IN-VIVO PHARMACOKINETICS OF NITROXIDES IN MICE
IN-VIVO PHARMACOKINETICS OF NITROXIDES IN MICE
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DOI：
10.1006/bbrc.1994.1806
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发表时间：
1994-06-15
影响因子：
3.1
通讯作者：
LAI, CS
中科院分区：
文献类型：
--
作者：
KOMAROV, AM;JOSEPH, J;LAI, CS
用电子顺磁共振（EPR）谱仪研究了20种不同氮氧化合物在小鼠体内的还原动力学，该谱仪配有S波段环隙谐振器，工作频率为3.5 GHz。共振器的直径（4 mm）与小鼠尾尖非常匹配，因此可以直接检测血液循环中的体内自由基。静脉注射后，随时间跟踪小鼠尾部循环中的氮氧信号;未使用麻醉剂。不同官能团的吡咯烷氮氧自由基（五元环）的t（1/2）值为：= O > COO- > OH > CONH 2，接近CH_2NH_2> NH_2。六元环哌啶氮氧化合物的变化趋势为：COO- > CH_2NH_2> OH，近似NH_2> CONH_2> = O。最引人注目的观察结果是，虽然羰基吡咯烷的t（1/2）值是最长的所有氮氧化物测试的这一性质，羰基哌啶是最短的。比较了六对具有相同官能团的吡咯烷氮氧自由基和哌啶氮氧自由基的体内衰减动力学，发现前者的t（1/2）值比后者长2 ~ 28倍。由此得出的结论是，与哌啶氮氧化物相比，吡咯烷氮氧化物对体内细胞代谢的抵抗力更强。(C)学术出版社
The in vivo reduction kinetics of twenty different nitroxide compounds in mice has been investigated by using an electron paramagnetic resonance (EPR) spectrometer, equipped with an S-band loop-gap resonator, operating at 3.5 GHz. The diameter of the resonator (4 mm) fits well the tip of the mouse tail, thus allowing the direct detection of in vivo free radicals in the blood circulation. After intravenous injection, the nitroxide signal in the circulation of the mouse tail was followed with time; no anesthetic agent was used. For the pyrrolidine nitroxides (five-member rings) with different functional groups, the t(1/2) values followed the order: = O > COO- > OH > CONH2 approximate to CH2NH2 > NH2. A different trend was obtained for the piperidine nitroxides (six-member rings): COO- > CH2NH2 > OH approximate to NH2 > CONH2 > = O. The most striking observation was that while the t(1/2) value of the carbonyl pyrrolidine is the longest among all the nitroxides tested for this property, that of the carbonyl piperidine is the shortest. Comparison of the in vivo decay kinetics of six pairs of pyrrolidine nitroxides and piperidine nitroxides with same functional groups showed that the t(1/2) values of the former are 2 to 28 times longer than the latter. It is concluded here that the pyrrolidine nitroxides are more resistant to cellular metabolism in vivo when compared to the piperidine nitroxides. (C) Academic Press, Inc.