Bakri A, Beijersbergen van Henegouwen G M, De Vries H
Center for Bio-Pharmaceutical Sciences, State University of Leiden, the Netherlands.
Pharm Weekbl Sci. 1988 Jun 17;10(3):122-9. doi: 10.1007/BF01959296.
The extent to which diazepam, diazepam-N4-oxide and N4-desoxychlordiazepoxide irreversibly bind to plasma protein upon UV irradiation was determined. Comparison with the results for chlordiazepoxide leads to the conclusion that the N4-oxide function is essential for the occurrence of irreversible binding in vitro. Investigation of the photopharmacology of diazepam in the rat gave results similar to those for N4-desoxychlordiazepoxide: in contrast with what already had been found for chlordiazepoxide no difference was observed between the pharmacology of diazepam in UV-A irradiated rats and those kept in the dark. Both in vitro and in vivo data expand the hypothesis to other 7-chloro-1,4-benzodiazepines, according to which the presence of an N4-oxide group is a prerequisite for the occurrence of phototoxicity and that an oxaziridine is the toxic intermediate.
测定了地西泮、地西泮 - N4 - 氧化物和N4 - 去氧氯氮卓在紫外线照射下与血浆蛋白不可逆结合的程度。与氯氮卓的结果进行比较得出结论，N4 - 氧化物官能团对于体外不可逆结合的发生至关重要。对大鼠体内地西泮的光药理学研究结果与N4 - 去氧氯氮卓相似：与氯氮卓已有的研究结果相反，在紫外线A照射的大鼠和处于黑暗中的大鼠体内，地西泮的药理学没有差异。体外和体内数据均将该假说扩展到其他7 - 氯 - 1,4 - 苯二氮䓬类药物，根据该假说，N4 - 氧化物基团的存在是光毒性发生的先决条件，且恶唑烷是有毒中间体。
