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Acetylcholinesterase Imaging: Its Use in Therapy Evaluation and Drug Design
https://repo.qst.go.jp/records/44418
https://repo.qst.go.jp/records/4441801d30ae7-e5b1-43bd-9a32-39c16f4ebe0b
| Item type | 学術雑誌論文 / Journal Article(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2006-07-06 | |||||
| タイトル | ||||||
| タイトル | Acetylcholinesterase Imaging: Its Use in Therapy Evaluation and Drug Design | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
| 資源タイプ | journal article | |||||
| アクセス権 | ||||||
| アクセス権 | metadata only access | |||||
| アクセス権URI | http://purl.org/coar/access_right/c_14cb | |||||
| 著者 |
Shinoto, Hitoshi
× Shinoto, Hitoshi× Fukushi, Kiyoshi× Nagatsuka, Shinnichiro× Irie, Toshiaki× 篠遠 仁× 福士 清× 長塚 伸一郎× 入江 俊章 |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Several cholinesterase (ChE) inhibitors have been labeled with carbon-11 for visualizing binding sites on acetylcholinesterase (AChE) by positron emission tomography (PET). Following intravenous injection of 1,2,3,4- tetrahydro-9-[11C]methylaminoacridine or [11C]donepezil, however, the radioactivity distribution does not reflect the regional distribution of AChE in the brain of animals. Probably because these compounds have high non-specific binding and/or other specific binding sites in vivo in the brain. PET studies with [11C]physostigmine and [11C]CP-126,998 in the brain of healthy subjects have shown a radioactivity distribution corresponding to the regional distribution of AChE activity measured in postmortem human brains. These radiotracers may be useful for measuring the occupancy of binding sites on AChE by AChE inhibitors, and for investigating cerebral pharmacokinetics of such therapeutic drugs. \nAn alternative approach to map AChE is the use of acetylcholine analogue substrates. We have developed N-methylpiperidinyl esters labeled with carbon-11 for quantitative measurement of AChE activity. Currently, two N-[11C]methylpiperidine esters. N-[11C]methylpiperidin-4-ylaceta (MP4A) and N-[11C]methylpiperidin-4-yl propionate (MP4P or PMP), have been used for clinical studies of Alzheimer's disease and other neurodegenerative diseases. Both [11C]MP4A-and [11C]MP4P-PET have demonstrated not only the reduction of AChE activity in the cerebral cortex of patients with Alzheimer's disrase (AD) but also the inhibitory effects of donepezil and rivastigmine on AChE activity in the brain of AD patients. AChE imaging should prove useful for therapeutic monitoring of the effects of ChE inhibitors, including determination of the appropriate clinical doses of newly developed compounds, and can thus prompt the development of novel drugs targeting AChE. |
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| 書誌情報 |
Current Pharmaceutical Design 号 10, p. 1505-1517, 発行日 2004 |
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| ISSN | ||||||
| 収録物識別子タイプ | ISSN | |||||
| 収録物識別子 | 1381-6128 | |||||
