Enantiomeric aspects of the metabolism of mianserin in rats

After separate administration of mianserin (CAS 24219-97-4) enantiomers to rats, the hydroxy-metabolites of S-mianserin were excreted mainly as conjugates whereas the amount of free phenolic metabolites was greater after administration of the R-enantiomer. The sulphate-conjugate of 8-hydroxy-mianser...

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Published inArzneimittel-Forschung Vol. 43; no. 7; p. 709
Main Authors Heinig, R, Delbressine, L P, Kaspersen, F M, Blaschke, G
Format Journal Article
LanguageEnglish
Published Germany 01.07.1993
Subjects
Animals
Biotransformation
Chromatography, High Pressure Liquid
Chromatography, Thin Layer
Feces - chemistry
Gas Chromatography-Mass Spectrometry
In Vitro Techniques
Male
Mianserin - chemistry
Mianserin - metabolism
Mianserin - pharmacokinetics
Microsomes, Liver - drug effects
Microsomes, Liver - metabolism
Oxidation-Reduction
Phenobarbital - pharmacology
Rats
Rats, Wistar
Stereoisomerism
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Summary:After separate administration of mianserin (CAS 24219-97-4) enantiomers to rats, the hydroxy-metabolites of S-mianserin were excreted mainly as conjugates whereas the amount of free phenolic metabolites was greater after administration of the R-enantiomer. The sulphate-conjugate of 8-hydroxy-mianserin was stereoselectively found in faeces only after administration of S-mianserin. Based on in vitro experiments with sulphatase, the stability of this conjugate towards enzymic hydrolysis appears a likely explanation. In vitro experiments with liver homogenates of rats revealed little enantioselectivity with respect to oxidative metabolism. After prior enzyme induction with phenobarbital, however, enantioselectivity with regard to N-oxidation was found. The 3-oxo-mianserin metabolite, found in vitro, is most likely the product of a rearrangement of mianserin-N-oxide. N-formyl-demethyl-mianserin, identified in vitro, is considered to be an artefact.
ISSN:0004-4172