| 論文名 |
Elimination pathways of cyclosarin (GF) mediated by β-cyclodextrin in vitro: pharmacokinetic and toxicokinetic aspects. |
| 著者 |
Andreas Kranawetvogl
Jan Sch?ler
Susanne M?ller
Horst Thiermann
Franz Worek
Georg Reiter
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| キーワード |
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| 出版年月 |
1970年1月 |
| 発表先 |
Toxicol Lett. 2013 Oct 24;222(2):164-70. |
| WEBサイト |
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| 論文概要（和文） |
in vitroでのβ-シクロデキストリンによって媒介されるシクロサリン（GF）の排除経路：薬物動態および毒性動態の側面。 |
| 論文概要（英文） |
Cyclodextrins (CD) are promising small molecular scavengers showing favourable degradation of extremely toxic organophosphorus compounds (OP) such as tabun (GA), soman (GD) or cyclosarin (GF). For β-CD derivatives as potential OP antidotes with low intrinsic toxicity it is of great interest to completely understand the modes of interaction of both compounds in terms of OP detoxification. The mechanisms of CD action are not completely understood which prompted us to investigate the interactions of GF and β-cyclodextrin (β-CD) as model compounds. Using positive electrospray ionization mass spectrometry (ESI/MS), the formation of covalent conjugates of β-CD with O-cyclohexylmethylphosphonate (CHMP) residue was detected for the first time and was examined in vitro. With a newly developed LC-MS method the formation of O-cyclohexylmethylphosphonic acid (CHMPA) (i.e. GF hydrolysis) and covalent CHMP-β-CD conjugates was analyzed. Compared to water, tris(hydroxymethyl)aminomethane (TRIS) reduced the formation of covalent conjugates but amplified formation of CHMPA. Depending on experimental conditions the degradation of GF by β-CD may be preferably catalytic or stoichiometric. For illustrating different possible reaction pathways a scheme was established that could support the idea of β-CD acting as an artificial enzyme. These results provide an important insight into the β-CD mediated detoxification pathways of GF. |
