Department of Chemistry, Xavier University of Louisiana, 1 Drexel Dr, New Orleans, LA 70125, USA.
Eur J Pharm Sci. 2010 Sep 11;41(1):163-72. doi: 10.1016/j.ejps.2010.06.004. Epub 2010 Jun 11.
The in vitro metabolism of an inverse agonist of the peripheral cannabinoid receptor (CB(2)), indomethacin morpholinylamide (BML-190), has been characterized using rat liver microsomal incubation. BML-190 was found to yield at least 15 metabolic products as identified by HPLC-MS/MS analysis. Four major phase one metabolic pathways either individually, or in combination, were proposed to account for the identified metabolic products: (1) loss of the p-chlorobenzyl group, (2) hydroxylation on the indole or on the morpholine ring, (3) morpholinyl ring opening, and (4) demethylation of the methoxyl group on the indole ring.
采用大鼠肝微粒体孵育方法对一种外周大麻素受体(CB2)反向激动剂(吲哚美辛吗啉酰胺,BML-190)的体外代谢进行了研究。通过 HPLC-MS/MS 分析,发现 BML-190 至少生成了 15 种代谢产物。提出了至少有 4 种主要的一期代谢途径,单独或组合在一起,可以解释所鉴定的代谢产物:(1)失去对氯苄基,(2)吲哚或吗啉环的羟化,(3)吗啉环开裂,(4)吲哚环上甲氧基的去甲基化。