies than in baseline studies indicate that second-generation antipsychotic, risperidone, can be considered to stabilize the level of dopamine synthesis rate. The concept of phasic and tonic dopamine release with relation to the modulation of dopaminergic neurotransmission has been proposed, and abnormal responsivity in both the phasic and tonic dopamine release in schizophrenia have been considered [2]. Therapeutic effects of risperidone might be related to stabilizing effects on such dopaminergic neurotransmission responsivity. References: [1] Patlak CS, Blasberg RG. J Cereb Blood Flow Metab 1985; 5: 584-590. [2] Grace AA. Neuroscience 1991; 41: 1-24. | |||||
| 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 | Brain '09 & Brain PET '09 | |||||
| 発表年月日 | ||||||
| 日付 | 2009-07-03 | |||||
| 日付タイプ | Issued | |||||
