Metabolic activation of the phenothiazine antipsychotics chlorpromazine and thioridazine to electrophilic iminoquinone species in human liver microsomes and recombinant P450s

Chemico-Biological Interactions

Volumn 181, Issue 2, 2009, Pages 220-226

  Wen, Bo ^a   Zhou, Mingyan ^b  

^a Roche Palo Alto ^*  (United States)

^b XenoPort Inc   (United States)

Author keywords

Bioactivation; Chlorpromazine; Hepatotoxicity; Phenothiazine; Quinone imine; Reactive metabolites; Thioridazine

Indexed keywords

7 HYDROXYCHLORPROMAZINE; 7 HYDROXYTHIORIDAZINE; CHLORPROMAZINE; CYTOCHROME P450; CYTOCHROME P450 1A2; CYTOCHROME P450 2D6; DRUG METABOLITE; GLUTATHIONE; PYRROLOIMINOQUINONE DERIVATIVE; QUINIDINE; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE; THIORIDAZINE; UNCLASSIFIED DRUG;

ARTICLE; COVALENT BOND; DRUG CONJUGATION; DRUG HYDROXYLATION; DRUG STRUCTURE; ENZYME INHIBITION; HUMAN; LIQUID CHROMATOGRAPHY; LIVER MICROSOME METABOLISM; MASS SPECTROMETRY; METABOLIC ACTIVATION; PROTEIN EXPRESSION; SOLID PHASE EXTRACTION; TANDEM MASS SPECTROMETRY;

ANTIPSYCHOTIC AGENTS; BIOTRANSFORMATION; CHLORPROMAZINE; CHROMATOGRAPHY, HIGH PRESSURE LIQUID; CYTOCHROME P-450 CYP2D6; DOSE-RESPONSE RELATIONSHIP, DRUG; ENZYME INHIBITORS; GLUTATHIONE; HUMANS; MICROSOMES, LIVER; QUINIDINE; QUINONES; TANDEM MASS SPECTROMETRY; THIORIDAZINE;

EID: 68849116514     PISSN: 00092797     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.cbi.2009.05.014     Document Type: Article

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