Cytochrome P-450 activities in human and rat brain microsomes.

Details

Serval ID
serval:BIB_6EB25387D963
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Cytochrome P-450 activities in human and rat brain microsomes.
Journal
Brain research
Author(s)
Voirol P., Jonzier-Perey M., Porchet F., Reymond M.J., Janzer R.C., Bouras C., Strobel H.W., Kosel M., Eap C.B., Baumann P.
ISSN
0006-8993
Publication state
Published
Issued date
2000
Peer-reviewed
Oui
Volume
855
Number
2
Pages
235-43
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't - Publication Status: ppublish
Abstract
The role of cytochrome P450 in the metabolism of dextromethorphan, amitriptyline, midazolam, S-mephenytoin, citalopram, fluoxetine and sertraline was investigated in rat and human brain microsomes. Depending on the parameters, the limit of quantification using gas chromatography-mass spectrometry methods was between 1.6 and 20 pmol per incubation, which generally contained 1500 microg protein. Amitriptyline was shown to be demethylated to nortriptyline by both rat and human microsomes. Inhibition studies using ketoconazole, furafylline, sulfaphenazole, omeprazole and quinidine suggested that CYP3A4 is the isoform responsible for this reaction whereas CYP1A2, CYP2C9, CYP2C19 and CYP2D6 do not seem to be involved. This result was confirmed by using a monoclonal antibody against CYP3A4. Dextromethorphan was metabolized to dextrorphan in rat brain microsomes and was inhibited by quinidine and by a polyclonal antibody against CYP2D6. Only the addition of exogenous reductase allowed the measurement of this activity in human brain microsomes. Metabolites of the other substrates could not be detected, possibly due to an insufficiently sensitive method. It is concluded that cytochrome P450 activity in the brain is very low, but that psychotropic drugs could undergo a local cerebral metabolism which could have pharmacological and/or toxicological consequences.
Keywords
Aged, Aged, 80 and over, Animals, Brain, Cytochrome P-450 Enzyme System, Female, Humans, Isoenzymes, Kinetics, Male, Microsomes, Middle Aged, Rats, Rats, Wistar
Pubmed
Web of science
Create date
10/03/2008 10:53
Last modification date
20/08/2019 14:27
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