@misc{oai:repo.qst.go.jp:00071117,
 author = {Kimura, Yasuyuki and Ito, Hiroshi and Maeda, Jun and Yamada, Makiko and Fujiwara, Hironobu and Eguchi, Yoko and Seki, Chie and Kodaka, Fumitoshi and Takahata, Keisuke and Takano, Harumasa and Ikoma, Youko and Minamimoto, Takafumi and Higuchi, Makoto and Suhara, Tetsuya and 木村 泰之 and 伊藤 浩 and 前田 純 and 山田 真希子 and 藤原 広臨 and 江口 洋子 and 関 千江 and 小高 文聰 and 高畑 圭輔 and 高野 晴成 and 生駒 洋子 and 南本 敬史 and 樋口 真人 and 須原 哲也},
 month = {May},
 note = {Regional alterations in extracellular dopamine levels can be observed in the striatum during performance of neuropsychological tasks using PET1. To increase detection of the alteration, dopamine reuptake inhibitor could be useful for producing a greater magnitude of change in 11C-raclopride binding2. Mazindol is a non-selective catecholamine reuptake inhibitor, which blocks dopamine reuptake and thus could be used as an enhancer of dopamine release by neuropsyhological tasks3. To investigate basic potency of mazindol in human, we measured occupancy of the dopamine transporter and change in 11C-raclopride binding using PET after single oral administration of mazindol.
Methods:
Two sets of PET scans were acquired on six healthy volunteers after oral administration of placebo and 1.5 mg of mazindol. 11C-raclopride was injected at 3 hours after the administration of placebo or mazindol, and 18F-FE-PE2I was injected at 5 hours. In the brain, preset volumes of interest were applied on the spatially normalized PET images. Binding potential of sub-regions of striatum was calculated by the simplified reference tissue model using cerebellum as reference region. Dopamine transporter occupancy was calculated by the % change of the binding potential of 18F-FE-PE2I, and change in extracellular dopamine levels was measured by the % change of that of 11C-raclopride.
Results:
After oral administration of 1.5 mg of mazindol, the binding potential of 18F-FE-PE2I significantly reduced by 20 &#8211; 25 % (p < 0.01, paired t-test), indicating 20 &#8211; 25 % of dopamine transporters in the striatum was occupied by mazindol. Meanwhile, the binding potential of 11C-raclopride reduced by 4 &#8211; 6%, but the reduction was not significant, indicating the change in extracellular dopamine levels by mazindol without neuropsyhological tasks was small. The correlation between the occupancy of dopamine transporter and the change in 11C-raclopride binding was not significant, but there seemed a tendency that the occupancy was negatively related to the change in 11C-raclopride binding among subjects in the associative striatum.
Conclusions:
After oral administration of 1.5 mg of mazindol, dopamine transporters were occupied in a small proportion, and the change in extracellular dopamine levels was minimal. Further studies with a larger sample size would be needed to investigate the relationship between the occupancy of dopamine transporter and the change in extracellular dopamine levels by oral administration of mazindol., Brain'13 & BrainPET'13},
 title = {Occupancy of dopamine transporter and&#8232; the effect of dopamine reuptake inhibition&#8232; by mazindol in living human brain},
 year = {2013}
}