| Project/Area Number |
11694234
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
応用薬理学・医療系薬学
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| Research Institution | Tohoku University |
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Principal Investigator |
YANAI Kazuhiko TOHOKU UNIVERSITY SCHOOL OF MEDICINE, PROFESSOR, 大学院・医学系研究科, 教授 (50192787)
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| Co-Investigator(Kenkyū-buntansha) |
TASHIRO Manabu TOHOKU UNIVERSITY SCHOOL OF MEDICINE, RESEARCH ASSOCIATE, 大学院・医学系研究科, 助手 (00333477)
ITOH Masatoshi TOHOKU UNIVERSITY CYCLOTRON AND RADIOISOTOPE CENTER, PROFESSOR, サイクロトロンRIセンター, 教授 (00125501)
IWATA Ren TOHOKU UNIVERSITY CYCLOTRON AND RADIOISOTOPE CENTER, ASSOCIATE PROFESSOR, 大学院・工学研究科, 助教授 (60143038)
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| Project Period (FY) |
1999 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥19,480,000 (Direct Cost: ¥17,800,000、Indirect Cost: ¥1,680,000)
Fiscal Year 2001: ¥7,280,000 (Direct Cost: ¥5,600,000、Indirect Cost: ¥1,680,000)
Fiscal Year 2000: ¥5,600,000 (Direct Cost: ¥5,600,000)
Fiscal Year 1999: ¥6,600,000 (Direct Cost: ¥6,600,000)
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| Keywords | Radiopharmaceuticals / PET / receptor occupancy / cognitive function / cerebral blood flow / ligand-activation study / carbon-11 / fluorine-18 / Carbon-11(^<11>C) / carbon-11(^<11>C) / carbon-11(C^<11>) / fluorine-18(F^<18>) / histamine / 脳賦活試験 / H_2O^<15> / 眠気 / アルツハイマー病 |
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| Research Abstract |
Positron emission tomography (PET) is a unique method to examine brain chemistry non-invasively in humans. Using PET techniques, specific neurochemical systems, such as dopaminergic and histaminergic neuronal systems, were measured in the living human brain. Specific ^<11>C- or ^<18>F-labelled radiotracers for selective labeling of several receptors were newly synthesized by new synthetic methods. We also developed several new methods of imaging in the human brain using 3-demensional PET system. Our developed PET methods for human neuropharmacology are as follows : Non-invasive measurement of receptor binding parameters ; cerebral activation study with H_2^<15>O and 3D-PET ; ^<11>C-ligand activation study to measure neurotransmitter release. As for pharmacological applications, we used PET techniques for evaluating sedative properties of antihistamines. Antihistamines are the efficacious drugs to be used for the symptomatic relief of allergic diseases. The safety issue of antihistamine
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s is of central importance because of their widespread use in current medical practice. PET was used to better understand the pharmacological effects of antihistamines on the central nervous system. The H1 receptor occupancy was examined in young male volunteers with [^<11>C]-doxepin (a potent H1 antagonist) after the oral or intravenous administration of antihistamines. In other studies, the cognitive performance was also measured tachistoscopically before and after taking antihistamines. The H1 receptor occupancy in the human frontal cortex caused by antihistamines is significantly correlated with the reported values of incidence of sleepiness in clinical trials, and the occupancy is well proportional to the impaired cognitive performance. To understand the brain mechanism of antihistamine-induced "sleepiness and impaired cognition", the regional cerebral blood flow (rCBF) during the task was measured using 3D-PET and H_2^<15>O before and after administration of d-chlorpheniramine. After its administration, the rCBF was significantly decreased on the bilateral middle temporal gyrus, midbrain and anterior cingulate. These findings suggest that H1 receptor blockade would be affected on the activity of the attention and cognitive system in the brain. Less
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