In vitro metabolism of indomethacin morpholinylamide (BML-190), an inverse agonist for the peripheral cannabinoid receptor (CB(2)) in rat liver microsomes.
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.
Zhang
Qiang
Q
Department of Chemistry, Xavier University of Louisiana, 1 Drexel Dr, New Orleans, LA 70125, USA.
Ma
Peng
P
Cole
Richard B
RB
Wang
Guangdi
G
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D007213:Indomethacin / Q000031:analogs & derivatives* / Q000378:metabolism; D008862:Microsomes, Liver / Q000378:metabolism*; D009025:Morpholines / Q000378:metabolism*; D051381:Rats; D043885:Receptor, Cannabinoid, CB2 / Q000037:antagonists & inhibitors*; D013056:Spectrophotometry, Ultraviolet; D053719:Tandem Mass Spectrometry
D009025:Morpholines; D043885:Receptor, Cannabinoid, CB2; C471852:indomethacin morpholinylamide; D007213:Indomethacin