一种取代氨基乙酰氨基二苯甲酮在大鼠体内的代谢及环化生成相应苯二氮䓬的过程。

The metabolism of a substituted aminoacetamido-benzophenone and cyclization to the corresponding benzodiazepine in the rat in vivo.

Rising P A, Illing H P, Johnson P, Yeomans M A

Xenobiotica. 1977 Jul;7(7):425-37. doi: 10.3109/00498257709035802.

Abstract

2-(5-Cyano-N-methyl-3,5-dimethyl-3-aza-pentanamido)-5-nitrobenzophenone, administered orally to the rat, is well absorbed and extensively metabolized with only minimal quantities of parent compound detected in plasma, bile or urine. 2. Urinary t.l.c. metabolite profiles after oral administration of a substituted aminoacetamidobenzophenone, [14C]C 72 0045, and [14C]nimetazepam were qualitatively similar but differed quantitatively. 3. Analysis by t.l.c. of plasma extracts obtained after oral administration of [14C]C 72 0045 demonstrated that nimetazepam and nitrazepam accounted for 20% of the plasma total radioactivity. Nimetazepam and nitrazepam had a combined concentration up to 22 times greater than the concentration of C 72 0045. 4. The presence of nimetazepam in plasma after oral administration of C 72 0045 was confirmed by mass spectrometry. 5. In the liver, [14C]C 72 0045 was rapidly metabolized to polar metabolites. In the same rats, the major brain metabolites were nimetazepam and nitrazepam. 6. It is concluded that [14C]C 72 0045 undergoes metabolic cyclization in the rat to form nimetazepam, which is further metabolized to form nitrazepam.

摘要

2-(5-氰基-N-甲基-3,5-二甲基-3-氮杂戊酰胺基)-5-硝基二苯甲酮经口服给予大鼠后，吸收良好且广泛代谢，在血浆、胆汁或尿液中仅检测到极少量的母体化合物。2. 口服一种取代氨基乙酰氨基二苯甲酮[14C]C 72 0045和[14C]硝西泮后尿薄层色谱代谢物谱在定性上相似，但在定量上有所不同。3. 对口服[14C]C 72 0045后获得的血浆提取物进行薄层色谱分析表明，硝甲西泮和硝西泮占血浆总放射性的20%。硝甲西泮和硝西泮的合并浓度比C 72 0045的浓度高22倍。4. 口服C 72 0045后血浆中硝甲西泮的存在通过质谱法得到证实。5. 在肝脏中，[14C]C 72 0045迅速代谢为极性代谢物。在同一些大鼠中，主要的脑代谢物是硝甲西泮和硝西泮。6. 得出结论，[14C]C 72 0045在大鼠体内经历代谢环化形成硝甲西泮，硝甲西泮进一步代谢形成硝西泮。