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The research of the cerebral serotonin transporter and Receptor in affective disorder with positron emission tomography

Research Project

Project/Area Number 09470212
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Psychiatric science
Research InstitutionNational Institute of Radiological Sciences

Principal Investigator

SUHARA Tetsuya  National Institute of Radiological Sciences Division of Advanced Technology for Medical Imaging, Senior Researcher, 高度診断機能研究ステーション, 主任研究官 (90216490)

Co-Investigator(Kenkyū-buntansha) HARADAHIRA Terushi  National Institute of Radiological Sciences Division of Advanced Technology for Medical Imaging, Senior Researcher, 高度診断機能研究ステーション, 主任研究官 (50181029)
OKUBO Yoshiro  Tokyo Medical and Dental University Faculty of Medicine, School of Allied Health Sciences Department of Clinical Physiology, Professor, 医学部・保健衛生学科機能検査学, 教授 (20213663)
SUZUKI Kazutoshi  National Institute of Radiological Sciences Division of Advanced Technology for Medical Imaging, 高度診断機能研究ステーション・第一ユニット, ユニットリーダー (90162932)
NAKAYAMA Kazuhiko  The Jikei University School of Medicine Department of Psychiatry, Associate Professor, 精神医学講座, 助教授 (70155878)
MURAYAMA Hideo  National Institute of Radiological Sciences Division of Advanced Technology for Medical Imaging, Senior Researcher, 高度診断機能研究ステーション, 主任研究官 (50166310)
Project Period (FY) 1997 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥15,300,000 (Direct Cost: ¥15,300,000)
Fiscal Year 1999: ¥5,100,000 (Direct Cost: ¥5,100,000)
Fiscal Year 1998: ¥4,500,000 (Direct Cost: ¥4,500,000)
Fiscal Year 1997: ¥5,700,000 (Direct Cost: ¥5,700,000)
KeywordsPET / Serotonin Transporter / Antidepressant / Lung / Occupancy / [11C] McN5652-X / [11C] Cyanoimipramine / Intrinsicserotonin / 内在性セロノニン / 5-HT1A受容体,5-HT7受容体 / うつ薬 / 〔11C〕WAY100635 / 5-HTIA受容体 / 代謝 / [11C]McN5652-X / [11C]WAY100635 / SSRI / 抗うつ薬 / 体内動態 / 薬物相互作用
Research Abstract

1. Research on antidepressants in pharmacokinetic drug interactions
We have investigated the role of lung in pharmacokinetic drug interactions between tricyclic antidepressants and SSRIs using [ィイD111ィエD1C] cyanoimipramine. A large proportion of the injected [ィイD111ィエD1C] cyanoimipramine (70-80%) was accumulated in the lung. Fifty mg of clomipramine, antidepressant with high affinity for the serotonin transporter, decreased the lung uptake of [ィイD111ィエD1C] cyanoimipramine in approximately 40%. Whole-brain uptake was low in control state but increased significantly after clomipramine administration. The lungs may function as a reservoir for antidepressants with high affinity to the serotonin transporter. The accumulated antidepressants may be displaced by other antidepressants, and this displacement would substantially increase plasma concentrations and thus cause toxic effects.
2. Measurement of serotonin transporter occupancy with antidepressants
We demonstrated the occupancy of serotoni … More n transporters using [ィイD111ィエD1C] McN5652-X. We measured the changes of the specific binding in thalamus using the cerebellum as a non-specific binding site. Approximately 50-70% of serotonin transporter were occupied by clinical dose of clomipramine. Using inactive stereoisomer [ィイD111ィエD1C] (-) McN5652, non-specific binding was reevaluated and it was larger than previous evaluation. Calculated occupancy using [ィイD111ィエD1C] (-) McN5652 as non specific binding was 90 % by 50 mg of clomipramine and 95%, 75% of occupancy was calculated after administration of 50 mg, 25 mg fluboxamine
3. Development of a new method to measure the endogenous serotonin
The bindings of endogenous serotonin were analyzed by using a 5-HT1A receptor agonist, [ィイD111ィエD1C] WAY100635 after administration of fenflramin or reserpine. Endogenous serotonin had no significant effect on [ィイD111ィエD1C] IWAY100635 binding in vivo.
4. Serotonin transporters in mood disorders
The binding potentials of [ィイD111ィエD1C] McN5652-X were 0.89±0.17 (mean±S.D.) in thalamus, 0.93±0.26 in left basal ganglia and 0.87±0.18 in right basal ganglia in patients with mood disorders. In the control group, the binding potentials were 0.77±0.24 in thalamus, 0.88±0.37 in left basal ganglia and 0.92±0.30 in right basal ganglia. There was no significant difference of binding potentials between patients and controls. However, there was a positive correlation between the binding potentials of right basal ganglia and Hamilton depression scores (F=7.90, P=0.20). Less

Report

(4 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • 1997 Annual Research Report
  • Research Products

    (39 results)

All Other

All Publications (39 results)

  • [Publications] Suhara T.,Sudo Y.,Yoshida K,.Okubo Y.,Fukuda H.,Obata T.,Yoshikawa K.,Suzuki K.,Sasaki Y.: "Lung as a reservoir for antidepressants in pharmacokinetic drug interactions"Lancet. 351. 332-335 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Sudo Y.,Suhara T., Honda Y.,Suzuki K.,Nakajima T.,Okubo Y.,Nakashima Y.,Yoshikawa K.,Okauchi T.,Sasaki Y..Matsushita M.: "Muscarinic Acetylcholinergic Receptors of Human Narcolepsy : A Positron Emission Tomography Study"Neurology. 51. 1297-1302 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Sudo Y.,Suhara T.,Suzuki K.,Okubo Y.,Yoshikawa K.,Uchida S.,Sassa T.,Okauchi T.,Sasaki Y.,Matsushita M.: "Muscarinic receptor occupancy by biperiden in living human brain"Life Sci. 64. 99-104 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Suhara T.,Sudo Y.,Okauchi T.,Maeda J.,Kawabe K.,Suzuki K.,Okubo Y.,Nakashima Y.,Ito H.,Tanada S..Halldin C.,Farde L.: "Extrastriatal dopamine D2 receptor density and affinity in the human brain measured by 3D PET"Int J Neuropsychopharmacol. 2. 73-82 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Suhara T: "Visualizing the site of drug action in living human brain"Proceedings of the 7th international symposium on advanced nuclear energy research. Recent progress in accelerator beam application. 97-003. 84-85 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Sassa T.,Girard F.,Suhara T.,Sudo Y.,Koga M.,Obata T.,Okubo Y.,Toru M., Ikehira H.,Yoshida K.: "Direct 2D-spectroscopic imaging of lithium in patients"p209S, Supplement to Biological Psychiatry, A journal of psycchiatic Research. Volume 42. (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Suhara T.,Sudo Y.,Okubo Y.,Obata T.,Yoshida K.,Yoshikawa K.,Suzuki K.: "Role of pulmonary binding site on pharmacokinetics of antidepressants measured by PET"p293S, Supplement to Biological Psychiatry, A journal of psycchiatic Research. Volume 42. (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Suhara T: "The application of radioisotope to the mental disorders research and Psychopharmacology Psychopharmacology"Proceedings of The 23rd Japan Conference on Radiation and Radioisotopes. A13. 2-11 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Suhara T: "PET in neuropsychiatric drug pharmacokinetics"Jap J Pharmacol. 79(Suppl I). 27 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Suhara T: "Functional imaging of emotion and motivation"Neuroscience Res. Suppl 23. S19 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Suhara T., Sudo Y., Yoshida K., Okubo Y., Fukuda H., Obata T., Yashikawa K., Suzuki K., Sasaki Y.: "Lung as a reservoir for antidepressants in pharmacokinetic drug interactions"Lancet. 351. 332-335 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Sudo Y., Suhara T., Honda Y., Suzuki K., Nakajima T., Okubo Y., Nakashima Y., Yoshikawa K., Okauchi T., Sasaki Y., Matsushita M.: "Muscarinic Acetyicholinergic Receptors of Human Narcolepsy"A Positron Emission Tomography Study Neurology. 51. 1297-1302 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Sudo Y., Suhara T., Suzuki K., Okubo Y., Yoshikawa K., Uchida S., Sassa T., Okauchi T., Sasaki Y., Matsushita M.: "Muscarinic receptor occupancy by biperiden in living human brain"Life Sci.. 64. PL 99-104 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Suhara T., Sudo Y., Okauchi T., Maeda J., Kawabe K., Suzuki K., Okubo Y., Nakashima Y., Ito H., Tanada S., Halldin C., Farde L: "Extrastriatal dopamine D2 receptor density and affinity in the human brain measured by 3D PET"Int J Neuropsychopharmacol. 2. 73-82 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Suhara T: "Visualizing the site of drug action in living human brain."Proceeedings of the 7th international symposium on advanced nuclear energy research.Recent progress in accelerator beam application. 97-003. 84-85 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Sassa T., Girard F., Suhara T., Sudo Y., Koga M., Obata T., Okubo Y., Toru M., Ikehira H., Yoshida K.: "Direct 2D-spectroscopic imaging of lithium in patients p209S, Supplement to Biological Psychiatry, A journal of psycchiatic Research"p209S, Supplement to Biological Psychiatry, A journal of psycchiatic Research. Volume 42. (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Suhara T., Sudo Y., Okubo Y. Obata T., Yoshida K. Yoshikawa K., Suzuki K.: "Role of pulmonary binding site on pharmacokinetics of antidepressants measured by PET"p239S, Supplement to Biological Psychiatry, A journal of psycchiatic Research. Volume 42. (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Suhara, T: "The application of radioisotope to the mental disorders research and Psychopharmacology Psychopharmacology"Proceedings of The 23rd Japan Conference on Radiation and Radioisotopes. A13. 2-11 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Suhara T: "PET in neuropsychiatric drug pharmacokinetics"Jap J Pharmacol. 79(Suppl.I). 27 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Suhara T.: "Functional imaging of emotion and motivation"Neuroscience Res Suppl. 23. S19 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Suhara T.: "Functional imaging of emotion motivation"Neuroscience Research Suppl. 23. S19 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] T.Suhara,Y.Okauchi,Y.sudo et al.: "Extrastriatal dopamine D2 receptor density and affinity in the human brain measured by 3D PET"International Journal Nmeuropsychopharmacology. 2. 73-82 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Y.Okubo,H.Olsson,H.Ito,T.Suhara et al.: "Computerized atlas of extrastriatal De dopamine receptors in the living human brain : ....."Neuro,Image. 10. 666-674 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Y.Akine,T.Obata,Y.Suhara,S.Umeda et al.: "Neural correlates of fal recognition : a functional MRI study"NeuroImage. 9(6). S984 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] T.Suhara: "PET in neuropsyciatric drug pharmacokinetics"Japan Journal of Pharmacology. 79(Suppl I). 27 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 山本正浩、須原哲也、大久保善朗: "人格と脳機能画像"脳の科学. 21. 1069-1074 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 染谷康宏、秀野武彦、須原哲也: "第18章精神科診療における画像診断 プライマリーケアのための心の病診療プラクティス"清水信・中山和彦編 永井書店、東京. 193-202

    • Related Report
      1999 Annual Research Report
  • [Publications] 安野史彦、須原哲也: "臨床精神医学講座 第10巻精神科臨床における画像診断"中山書店,東京,編集責任 松田博史、倉知正佳(印刷中).

    • Related Report
      1999 Annual Research Report
  • [Publications] Sudo Y.,Suhara T.Suzuki K.,et al.: "Muscarinic receptor occupancy by biperiden in living human brain." Life Science. 64. PL99-104 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Suhara,T: "The application of radioisotope to the mental disorders research and Psychopharmacology." Proceedings of The 23rd Japan Conference on Radiation and Radioisotopes. A13. 1-11 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 須原哲也: "ライフサイエンス、東京" 村崎光邦・上島国利編,CNS Symposium 1997, 8 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 須藤康彦、須原哲也、岡内隆: "脳の科学 増刊号 脳機能のイメージング -基礎から臨床まで-" PETによるモノアミントランスポーターのイメージング, 5 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Suhara T.,et al.: "Lung as a reservoir for antidepressants in pharmacokinetic drug interactions." Lancet. 351. 332-335 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Girard F.,Suhara T.,et al.: "Direct two-dimensional spectroscopic imaging of lithium." Elsevier Science,Amsterdam. 225-232 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Suhara T: "Visualizing the site of drug action in living human brain." Recent progress in accelerator beam application. 97-003. 84-85 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Sassa T.,Girard F.,Suhara T.,et al.: "Direct 2D-spectroscopic imaging of lithium in patients" A journal of psycchiatic Research. 42. 209S (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Suhara T.,et al.: "Role of pulmonary binding site on pharmacokinetics of antidepressants measured by PET" A journal of psycchiatic Research. 42. 239S (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 須藤康彦,須原哲也: "クリニカルPET-臨床応用のためのガイドブック-" 鳥塚莞爾編,先端医療技術研究所, 7 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 須原哲也: "脳シグナルカスケードと精神疾患" 樋口輝彦・三国雅彦,学会出版センター, 26 (1997)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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