Eur J Drug Metab Pharmacokinet. 1997 Apr-Jun;22(2):165-71.  

Interaction of chlormezanone with rat liver microsomes and its degradation.

Klinger W, Oelschlager H, Karge E, Rothley D.

Institut fur Pharmakologie und Toxikologie, Friedrich-Schiller-Universitat,
Jena, Germany.

Chlormezanone binds to oxidized cytochrome P450 in rat liver microsomes with a
binding curve according to type I like hexobarbital but less pronounced and with
a general shift to the left. Ethylmorphine N-demethylation, ethoxycoumarin and
ethoxyresorufin O-deethylation are inhibited by chlormezanone in mM
concentrations only whereas pentoxyresorufin O-depentylation is inhibited by
about 50% in microM concentrations. Luminol and lucigenin amplified
chemiluminescence indicating the formation of reactive oxygen species was not
influenced in concentration ranges between mM and microM, whereas NADPH/Fe
stimulated lipid peroxidation showed a tendency of inhibition. But scavenger
activity could not be demonstrated: the zymosan stimulated chemiluminescence of
whole blood was not influenced significantly. The degradation process of
chlormezanone was elucidated. The first step involves ring opening by chemical
hydrolysis with subsequent formation of an unstable acylhalfaminal which is the
source of 4-chlorobenzaldehyde. This aldehyde undergoes enzymatically controlled
oxidation to 4-chlorobenzoic acid which is the parent compound of following
phase II reactions. The second degradation product is
2-carboxyethane-sulfinic-acid-N-methylamide, which is hydrolyzed very quickly.
Neither oxidation of the sulfinic acid or its N-methylamide derivative could be
observed nor N-demethylation of chlormezanone.

PMID: 9248786 [PubMed - indexed for MEDLINE]