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Possible role of organic cation transporters in the distribution of [11C]sulpiride, a dopamine D2 receptor antagonist
https://repo.qst.go.jp/records/48680
https://repo.qst.go.jp/records/48680895fe9e6-c1da-4467-8898-e8e4b956010a
| Item type | 学術雑誌論文 / Journal Article(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2018-04-08 | |||||
| タイトル | ||||||
| タイトル | Possible role of organic cation transporters in the distribution of [11C]sulpiride, a dopamine D2 receptor antagonist | |||||
| 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 |
Takano, Harumasa
× Takano, Harumasa× Ito, Sumito× Zhang, Xuan× Ito, Hiroshi× Zhang, Ming-Rong× Suzuki, Hiroshi× Maeda, Kazuya× Kusuhara, Hiroyuki× Suhara, Tetsuya× Sugiyama, Yuichi× 高野 晴成× 伊藤 浩× 張 明栄× 須原 哲也 |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | We synthesized [11C]sulpiride as a positron emission tomography (PET) probe for investigating the drug distribution in the human body. [11C]Sulpiride was injected to healthy male subjects in either tracer dose of [11C]sulpiride (ca 222 MBq) or with therapeutic dose of sulpiride (500 mg, po) 3 hours prior to the injection in a crossover fashion. Whole body PET imaging demonstrated that [11C]sulpiride accumulated exceedingly in the bladder, followed by liver, gall bladder and kidney respectively; at 30 minutes after the injection, whereas scarcely in the brain. Oral dose of sulpiride decreased the hepatic accumulation of the radioactivity by 60%. From in vitro experiments, we found that sulpiride is a substrate of hOCT1 (Km 2.6μM), hOCT2 (Km 68μM), hMATE1 (Km 40μM) and hMATE2-K (Km 60μM). Moreover, the uptake of sulpiride by human hepatocytes was diminished by tetraethylammonium, and saturable with Km of 18 μM. Oct1/2 double knockout mice, and wild-type mice received Mate1 inhibitors (pyrimethamine/cimetidine) manifested reduced renal clearance of sulpiride, accompanied with its accumulation in the plasma. In conclusion, we found that sulpiride is a substrate of OCT1, OCT2, MATE1 and MATE2-K; and this suggests that [11C]sulpiride would be useful radiologand to investigate the organic cation transporters in humans. | |||||
| 書誌情報 |
Journal of Pharmaceutical Sciences 巻 106, 号 9, p. 2558-2565, 発行日 2017-05 |
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| ISSN | ||||||
| 収録物識別子タイプ | ISSN | |||||
| 収録物識別子 | 0022-3549 | |||||
| PubMed番号 | ||||||
| 識別子タイプ | PMID | |||||
| 関連識別子 | 28499878 | |||||
| DOI | ||||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | 10.1016/j.xphs.2017.05.006 | |||||
