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-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.
Heinig
R
R
Institute of Pharmaceutical Chemistry, University of Münster, Fed. Rep. of Germany.
Delbressine
L P
LP
Kaspersen
F M
FM
Blaschke
G
G
D000818:Animals; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D005243:Feces / Q000737:chemistry; D008401:Gas Chromatography-Mass Spectrometry; D066298:In Vitro Techniques; D008297:Male; D008803:Mianserin / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D010084:Oxidation-Reduction; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013237:Stereoisomerism
D008803:Mianserin; D010634:Phenobarbital