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: John Kim, Hye Young Ji, Seung-Seok Lee, Sung-Eun Yoo, Sun Ok Kim, Dong Ha Lee, Hong Lim, Hye Suk Lee
• Journal: Archives of pharmacal research (Arch Pharm Res) Vol. 25 Issue 5 Pg. 664-8 (Oct 2002) ISSN: 0253-6269 [Print] Korea (South)
• PMID: 12433202 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Benzopyrans
• KR-31543
• Neuroprotective Agents
• Tetrazoles
• Aryl Hydrocarbon Hydroxylases
• Cyp3a23-3a1 protein, rat
• Cytochrome P-450 CYP3A

Topics

• Animals
• Aryl Hydrocarbon Hydroxylases
• Benzopyrans (chemistry, metabolism, therapeutic use)
• Chromatography, Liquid (methods)
• Cytochrome P-450 CYP3A
• Male
• Microsomes, Liver (drug effects, metabolism)
• Neuroprotective Agents (chemistry, metabolism, therapeutic use)
• Rats
• Rats, Sprague-Dawley
• Reperfusion Injury (drug therapy, metabolism)
• Spectrometry, Mass, Electrospray Ionization (methods)
• Tetrazoles (chemistry, metabolism, therapeutic use)