1998 Fiscal Year Final Research Report Summary
Neurotransmission in human brains measured by 3D-PET
| Project/Area Number |
08044235
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| Research Category |
Grant-in-Aid for international Scientific Research
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| Allocation Type | Single-year Grants |
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| Section | Joint Research |
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| Research Field |
Neurochemistry/Neuropharmacology
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| Research Institution | Tohoku University |
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Principal Investigator |
YANAI Kazuhiko TOHOKU UNIVERSITY SCHOOL OF MEDICINE,DEPARTMENT OF PHARAMACOLOGY,PROFESSOR, 医学部, 教授 (50192787)
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| Co-Investigator(Kenkyū-buntansha) |
GREEN Jack P. MOUNT SINAI SCHOOL OF MEDICINE,DEPARTMENT OF PHARAMACOLOGY,PROFESSOR, 医学部, 教授
FROST James J. THE JOHNS HOPKINS MEDICAL INSTITUTIONS,DIVISION OF NUCLEAR MEDICINE,PROFESSOR, 医学部, 教授
FUKUI Hiroyuki THE UNIVERSITY OF TOKUSHIMA,FACULTY OF PHARMACEUTICAL SCIENCES,PROFESSOR, 薬学部, 教授 (90112052)
ITOH Masatoshi CYCLOTRON RI CENTER,TOHOKU UNIVERSITY,DEPARTMENT OF PHARAMACOLOGY,PROFESSOR, 教授 (00125501)
WATANABE Takehiko TOHOKU UNIVERSITY SCHOOL OF MEDICINE,DEPARTMENT OF PHARAMACOLOGY,PROFESSOR, 医学部, 教授 (70028356)
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| Project Period (FY) |
1996 – 1998
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| Keywords | Histamine / PET / 3D-PET / H_2^<15>O / activation study / Ligand activation / Human brain / gammaCBF |
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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, was measured in the living human brain. For HA receptors, specific radiotracers for selective labeling of H3 receptors was newly synthesized. 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 ; "C-ligand activation study to measute neurotransmitter release. In this project, we were mainly focus on the PET studies of histaminergic neuron system in the human brain.
Antihistamines are the efficacious drugs to be used for the symptomatic relief of allergic diseases. The safety issue of antihistamines is of central importance because of their widesprea
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d 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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