Biotransformation of mirtazapine by Cunninghamella elegans.
The fungus Cunninghamella elegans was used as a microbial model of mammalian metabolism to biotransform the tetracyclic antidepressant drug mirtazapine, which is manufactured as a racemic mixture of R(-)- and S(+)-enantiomers. In 168 h, C. elegans transformed 91% of the drug into the following seven metabolites: 8-hydroxymirtazapine, N-desmethyl-8-hydroxymirtazapine, N-desmethylmirtazapine, 13-hydroxymirtazapine, mirtazapine N-oxide, 12-hydroxymirtazapine, and N-desmethyl-13-hydroxymirtazapine. Circular dichroism spectral analysis of unused mirtazapine indicated that it was slightly enriched with the R(-)-enantiomer. When the fungus was treated with the optically pure forms of the drug, the S(+)-enantiomer produced all seven metabolites whereas the R(-)-enantiomer produced only 8-hydroxymirtazapine, N-desmethyl-8-hydroxymirtazapine, N-desmethylmirtazapine, and mirtazapine N-oxide. C. elegans produced five mammalian and two novel metabolites and is therefore a suitable microbial model for mirtazapine metabolism.
Moody
Joanna D
JD
Division of Microbiology, National Center for Toxicological Research, Jefferson, Arkansas 72079, USA.
Freeman
James P
JP
Fu
Peter P
PP
Cerniglia
Carl E
CE
D000928:Antidepressive Agents / Q000378:metabolism*; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D002942:Circular Dichroism; D020093:Cunninghamella / Q000378:metabolism*; D003497:Cyclic N-Oxides / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D008803:Mianserin / Q000031:analogs & derivatives* / Q000378:metabolism*; D000078785:Mirtazapine; D013237:Stereoisomerism
D000928:Antidepressive Agents; D003497:Cyclic N-Oxides; C517417:mirtazapine-N-oxide; D008803:Mianserin; D000078785:Mirtazapine