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Utility of small-animal positron emission tomographic imaging of rats for preclinical development of drugs acting on serotonin transporter
https://repo.qst.go.jp/records/45828
https://repo.qst.go.jp/records/458287207d3d3-b0ca-4147-9817-ab36b5ed4ce8
Item type | 学術雑誌論文 / Journal Article(1) | |||||
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公開日 | 2010-06-17 | |||||
タイトル | ||||||
タイトル | Utility of small-animal positron emission tomographic imaging of rats for preclinical development of drugs acting on serotonin transporter | |||||
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 |
Saijo, Takeaki
× Saijo, Takeaki× Maeda, Jun× Okauchi, Takashi× Suzuki, Kazutoshi× Higuchi, Makoto× Suhara, Tetsuya× et.al× 西條 武明× 前田 純× 岡内 隆× 鈴木 和年× 樋口 真人× 須原 哲也 |
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抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | Visualization of neurotransmission components in living small animals using positron emission tomography(PET) has the potential of contributing to the preclinical development of neuroactive drugs, although it is yet to be examined whether quantitative animal PET data on candidate compounds can be extrapolated to humans. Here, we investigated the comparability of the occupancies of serotonin transporter (5-HTT) by therapeutic agents in rat PET studies with our predetermined data from ex- vivo animal experiments and clinical PET scans. Rats were treated with varying doses of fluvoxamine and a newly developed compound, (2S)-1-[4-(3,4-dichlorophenyl) piperidin-1-yl]-3-[2-(5-methyl-1,3,4-oxadiazol-2-yl)-benzo[b]furan-4-yloxy]propan-2-ol monohydrochloride (Wf-516), and underwent PET scans with [11C]3-amino-4-(2-dimethylaminomethyl-phenylsulfanyl)-benzonitrile ([11C]DASB), a selective radioligand for in-vivo quantification of 5-HTT. PET images indicated a reduction of [11C]DASB binding to 5-HTT as a function of the doses and/or plasma concentrations of fluvoxamine and Wf-516. The doses of these drugs at half-maximal effect (15.2 mg/kg and 3.1 mg/kg, respectively), determined that using binding potentials for [11C]DASB, were comparable to those estimated by our previous ex-vivo measurements in rats (4.5 mg/kg and 1.1 mg/kg, respectively), as there was only a 3-fold difference between these results. Moreover, the plasma concentration of fluvoxamine needed for 50% occupancy of central 5-HTT (6.1 ng/ml) was almost equivalent to the value determined in human PET studies (4.6 ng/ml). These findings support the view that the conjunctive use of small-animal PET and [11C]DASB facilitates a quantitative comparison of indevelopment drugs targeting 5-HTT with established inhibitors and a predictive estimation of their plasma concentrations exerting therapeutic effects in humans. | |||||
書誌情報 |
The International Journal of Neuropsychopharmacology 巻 12, 号 8, p. 1021-1032, 発行日 2009-09 |
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ISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 1461-1457 |