@article{oai:repo.qst.go.jp:00047208,
 author = {Nakatani, Yosuke and Suzuki, Michiyuki and Tokunaga, Masaki and Maeda, Jun and Sakai, Miyuki and Ishihara, Hiroki and Yoshinaga, Takashi and Takenaka, Osamu and Zhang, Ming-Rong and Suhara, Tetsuya and Higuchi, Makoto and 中谷 陽介 and 鈴木 成教 and 徳永 正希 and 前田 純 and 張 明栄 and 須原 哲也 and 樋口 真人},
 issue = {9},
 journal = {PloS one},
 month = {Sep},
 note = {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.},
 title = {A Small-Animal Pharmacokinetic/Pharmacodynamic PET Study of Central Serotonin 1A Receptor Occupancy by a Potential Therapeutic Agent for Overactive Bladder.},
 volume = {8},
 year = {2013}
}