Biotransformation of trans-5-chloro-2-methyl-2,3,3a,12b-tetrahydro-1-H-dibenz[2,3:6,7]oxepin o [4,5-c]pyrrolidine maleate in rats.
The metabolism of trans-5-chloro-2-methyl-2,3,3a,12b-tetrahydro-1 H-dibenz[2,3:6,7]oxepinol [4,5-c]pyrrolidine maleate (Org 5222) labelled with [3H] or [14C] was investigated in Wistar rats. Metabolites were identified by mass spectrometry, 13C- and 1H-NMR analysis, IR spectroscopy and, wherever possible, by comparison with authentic reference compounds. The metabolites found in plasma, bile, faeces and urine revealed the processes of metabolism in which Org 5222 underwent oxidation to yield an N-oxide existing in two diastereoisomeric forms, or N-demethylation to yield a demethyl metabolite. A novel metabolite was found in bile, viz. a carbamate glucuronide, formed from an intermediate carbamic acid, derived from the addition of CO2 to the demethyl metabolite.
von dem Wildenberg
H M
HM
Drug Metabolism Department, Organon International B.V., Pharma Division Akzo, Oss, The Netherlands.
Delbressine
L P
LP
Kaspersen
F M
FM
Wagenaars
G N
GN
Jacobs
P L
PL
D000818:Animals; D014150:Antipsychotic Agents / Q000032:analysis / Q000378:metabolism*; D001646:Bile / Q000032:analysis / Q000378:metabolism; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D003986:Dibenzocycloheptenes; D003990:Dibenzoxepins / Q000032:analysis / Q000378:metabolism*; D005243:Feces / Q000032:analysis; D005260:Female; D006576:Heterocyclic Compounds, 4 or More Rings; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D013058:Mass Spectrometry; D051381:Rats; D011919:Rats, Inbred Strains; D013055:Spectrophotometry, Infrared
D014150:Antipsychotic Agents; D003986:Dibenzocycloheptenes; D003990:Dibenzoxepins; D006576:Heterocyclic Compounds, 4 or More Rings; C522667:asenapine