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Quantification of central substance P receptor occupancy by aprepitant using small animal positron emission tomography.
https://repo.qst.go.jp/records/47071
https://repo.qst.go.jp/records/47071916828d5-c60c-444f-876d-f84c5cb3907a
| Item type | 学術雑誌論文 / Journal Article(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2015-03-25 | |||||
| タイトル | ||||||
| タイトル | Quantification of central substance P receptor occupancy by aprepitant using small animal positron emission tomography. | |||||
| 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 |
Endo, Tadashi
× Endo, Tadashi× Saijo, Takeaki× Haneda, Eisuke× Maeda, Jun× Tokunaga, Masaki× Zhang, Ming-Rong× Kannami, Ayako× Asai, Hidetoshi× Suzuki, Masayuki× Suhara, Tetsuya× Higuchi, Makoto× 遠藤 忠× 西條 武明× 前田 純× 徳永 正希× 張 明栄× 須原 哲也× 樋口 真人 |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Central substance P receptors, termed NK-1 receptors, have been considered as therapeutic targets in the development of drugs against diverse conditions including emesis, overactive bladder and depression. Here, we applied small animal positron emission tomography (PET) and a radioligand for NK-1 receptors, [18F]FE-SPA-RQ, for measuring occupancies of these receptors by a selective antagonist, aprepitant, in order to examined the validity of this in vivo imaging system for preclinical characterization of candidate agents acting on NK-1 receptors, and as a tool for predicting optimal doses in humans. PET in gerbils depicted high uptake in the striatum and dose-dependent displacement with increasing dose of aprepitant. Occupancies increased as a function of aprepitant plasma concentrations according to a one-site competition model, in good agreement with reported occupancy-concentration relationships in clinical studies after correction for species differences in plasma protein-unbound aprepitant fractions. These occupancy data were further supported by ex vivo autoradiography of brain samples from aprepitant-treated gerbils. In a pilot study of a marmoset, we obtained more accurate determinations of NK-1 receptor occupancy, less affected by spillover of signals from extracranial tissues than in gerbil experiments. These findings support the utility of small animals and quantitative PET in the development of drugs targeting NK-1 receptors. | |||||
| 書誌情報 |
The international journal of neuropsychopharmacology / official scientific journal of the Collegium Internationale Neuropsychopharmacologicum (CINP) 巻 18, 号 2, p. 1-10, 発行日 2014-10 |
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| 出版者 | ||||||
| 出版者 | Cambridge University Press | |||||
| ISSN | ||||||
| 収録物識別子タイプ | ISSN | |||||
| 収録物識別子 | 1461-1457 | |||||
| PubMed番号 | ||||||
| 識別子タイプ | PMID | |||||
| 関連識別子 | 25609595 | |||||
| DOI | ||||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | 10.1093/ijnp/pyu030 | |||||
