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A Small-Animal Pharmacokinetic/Pharmacodynamic PET Study of Central Serotonin 1A Receptor Occupancy by a Potential Therapeutic Agent for Overactive Bladder.
https://repo.qst.go.jp/records/47208
https://repo.qst.go.jp/records/472080cff141c-009a-4599-8c00-a7fa9b3150e4
| Item type | 学術雑誌論文 / Journal Article(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2015-08-06 | |||||
| タイトル | ||||||
| タイトル | A Small-Animal Pharmacokinetic/Pharmacodynamic PET Study of Central Serotonin 1A Receptor Occupancy by a Potential Therapeutic Agent for Overactive Bladder. | |||||
| 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 |
Nakatani, Yosuke
× Nakatani, Yosuke× Suzuki, Michiyuki× Tokunaga, Masaki× Maeda, Jun× Sakai, Miyuki× Ishihara, Hiroki× Yoshinaga, Takashi× Takenaka, Osamu× Zhang, Ming-Rong× Suhara, Tetsuya× Higuchi, Makoto× 中谷 陽介× 鈴木 成教× 徳永 正希× 前田 純× 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 | Serotonin 1A (5-HT1A) receptors have been mechanistically implicated in micturition control, and there has been a need for an appropriate biomarker surrogating the potency of a provisional drug acting on this receptor system for developing a new therapeutic approach to overactive bladder (OAB). Here, we analyzed the occupancy of 5-HT1A receptors in living Sprague-Dawley rat brains by a novel candidate drug for OAB, E2110, using positron emission tomography (PET) imaging, and assessed the utility of a receptor occupancy (RO) assay to establish a pharmacodynamic index translatable between animals and humans. The plasma concentrations inducing 50% RO (EC50) estimated by both direct and effect compartment models were in good agreement. Dose-dependent therapeutic effects of E2110 on dysregulated micturition in different rat models of pollakiuria were also consistently explained by achievement of 5-HT1A RO by E2110 in a certain range (≥ 60%). Plasma drug concentrations inducing this RO range and EC50 would accordingly be objective indices in comparing pharmacokinetics-RO relationships between rats and humans. These findings support the utility of PET RO and plasma pharmacokinetic assays with the aid of adequate mathematical models in determining the in vivo characteristics of a drug acting on 5-HT1A receptors and thereby counteracting OAB. | |||||
| 書誌情報 |
PloS one 巻 8, 号 9, p. e75040, 発行日 2013-09 |
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| ISSN | ||||||
| 収録物識別子タイプ | ISSN | |||||
| 収録物識別子 | 1932-6203 | |||||
| PubMed番号 | ||||||
| 識別子タイプ | PMID | |||||
| 関連識別子 | 24086433 | |||||
| DOI | ||||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | 10.1371/journal.pone.0075040 | |||||
