Enantioselective metabolism of camazepam by rat liver microsomes.
Camazepam [3-(N,N-dimethyl)carbamoyloxy-7-chloro-1-methyl-1, 3-dihydro-5-phenyl-2H-1,4-benzodiazepin-2-one, CMZ] possesses anxiolytic, anticonvulsant, muscle relaxant and hypnotic properties. CMZ is clinically used as a racemate. The enantioselective metabolism of racemic CMZ by rat liver microsomes was studied. Major metabolites were isolated by normal-phase and reversed-phase liquid chromatography (LC) and further characterized by UV absorption, mass, and circular dichroism spectral analyses, and by chiral stationary phase LC analysis. Following an in vitro incubation of rac-CMZ, the unmetabolized CMZ was found to be enriched (S)-CMZ, indicating that the R-enantiomer was enantioselectively metabolized. Two of the most abundant metabolites, formed by hydroxylation and demethylation of a methyl group of the N,N-dimethylcarbamyloxy side chain, were found to be enriched in the R-enantiomer. The results indicated that the (R)-CMZ was metabolized at a faster rate than (S)-CMZ by rat liver microsomes.
Lu
X L
XL
Department of Pharmacology, F. Edward Hébert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814-4799.
Yang
S K
SK
D000818:Animals; D002853:Chromatography, Liquid; D002942:Circular Dichroism; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D013058:Mass Spectrometry; D008862:Microsomes, Liver / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013056:Spectrophotometry, Ultraviolet; D013237:Stereoisomerism; D013693:Temazepam / Q000302:isolation & purification / Q000378:metabolism*
D013693:Temazepam