Enantioselective carbonyl reduction of eperisone in human liver microsomes
- Authors
- Yoo, Hye Hyun; Kim, Nam-Sun; Kim, Min Jung; Shin, Dongyun; Shin, Jae-Gook; Kim, Dong-Hyun
- Issue Date
- Sep-2011
- Publisher
- Taylor & Francis
- Keywords
- Eperisone; stereoselective metabolism; carbonyl reduction; microsomes; 11 beta-hydroxysteroid dehydrogenase type 1
- Citation
- Xenobiotica, v.41, no.9, pp.758 - 763
- Indexed
- SCIE
SCOPUS
- Journal Title
- Xenobiotica
- Volume
- 41
- Number
- 9
- Start Page
- 758
- End Page
- 763
- URI
- https://scholarworks.bwise.kr/erica/handle/2021.sw.erica/37211
- DOI
- 10.3109/00498254.2011.576277
- ISSN
- 0049-8254
- Abstract
- 1. Eperisone, 4-ethyl-2-methyl-3-piperidinopropiophenone, is a centrally acting muscle relaxant widely used to relieve muscle stiffness and back pain. In this study, enantioselectivity for carbonyl reduction of eperisone was investigated in human liver microsomes, and the enzymes involved in the carbonyl reduction were characterised. 2. Carbonyl reduction of eperisone predominantly occurred in microsomal fractions and 11 beta-hydroxysteroid dehydrogenase type 1(11 beta-HSD 1) played a major role in this reaction as judged by selective inhibition of the activity by BVT-14225 and KR-66344. The kinetic study with (+)-S- and (-)-R-eperisone showed that the formation of the carbonyl reduced metabolite (M5) from the (-)-R-isomer was more efficient than that from the (-)-S-isomer. 3. As eperisone is a racemic compound with one chiral centre, the carbonyl reduced metabolite of eperisone (M5) may have four possible diastereoisomeric structures. Chiral separation of incubation mixtures of racemic eperisone with human liver microsome revealed that (1S, 2S)-M5 and (1R, 2R)-M5 were generated specifically from (+)-S-and (-)-R-eperisone, respectively. Selective formation of anti-diastereomers was further confirmed by incubation of individual enantiomer with microsomes. 4. Carbonyl reduction of eperisone by microsomal 11 beta-HSD 1 may significantly contribute to the metabolic disposition of eperisone in human and (-)-R-isomer is preferentially reduced by this enzyme.
- Files in This Item
-
Go to Link
- Appears in
Collections - COLLEGE OF PHARMACY > DEPARTMENT OF PHARMACY > 1. Journal Articles
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.