INT15913

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Context Info
Confidence 0.59
First Reported 1991
Last Reported 2010
Negated 3
Speculated 2
Reported most in Abstract
Documents 174
Total Number 176
Disease Relevance 22.45
Pain Relevance 70.91

This is a graph with borders and nodes. Maybe there is an Imagemap used so the nodes may be linking to some Pages.

mitochondrion (CYP2D6) small molecule metabolic process (CYP2D6) oxidoreductase activity (CYP2D6)
endoplasmic reticulum (CYP2D6)
Anatomy Link Frequency
liver 10
plasma 7
blood 3
urine 2
central nervous system 1
CYP2D6 (Homo sapiens)
Pain Link Frequency Relevance Heat
fluoxetine 353 100.00 Very High Very High Very High
antidepressant 250 100.00 Very High Very High Very High
Potency 78 100.00 Very High Very High Very High
sSRI 398 99.98 Very High Very High Very High
Morphine 177 99.98 Very High Very High Very High
Dextromethorphan 377 99.80 Very High Very High Very High
tricyclic antidepressant 164 99.76 Very High Very High Very High
Analgesic 81 99.72 Very High Very High Very High
methadone 791 99.70 Very High Very High Very High
Duloxetine 285 99.70 Very High Very High Very High
Disease Link Frequency Relevance Heat
Hepatotoxicity 25 99.84 Very High Very High Very High
Poisoning 15 99.52 Very High Very High Very High
Cirrhosis 11 99.44 Very High Very High Very High
Toxicity 243 99.18 Very High Very High Very High
Substance Withdrawal Syndrome 123 99.00 Very High Very High Very High
Disease Progression 7 98.52 Very High Very High Very High
Hepatic Insufficiency 11 98.28 Very High Very High Very High
Overdose 36 98.24 Very High Very High Very High
Hypoalagesia 4 98.12 Very High Very High Very High
Disease 223 97.28 Very High Very High Very High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
In conclusion, compounds known to be potent CYP2D6 inhibitors inhibited timolol metabolism in in vitro experiments.
Negative_regulation (inhibitors) of CYP2D6
1) Confidence 0.59 Published 2010 Journal Basic Clin. Pharmacol. Toxicol. Section Abstract Doc Link 19912165 Disease Relevance 0.06 Pain Relevance 0.35
Apparent mechanism-based inhibition of human CYP2D6 in vitro by paroxetine: comparison with fluoxetine and quinidine.
Negative_regulation (inhibition) of CYP2D6 associated with fluoxetine
2) Confidence 0.59 Published 2003 Journal Drug Metab. Dispos. Section Title Doc Link 12584155 Disease Relevance 0 Pain Relevance 0.19
Paroxetine, a selective serotonin reuptake inhibitor, is a potent inhibitor of cytochrome P450 2D6 (CYP2D6) activity, but the mechanism of inhibition is not established.
Negative_regulation (inhibitor) of CYP2D6 associated with ssri
3) Confidence 0.59 Published 2003 Journal Drug Metab. Dispos. Section Abstract Doc Link 12584155 Disease Relevance 0 Pain Relevance 0.17
In contrast, quinidine and fluoxetine, both of which are inhibitors of CYP2D6 activity, did not exhibit a preincubation-dependent increase in inhibitory potency.
Negative_regulation (inhibitors) of CYP2D6 associated with potency and fluoxetine
4) Confidence 0.59 Published 2003 Journal Drug Metab. Dispos. Section Abstract Doc Link 12584155 Disease Relevance 0 Pain Relevance 0.31
These data are consistent with mechanism-based inhibition of CYP2D6 by paroxetine but not by quinidine or fluoxetine.
Negative_regulation (inhibition) of CYP2D6 associated with fluoxetine
5) Confidence 0.59 Published 2003 Journal Drug Metab. Dispos. Section Abstract Doc Link 12584155 Disease Relevance 0 Pain Relevance 0.32
Potent inhibition of cytochrome P450 2D6 (CYP2D6) in human liver microsomes by fluoxetine and its major metabolite norfluoxetine was confirmed (apparent inhibition constant values, 0.2 mumol/L).
Negative_regulation (inhibition) of CYP2D6 in liver associated with fluoxetine
6) Confidence 0.59 Published 1993 Journal Clin. Pharmacol. Ther. Section Abstract Doc Link 8477556 Disease Relevance 0 Pain Relevance 0.28
This reaction was inhibited by fluoxetine and its normetabolite in liver microsomes from both extensive and poor metabolizer individuals, indicating that these compounds are not selective inhibitors of CYP2D6 activity.
Neg (not) Negative_regulation (inhibitors) of CYP2D6 in liver associated with fluoxetine
7) Confidence 0.59 Published 1993 Journal Clin. Pharmacol. Ther. Section Abstract Doc Link 8477556 Disease Relevance 0.08 Pain Relevance 0.55
Inhibition of CYP2D6 activity in patients undergoing treatment with fluoxetine or other serotonin uptake inhibitors could contribute to toxicity or attenuated response from concurrent medications that are substrates of this enzyme.
Negative_regulation (Inhibition) of CYP2D6 associated with toxicity, serotonin and fluoxetine
8) Confidence 0.59 Published 1993 Journal Clin. Pharmacol. Ther. Section Abstract Doc Link 8477556 Disease Relevance 0.10 Pain Relevance 0.59
A number of drugs have been clinically implicated in major drug-drug interactions (DDI) via CYP2D6 inhibition.
Negative_regulation (inhibition) of CYP2D6
9) Confidence 0.59 Published 2009 Journal Curr. Med. Chem. Section Abstract Doc Link 19689286 Disease Relevance 0 Pain Relevance 0
Medicinal chemistry strategies to reduce CYP2D6 inhibitory activity of lead candidates.
Negative_regulation (reduce) of CYP2D6 associated with analgesic
10) Confidence 0.59 Published 2009 Journal Curr. Med. Chem. Section Title Doc Link 19689286 Disease Relevance 0 Pain Relevance 0.20
This is true unless there are other, acceptable alternatives that provide similar potential benefits, as in the case for postmenopausal women contemplating tamoxifen as part of their adjuvant hormonal therapy and for women on tamoxifen who are taking selective serotonin reuptake inhibitors, such as paroxetine and fluoxetine, that are potent inhibitors of CYP2D6.
Negative_regulation (inhibitors) of CYP2D6 associated with ssri and fluoxetine
11) Confidence 0.59 Published 2007 Journal Breast Cancer Res Section Body Doc Link PMC1868921 Disease Relevance 0.10 Pain Relevance 0.15
In addition, certain inhibitors of the CYP2D6 enzyme, such as the selective serotonin reuptake inhibitors, which are frequently given to breast cancer patients to combat hot flashes and treat depression, may result in altered tamoxifen activity, and lead to poorer clinical outcomes [2,4].
Negative_regulation (inhibitors) of CYP2D6 associated with hot flashes, depression, breast cancer and ssri
12) Confidence 0.59 Published 2007 Journal Breast Cancer Res Section Body Doc Link PMC1868921 Disease Relevance 0.54 Pain Relevance 0.10
Under what circumstances should patients considering tamoxifen as an adjuvant therapy be tested for CYP2D6 and under what circumstances should patients taking tamoxifen avoid potent inhibitors of CYP2D6?
Negative_regulation (inhibitors) of CYP2D6
13) Confidence 0.59 Published 2007 Journal Breast Cancer Res Section Body Doc Link PMC1868921 Disease Relevance 0.46 Pain Relevance 0.08
Dependence of codeine hypoalgesia on morphine formation via CYP2D6 makes this effect liable to interaction with drugs that are inhibitors of CYP2D6.
Negative_regulation (inhibitors) of CYP2D6 associated with addiction, hypoalgesia, morphine and codeine
14) Confidence 0.59 Published 1995 Journal Pharmacogenetics Section Abstract Doc Link 8845855 Disease Relevance 0.39 Pain Relevance 2.25
The kinetics of hydrocodone after a single oral dose and its partial metabolic clearance to hydromorphone were investigated in five extensive metabolizers of dextromethorphan, six poor metabolizers, and four extensive metabolizers after pretreatment with quinidine, a selective inhibitor of CYP2D6 activity.
Negative_regulation (inhibitor) of CYP2D6 associated with dextromethorphan
15) Confidence 0.59 Published 1993 Journal Clin. Pharmacol. Ther. Section Abstract Doc Link 7693389 Disease Relevance 0 Pain Relevance 0.23
However, over the first hour after dosing, the extensive metabolizers reported more "good opiate effects" and fewer "bad opiate effects" than poor metabolizers and extensive metabolizers in whom CYP2D6 was inhibited by quinidine.
Negative_regulation (inhibited) of CYP2D6 associated with opiate
16) Confidence 0.59 Published 1993 Journal Clin. Pharmacol. Ther. Section Abstract Doc Link 7693389 Disease Relevance 0 Pain Relevance 0.27
Phentermine also did not inhibit P450-2D6.
Negative_regulation (inhibit) of P450-2D6
17) Confidence 0.59 Published 1998 Journal J Clin Psychopharmacol Section Abstract Doc Link 9690701 Disease Relevance 0 Pain Relevance 0.16
However, D- and L-fenfluramine significantly inhibited P450-2D6 activity as measured by dextromethorphan O-demethylation, with mean 50% inhibitory concentrations (15.1 microM) within one order of magnitude of that for fluoxetine (2.7 microM).
Negative_regulation (inhibited) of P450-2D6 associated with dextromethorphan and fluoxetine
18) Confidence 0.59 Published 1998 Journal J Clin Psychopharmacol Section Abstract Doc Link 9690701 Disease Relevance 0 Pain Relevance 0.18
Appetite suppressant drugs as inhibitors of human cytochromes P450: in vitro inhibition of P450-2D6 by D- and L-fenfluramine, but not phentermine.
Negative_regulation (inhibition) of P450-2D6
19) Confidence 0.59 Published 1998 Journal J Clin Psychopharmacol Section Title Doc Link 9690701 Disease Relevance 0 Pain Relevance 0.16
Zuclopentixol is an alpha 1-receptor blocker and paroxetine inhibits the hepatic enzyme P450-2D6 required for conversion of the two substances.
Negative_regulation (inhibits) of P450-2D6
20) Confidence 0.59 Published 1999 Journal Ned Tijdschr Geneeskd Section Abstract Doc Link 10086144 Disease Relevance 0.76 Pain Relevance 0.12

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