• Corpus ID: 35072376

May be Used as a Probe for CYP 2 D 6 Activity

  title={May be Used as a Probe for CYP 2 D 6 Activity},
Pinoline, 6-methoxy-1,2,3,4-tetrahydro-carboline, is a serotonin analog that selectively inhibits the activity of monoamine oxidase-A and shows antidepressant activity. Our previous study using a panel of recombinant cytochrome P450 (P450) enzymes suggests that pinoline O-demethylation may be selectively catalyzed by polymorphic CYP2D6. The current study, therefore, aimed to delineate the impact of CYP2D6 status on pinoline metabolism. Enzyme kinetic studies using recombinant CYP2D6 allelic… 

Figures and Tables from this paper


Screening for endogenous substrates reveals that CYP2D6 is a 5-methoxyindolethylamine O-demethylase.
It was ascertained that CYP2D6 does not significantly metabolize the endogenous phenylethylamine, nor the indolethylamines tryptamine, serotonin, 6-methoxytryptamine, and melatonin, norThe beta-carbolines harman, norharman and tryptoline, which are found in the brain and pineal gland.
Comparative Metabolic Capabilities and Inhibitory Profiles of CYP2D6.1, CYP2D6.10, and CYP2D6.17
There are mixed effects on the functionally reduced allelic variants in enzyme-substrate affinity or enzyme-inhibitor affinity, which is lower, higher, or comparable to that for CYP2D6.1.
Expression, Purification, Biochemical Characterization, and Comparative Function of Human Cytochrome P450 2D6.1, 2D6.2, 2D6.10, and 2D6.17 Allelic Isoforms
The intrinsic clearance of CYP2D6.2 enzyme was consistently decreased for each reaction examined, indicating that the ultra-rapid metabolizer phenotype sometimes associated with this genotype is not a function of the underlying amino acid substitutions.
Polymorphic Cytochrome P450 2D6: Humanized Mouse Model and Endogenous Substrates
Endogenous 5‐methoxyindolethylamines derived from 5‐hydroxytryptamine were identified as high‐affinity substrates of CYP2D6 that catalyzes their O‐demethylations with high enzymatic capacity and specificity, indicating a crucial step in a serotonin‐melatonin cycle.
Cytochrome P450 2D6: overview and update on pharmacology, genetics, biochemistry
The intricate genetics of the CYP2D6 polymorphism is becoming apparent at ever greater detail, applications in clinical practice are still rare, and more clinical studies are needed to show where patients benefit from drug dose adjustment based on their genotype.
Cytochrome P450 Expression and Regulation in CYP3A4/CYP2D6 Double Transgenic Humanized Mice
The difference in CYP3A4 expression and induction between male and female mice suggests that women may be more susceptible to CYP2D6-mediated drug-drug interactions, and the extent of drug- drug interactions could be substrate dependent.
Evaluation of probe drugs and pharmacokinetic metrics for CYP2D6 phenotyping
Application of the validation criteria suggests that dextromethorphan and debrisoquine are the best CYP2D6 phenotyping drugs, withbrisoquine having the problem of very limited availability as a therapeutic drug.
Indolealkylamines: Biotransformations and Potential Drug–Drug Interactions
  • A. Yu
  • Biology, Medicine
    The AAPS Journal
  • 2008
An important role for polymorphic cytochrome P450 2D6 (CYP2D 6) in the metabolism of IAA drugs of abuse has been revealed by recent studies, suggesting that variations in IAA metabolism, pharmaco- or toxicokinetics and dynamics can arise from distinct CYP2D6 status, and CYP1D6 polymorphism may represent an additional risk factor in the use of these IAAdrugs.
Quantitation of Human Cytochrome P450 2D6 Protein with Immunoblot and Mass Spectrometry Analysis
This study delineates the variability in absolute quantification of polymorphic CYP2D6 drug-metabolizing enzyme and compares immunoblot and nano liquid chromatography coupled to mass spectrometry (nano-LC/MS) methods in identification and relative quantification, and suggests that nano- LC/MS not only facilitates P450 quantitation but also provides genotypic information.
Expression and Functional Analysis of CYP 2 D 6 . 24 , CYP 2 D 6 . 26 , CYP 2 D 6 . 27 and CYP 2 D 7 Isozymes
The objectives of this study were to compare the drug-metabolizing activity of human CYP2D6.24 (I297L), CYP2D6.26 (I369T), CYP2D6.27 (E410K) allelic isoforms with wild-type CYP2D6.1, and to express