PMID- 1678603
OWN - NLM
STAT- MEDLINE
DCOM- 19910916
LR  - 20190623
IS  - 0006-2952 (Print)
IS  - 0006-2952 (Linking)
VI  - 42
IP  - 5
DP  - 1991 Aug 8
TI  - Metabolism of methylenedioxyphenyl compounds by rabbit liver preparations. 
      Participation of different cytochrome P450 isozymes in the demethylenation 
      reaction.
PG  - 1061-7
AB  - The cytochrome P450-mediated oxidative demethylenation of the benzo-1,3-dioxoles 
      (methylenedioxyphenyl compounds, MDPs), methylenedioxybenzene (MDB), 
      methylenedioxyamphetamine (MDA), and methylenedioxymethamphetamine (MDMA), by 
      rabbit liver microsomes and cytochrome P450IIB4 (CYP2B4) was examined. Material 
      balance studies indicated that demethylenation to catechol derivatives is a major 
      metabolic pathway for MDB, MDA and MDMA. The reactions required NADPH and were 
      inhibited by CO/O2 (4:1, v/v). Biphasic double-reciprocal plots of MDMA, MDA and 
      MDB oxidation suggested participation of more than one isozyme of cytochrome P450 
      in the reaction. Phenobarbital (PB) induction was selective in that the Vmax 
      values for MDB were increased but not those for MDA and MDMA. Exposure of liver 
      microsomes from PB-pretreated animals to phencyclidine (PCP) markedly suppressed 
      MDB oxidation but had little effect on MDA and MDMA demethylenation. 
      Reconstitution experiments with CYP2B4 demonstrated that MDB is a good substrate 
      for the isozyme; but the relative demethylenation activities for MDA and MDMA 
      were 1 and 2% of that for MDB. These results indicate that the PB-inducible 
      isozymes such as CYP2B4 appear to play an important role in MDB demethylenation, 
      whereas MDA and MDMA oxidation is mediated mainly by constitutive isozymes.
FAU - Kumagai, Y
AU  - Kumagai Y
AD  - Department of Pharmacology, University of California School of Medicine, Los 
      Angeles 90024-1735.
FAU - Wickham, K A
AU  - Wickham KA
FAU - Schmitz, D A
AU  - Schmitz DA
FAU - Cho, A K
AU  - Cho AK
LA  - eng
GR  - DA 04206/DA/NIDA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Biochem Pharmacol
JT  - Biochemical pharmacology
JID - 0101032
RN  - 0 (Dioxolanes)
RN  - 0 (Dioxoles)
RN  - 0 (Isoenzymes)
RN  - 4764-17-4 (3,4-Methylenedioxyamphetamine)
RN  - 9035-51-2 (Cytochrome P-450 Enzyme System)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
RN  - YQE403BP4D (Phenobarbital)
SB  - IM
MH  - 3,4-Methylenedioxyamphetamine/analogs & derivatives/metabolism
MH  - Animals
MH  - Biotransformation
MH  - Chromatography, High Pressure Liquid
MH  - Cytochrome P-450 Enzyme System/isolation & purification/*metabolism
MH  - Dioxolanes/metabolism
MH  - Dioxoles/*metabolism
MH  - Gas Chromatography-Mass Spectrometry
MH  - Isoenzymes/isolation & purification/*metabolism
MH  - Kinetics
MH  - Liver/*metabolism
MH  - Male
MH  - Microsomes, Liver/drug effects/enzymology
MH  - N-Methyl-3,4-methylenedioxyamphetamine
MH  - Phenobarbital/pharmacology
MH  - Rabbits
EDAT- 1991/08/08 00:00
MHDA- 1991/08/08 00:01
CRDT- 1991/08/08 00:00
PHST- 1991/08/08 00:00 [pubmed]
PHST- 1991/08/08 00:01 [medline]
PHST- 1991/08/08 00:00 [entrez]
AID - 0006-2952(91)90289-H [pii]
AID - 10.1016/0006-2952(91)90289-h [doi]
PST - ppublish
SO  - Biochem Pharmacol. 1991 Aug 8;42(5):1061-7. doi: 10.1016/0006-2952(91)90289-h.