INT56870

Context Info Confidence 0.78 First Reported 1993 Last Reported 2010 Negated 9 Speculated 2 Reported most in Abstract Documents 87 Total Number 89 Disease Relevance 8.83 Pain Relevance 37.53

mitochondrion (CYP2D6) small molecule metabolic process (CYP2D6) oxidoreductase activity (CYP2D6) endoplasmic reticulum (CYP2D6)

Anatomy Link Frequency brain 7 liver 6 white blood cells 3 bands 3 blood 2 CYP2D6 (Homo sapiens)

Pain Link Frequency Relevance Heat Morphine 335 100.00 Codeine 200 100.00 Dextromethorphan 335 99.88 fluoxetine 94 99.84 Paracetamol 45 99.82 tramadol 26 99.48 Duloxetine 185 99.24 Opioid 343 99.00 analgesia 44 98.96 sSRI 54 98.92

Disease Link Frequency Relevance Heat Toxicity 22 99.18 Pain 170 97.78 Nicotine Addiction 81 97.56 Breast Cancer 31 96.36 Respiratory Failure 2 95.00 Injury 12 94.88 Pressure Volume 2 Under Development 18 94.76 Neurological Disease 6 94.04 Sprains And Strains 18 92.80 Urological Neuroanatomy 6 91.92

Sentences Mentioned In

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Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

Following administration of exogenous codeine the biotransformation to morphine is catalyzed by CYP2D6, which exhibits a genetic so-called debrisoquine/sparteine polymorphism which is expressed in two phenotypes, the extensive and poor metaboliser phenotypes.

Gene_expression (expressed) of CYP2D6 associated with morphine and codeine

1) Confidence 0.78 Published 1994 Journal J. Pharmacol. Exp. Ther. Section Abstract Doc Link 8113966 Disease Relevance 0 Pain Relevance 1.05

We investigated the demethylenation of MDMA and dextromethorphan (DEX), as a comparison drug, in reconstituted microsomes expressing the variant CYP2D6 alleles (*)2, (*)10, and (*)17, all of which have been linked to decreased enzyme activity.

Gene_expression (expressing) of CYP2D6 associated with dextromethorphan

2) Confidence 0.78 Published 2002 Journal Biochem. Pharmacol. Section Abstract Doc Link 12110370 Disease Relevance 0.09 Pain Relevance 0.23

In this study, the regional and cellular expression of CYP2D6 transcripts and proteins in postmortem brain tissues of three individuals was analysed.

Spec (analysed) Gene_expression (expression) of CYP2D6 in brain

3) Confidence 0.78 Published 2001 Journal Pharmacogenetics Section Abstract Doc Link 11337939 Disease Relevance 0 Pain Relevance 0.32

Cellular localization and regional distribution of CYP2D6 mRNA and protein expression in human brain.

Gene_expression (expression) of CYP2D6 in brain

4) Confidence 0.78 Published 2001 Journal Pharmacogenetics Section Title Doc Link 11337939 Disease Relevance 0 Pain Relevance 0.41

These results provide clear evidence of CYP2D6 expression in certain regions of the CNS and may indicate the role CYP2D6 plays in a number of drug interactions that are of potential clinical importance for neurological diseases.

Gene_expression (expression) of CYP2D6 in CNS associated with neurological disease and central nervous system

5) Confidence 0.78 Published 2001 Journal Pharmacogenetics Section Abstract Doc Link 11337939 Disease Relevance 0.09 Pain Relevance 0.46

The O-demethylation ratio of dextromethorphan that expressed CYP2D6 activity in 19 patients receiving fluoxetine fell in the region of the antimode separating the O-demethylation ratio values observed in 208 extensive metabolizers from 15 poor metabolizers of a control group of healthy subjects.

Gene_expression (expressed) of CYP2D6 associated with dextromethorphan and fluoxetine

6) Confidence 0.78 Published 1993 Journal Clin. Pharmacol. Ther. Section Abstract Doc Link 8477556 Disease Relevance 0.07 Pain Relevance 0.53

The latter pathway depends on the genetically polymorphic CYP2D6 which is absent in 7% of the white population (PM) and present in the remainder (EM).

Neg (absent) Gene_expression (present) of CYP2D6

7) Confidence 0.78 Published 1995 Journal Pharmacogenetics Section Abstract Doc Link 8845855 Disease Relevance 0.26 Pain Relevance 1.32

CYP2D6, which is present in the liver and presumably also in the brain, is not expressed in subjects who are poor metabolisers of the sparteine/debrisoquine type.

Neg (not) Gene_expression (expressed) of CYP2D6 in brain

8) Confidence 0.78 Published 1993 Journal Pain Section Abstract Doc Link 8351162 Disease Relevance 0.56 Pain Relevance 1.23

CYP2D6, which is present in the liver and presumably also in the brain, is not expressed in subjects who are poor metabolisers of the sparteine/debrisoquine type.

Gene_expression (present) of CYP2D6 in brain

9) Confidence 0.78 Published 1993 Journal Pain Section Abstract Doc Link 8351162 Disease Relevance 0.52 Pain Relevance 1.19

Expression, purification, biochemical characterization, and comparative function of human cytochrome P450 2D6.1, 2D6.2, 2D6.10, and 2D6.17 allelic isoforms.

Gene_expression (Expression) of cytochrome P450 2D6

10) Confidence 0.78 Published 2002 Journal J. Pharmacol. Exp. Ther. Section Title Doc Link 12438554 Disease Relevance 0 Pain Relevance 0.41

Active CYP2D6.1, 2, 10, and 17 holo-enzymes were expressed in vitro and purified to a high degree of homogeneity as confirmed with SDS-polyacrylamide gel electrophoresis, CO-difference spectroscopy, and mass spectral analysis.

Gene_expression (expressed) of CYP2D6

11) Confidence 0.78 Published 2002 Journal J. Pharmacol. Exp. Ther. Section Abstract Doc Link 12438554 Disease Relevance 0 Pain Relevance 0.28

The formation of NAPQI from APAP by cDNA-expressed CYP2D6 was examined.

Gene_expression (expressed) of CYP2D6 associated with paracetamol

12) Confidence 0.78 Published 2000 Journal Drug Metab. Dispos. Section Abstract Doc Link 11095574 Disease Relevance 0.08 Pain Relevance 0.87

The analgesic effect of codeine is mediated by its metabolite morphine, which is formed by the polymorphically expressed enzyme CYP2D6; therefore poor metabolizers have no analgesia after administration of codeine.

Gene_expression (expressed) of CYP2D6 associated with analgesia, morphine and codeine

13) Confidence 0.78 Published 1997 Journal Clin. Pharmacol. Ther. Section Abstract Doc Link 9129563 Disease Relevance 0.18 Pain Relevance 1.10

At pharmacological concentrations of S-fluoxetine, S-norfluoxetine formation rates in the bank of microsomes were found to correlate only with CYP2D6 catalytic activity and only expressed CYP2D6 was found to be capable of forming S-norfluoxetine.

Gene_expression (expressed) of CYP2D6 associated with fluoxetine

14) Confidence 0.78 Published 2001 Journal J. Pharmacol. Exp. Ther. Section Abstract Doc Link 11356927 Disease Relevance 0 Pain Relevance 0.33

In this report, evidence is presented that the O-demethylation of ibogaine observed in human hepatic microsomes is catalyzed primarily by the polymorphically expressed cytochrome P-4502D6 (CYP2D6).

Gene_expression (expressed) of CYP2D6

15) Confidence 0.77 Published 1998 Journal Drug Metab. Dispos. Section Abstract Doc Link 9698290 Disease Relevance 0.09 Pain Relevance 0.18

In this report, evidence is presented that the O-demethylation of ibogaine observed in human hepatic microsomes is catalyzed primarily by the polymorphically expressed cytochrome P-4502D6 (CYP2D6).

Gene_expression (expressed) of cytochrome P-4502D6

16) Confidence 0.77 Published 1998 Journal Drug Metab. Dispos. Section Abstract Doc Link 9698290 Disease Relevance 0.09 Pain Relevance 0.18

Endogenous morphine signaling via nitric oxide regulates the expression of CYP2D6 and COMT: autocrine/paracrine feedback inhibition.

Gene_expression (expression) of CYP2D6 associated with narcan and morphine

17) Confidence 0.76 Published 2008 Journal Addict Biol Section Title Doc Link 17573783 Disease Relevance 0 Pain Relevance 0.66

Furthermore, exposure of white blood cells to 10(-6) M S-nitroso-N-acetyl-DL-penicillamine (SNAP), a nitric oxide (NO) donor, reduced the expression of CYP2D6 and COMT.

Gene_expression (expression) of CYP2D6 in white blood cells

18) Confidence 0.76 Published 2008 Journal Addict Biol Section Abstract Doc Link 17573783 Disease Relevance 0 Pain Relevance 0.97

The verification of the microarray data was accomplished via real-time Taqman reverse transcriptase polymerase chain reaction (RT-PCR) focused on CYP2D6 and COMT expression in different blood samples treated with morphine.

Gene_expression (expression) of CYP2D6 in blood associated with morphine

19) Confidence 0.76 Published 2008 Journal Addict Biol Section Abstract Doc Link 17573783 Disease Relevance 0 Pain Relevance 0.63

The analysis showed similar changes in the expression of CYP2D6 and COMT mRNA.

Gene_expression (expression) of CYP2D6

20) Confidence 0.76 Published 2008 Journal Addict Biol Section Abstract Doc Link 17573783 Disease Relevance 0 Pain Relevance 0.69

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