@misc{oai:repo.qst.go.jp:00067600,
 author = {Saito, Keita and Takeshita, Keizo and Anzai, Kazunori and Ozawa, Toshihiko and 齋藤 圭太 and 竹下 啓蔵 and 安西 和紀 and 小澤 俊彦},
 month = {Apr},
 note = {Hydroxylamines should be useful probes for in vivo ESR detection of reactive oxygen species (ROS), because they react with superoxide and peroxynitrite to generate nitroxyl radicals giving ESR signals.  Acyl-protected hydroxylamine probe, 1-acetoxy-3-carbamoyl-2,2,5,5-tetramethylpyrrolidine (ACP), has been designed to be hydrolyzed to generate hydroxylamine in living body (Itoh et al. 2000, Chem. Lett., Yordanov et al. 2002, J. Med. Chem.).  However, the pharmacokinetics of ACP in animal bodies is not understood.  Therefore, we investigated the distribution of ACP, its hydroxylamine-form and its nitroxyl radical-form (carbamoyl-PROXYL) in mice after injection of ACP.  ACP (140 mM, 200mL) was injected intravenously to male ddY mice (4 weeks old).  Organs were removed 3, 10 and 30 min after the injection.  Concentration of ACP and carbamoyl-PROXYL in the organ homogenates was measured with HPLC and X-band ESR spectroscopy, respectively.  Concentration of hydroxylamine-form was estimated by measurement with X-band ESR after one electron oxidation.  ACP was distributed in lung, stomach, heart, spleen, brain, and blood 3 min after intravenous injection.  The content in brain was relatively low.  The hydroxylamine-form was observed at high content in liver and kidney, whereas the content of ACP was very low in the both organs.  Content of hydroxylamine-form decreased with time in liver and kidney, while it increased in other organs.  The hydroxylamine-form was equally distributed in the organs except for brain 30 min after injection.  Content of carbamoyl-PROXYL was still low at this time.  Hydrolysis of ACP occurred remarkably in homogenates of liver and kidney.  These observations indicate that ACP is hydrolyzed mainly in liver and kidney to hydroxylamine-form which is then distributed to other organs.  These basic data about the pharmacokinetics of ACP are useful for in vivo ESR measurements of reactive oxygen species., The 10th International workshop on Bio-Medical ESR Spectroscopy and Imaging},
 title = {Pharmacokinetics of Acyl-Protected Hydrolyalamine Probe, 1-Aceoxy-3-carbamoyl-2,2,5,5-tetramethylpyrrodine, for In Vivo Application of the Probe},
 year = {2003}
}