Interaction of chlormezanone enantiomers with rat liver microsomes.
Both chlormezanone enantiomers, for the first time obtained by enantiospecific HPLC with a 100% yield, bind to oxidized cytochrome P-450 in rat liver microsomes with a binding curve according to type I, similar to hexobarbital but less pronounced. There are no differences between the binding curves of the two enantiomers. Ethylmorphine N-demethylation, ethoxycoumarin and ethoxyresorufin O-deethylation are inhibited by both chlormezanone enantiomers at 0.1-1 mM concentrations: no differences could be found. Luminol and lucigenin amplified chemiluminescence indicating the formation of reactive oxygen species was not influenced by either enantiomer in concentration ranges between millimolar and micromolar, whereas hydrogen peroxide formation was inhibited. NADPH/Fe stimulated lipid peroxidation was not influenced. Scavenger activity could not be demonstrated: the zymosan stimulated whole blood chemiluminescence was not influenced significantly.
Institut für Pharmakologie und Toxikologie, Friedrich-Schiller-Universität Jena, Germany.
W
W
Klinger
H
H
Oelschläger
D
D
Rothley
E
E
Karge
A
A
Seeling
D000166:Acridines / Q000737:chemistry; D000701:Analgesics, Opioid / Q000378:metabolism; D000818:Animals; D000925:Anticoagulants / Q000378:metabolism; D002720:Chlormezanone / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D003374:Coumarins / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D005036:Ethylmorphine / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism; D007202:Indicators and Reagents / Q000737:chemistry; D015227:Lipid Peroxidation / Q000187:drug effects; D008163:Luminescent Measurements; D008165:Luminol / Q000737:chemistry; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism*; D009125:Muscle Relaxants, Central / Q000378:metabolism*; D010078:Oxazines / Q000378:metabolism; D011485:Protein Binding; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D013237:Stereoisomerism; D015054:Zymosan / Q000737:chemistry
D000166:Acridines; D000701:Analgesics, Opioid; D000925:Anticoagulants; D003374:Coumarins; D007202:Indicators and Reagents; D009125:Muscle Relaxants, Central; D010078:Oxazines; D017382:Reactive Oxygen Species; C033472:10,10'-dimethyl-9,9'-biacridinium; C007649:ethoxyresorufin; D008165:Luminol; D015054:Zymosan; D003577:Cytochrome P-450 Enzyme System; D006861:Hydrogen Peroxide; D002720:Chlormezanone; D005036:Ethylmorphine