Corpus ID: 33852376

Use of quinidine inhibition to define the role of the sparteine/debrisoquine cytochrome P450 in metoprolol oxidation by human liver microsomes.

  title={Use of quinidine inhibition to define the role of the sparteine/debrisoquine cytochrome P450 in metoprolol oxidation by human liver microsomes.},
  author={S. Victoria Otton and H. Kim Crewe and Martin S. Lennard and Geoffrey T Tucker and H. F. Woods},
  journal={The Journal of pharmacology and experimental therapeutics},
  volume={247 1},
The oxidation of the beta adrenoceptor antagonist metoprolol exhibits genetic polymorphism of the sparteine/debrisoquine (SP/DB) type. The alpha-hydroxylation of metoprolol is absent in poor metabolizers, whereas metoprolol O-demethylation is only partially impaired, suggesting that an enzyme or enzymes other than cytochrome P450-SP/DB contribute to the latter reaction. Using inhibition by the quinidine/quinine isomer pair as a marker for the activity of cytochrome P450-SP/DB, the role of this… Expand
The role of cytochrome P4502D6 in the metabolism of paroxetine by human liver microsomes.
It is concluded that, in man, the initial step of paroxetine metabolism is performed by at least two enzymes, one of which is cytochrome P4502D6. Expand
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Variable contribution of cytochromes P450 2D6, 2C9 and 3A4 to the 4-hydroxylation of tamoxifen by human liver microsomes.
The findings indicate that the 4-hydroxylation of tamoxifen is catalysed almost exclusively by CYPs 2D6, 2C9 and 3A4 in human liver microsomes, but the marked between-subject variation in the contribution of these isoforms underlines the need to study metabolic reactions in a sufficient number of livers that are characterised with respect to a range of cytochrome P450 activities. Expand
Inhibition of CYP2D6 activity by treatment with propranolol and the role of 4-hydroxy propranolol.
Although treatment with propranolol 80 mg twice daily significantly decreases the catalytic function of CYP2D6, the inhibition is insufficient to result in phenocopying, and the reactive intermediate produced by further metabolism of 4OHP is probably scavenged effectively in vivo by glutathione and other nucleophiles. Expand
Propranolol oxidation by human liver microsomes--the use of cumene hydroperoxide to probe isoenzyme specificity and regio- and stereoselectivity.
The findings suggest that P450IID6 is involved in both the 4- and 5-hydroxylations of propranolol, but that these metabolites can also be formed by other P450 isoenzymes. Expand
Regio- and Stereo-Selective Oxidation of a Cardiovascular Drug, Metoprolol, Mediated by Cytochrome P450 2D and 3A Enzymes in Marmoset Livers
The results indicated that the major roles of P450 2D enzymes for the regio- and stereo-selectivity of metoprolol oxidation were similar between human and marmoset livers, but the minor roles ofP450 3A enzymes were unique to marmosets. Expand
The oxidative metabolism of metoprolol in human liver microsomes: inhibition by the selective serotonin reuptake inhibitors
The rank order of the SSRIs for inhibition of metoprolol metabolism is comparable to that reported in the literature for other CYP2D6 substrates, with fluxetine, norfluoxetine and paroxetines being the most potent. Expand
Involvement of human cytochrome P450 3A4 in reduced haloperidol oxidation
  • S. Kudo, M. Odomi
  • Chemistry, Medicine
  • European Journal of Clinical Pharmacology
  • 1998
It was concluded that CYP3A4, not CYP2D6, is the principal isoform of cytochrome P450 involved in the metabolic conversion of reduced haloperidol to haloperidsol and that haloperIDol has both stimulatory and inhibitory effects on CYP 2D6 activity. Expand