title: Metabolism of a new neuroprotective agent for ischemia-reperfusion damage, KR-31543 in the rat using liquid chromatography/electrospray mass spectrometry.
abstract: KR-31543, (2S,3R,4S)-6-amino-4-[N-(4-chlorophenyl)-N-(2-methyl-2H-tetrazol-5-ylmethyl)amino]-3,4-dihydro-2-dimethoxymethyl-3-hydroxy-2-methyl-2H-1-benzopyran is a new neuroprotective agent for ischemia-reperfusion damage. The in vitro and in vivo metabolism of KR-31543 in rats has been studied by LC-electrospray mass spectrometry. Rat liver microsomal incubation of KR-31543 in the presence of NADPH resulted in the formation of a metabolite M1. M1 was identified as N-(4-chlorophenyl)-N-(2-methyl-2H-tetrazol-5-ylmethyl)amine on the basis of LC-MS/MS analysis with the synthesized authentic standard. Rat CYP3A1 and 3A2 are the major CYP isozymes involved in the formation of M1.
authors.affiliation: Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, Canada.
authors.forename: John
authors.initials: J
authors.lastname: Kim
authors.forename: Hye Young
authors.initials: HY
authors.lastname: Ji
authors.forename: Seung-Seok
authors.initials: SS
authors.lastname: Lee
authors.forename: Sung-Eun
authors.initials: SE
authors.lastname: Yoo
authors.forename: Sun Ok
authors.initials: SO
authors.lastname: Kim
authors.forename: Dong Ha
authors.initials: DH
authors.lastname: Lee
authors.forename: Hong
authors.initials: H
authors.lastname: Lim
authors.forename: Hye Suk
authors.initials: HS
authors.lastname: Lee
mesh_terms: D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases; D001578:Benzopyrans / Q000737:chemistry / Q000378:metabolism* / Q000627:therapeutic use; D002853:Chromatography, Liquid / Q000379:methods; D051544:Cytochrome P-450 CYP3A; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000737:chemistry / Q000378:metabolism* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D013777:Tetrazoles / Q000737:chemistry / Q000378:metabolism* / Q000627:therapeutic use
chemical_list: D001578:Benzopyrans; C473251:KR-31543; D018696:Neuroprotective Agents; D013777:Tetrazoles; D001189:Aryl Hydrocarbon Hydroxylases; C465138:Cyp3a23-3a1 protein, rat; D051544:Cytochrome P-450 CYP3A