@inproceedings{oai:repo.qst.go.jp:00054342,
 author = {Ito, Hiroshi and Takano, Harumasa and Arakawa, Ryosuke and Takahata, Keisuke and Kodaka, Fumitoshi and Takahashi, Hidehiko and Suhara, Tetsuya and 伊藤 浩 and 高野 晴成 and 荒川 亮介 and 高畑 圭輔 and 小高 文聰 and 高橋 英彦 and 須原 哲也},
 book = {Journal of Cerebral Blood Flow and Metabolism},
 issue = {Supplement 1},
 month = {Aug},
 note = {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.},
 pages = {S42--S43},
 title = {Effects of the partial agonist antipsychotic on dopamine synthesis capacity in human brain measured by PET with [C-11]DOPA},
 volume = {32},
 year = {2012}
}