INT68347

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Context Info
Confidence 0.58
First Reported 1997
Last Reported 2011
Negated 1
Speculated 1
Reported most in Body
Documents 34
Total Number 38
Disease Relevance 7.62
Pain Relevance 18.35

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

mitochondrion (Cyp2d4) oxidoreductase activity (Cyp2d4) endoplasmic reticulum (Cyp2d4)
cellular_component (Cyp2d4) cytoplasm (Cyp2d4)
Anatomy Link Frequency
plasma 2
blood 1
liver 1
hepatocytes 1
Cyp2d4 (Rattus norvegicus)
Pain Link Frequency Relevance Heat
antidepressant 235 100.00 Very High Very High Very High
Analgesic 180 100.00 Very High Very High Very High
Codeine 43 100.00 Very High Very High Very High
antiarrhythmic agent 5 100.00 Very High Very High Very High
fluoxetine 202 99.96 Very High Very High Very High
Dextromethorphan 154 99.86 Very High Very High Very High
Duloxetine 259 99.70 Very High Very High Very High
sSRI 326 99.66 Very High Very High Very High
Oxycodone 277 98.48 Very High Very High Very High
addiction 8 98.24 Very High Very High Very High
Disease Link Frequency Relevance Heat
Autoimmune Hepatitis 676 99.04 Very High Very High Very High
Drug Dependence 11 98.44 Very High Very High Very High
Toxicity 38 98.00 Very High Very High Very High
Neuropathic Pain 62 96.96 Very High Very High Very High
Depression 503 96.68 Very High Very High Very High
Renal Disease 10 91.16 High High
Injury 30 90.96 High High
Sleep Disorders 115 87.84 High High
Disorders Of Creatine Metabolism 6 87.52 High High
Reprotox - General 2 38 87.32 High High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
Cimetidine is a specific CYP2D6 inhibitor [19]; hence, it was chosen to compare the inhibitory activities with Flos carthami, and the result showed that the dextromethorphan metabolic rate of 30?
Negative_regulation (inhibitor) of CYP2D6 associated with dextromethorphan
1) Confidence 0.58 Published 2011 Journal Evidence-based Complementary and Alternative Medicine : eCAM Section Body Doc Link PMC2994065 Disease Relevance 0.21 Pain Relevance 0.25
The current study provides strong evidence that the inhibition of CYP2D6 by Flos carthami could result in elevated plasma concentration of coadministered drugs that are substrates of CYP2D6, which may cause adverse side effects due to the concentration of concomitantly used drugs over the limit of the toxicity threshold, especially for the drugs with narrow therapeutic windows.
Negative_regulation (inhibition) of CYP2D6 in plasma associated with toxicity
2) Confidence 0.58 Published 2011 Journal Evidence-based Complementary and Alternative Medicine : eCAM Section Body Doc Link PMC2994065 Disease Relevance 0.59 Pain Relevance 0.09
All the data have implied that Flos carthami inhibits CYP2D6.
Negative_regulation (inhibits) of CYP2D6
3) Confidence 0.58 Published 2011 Journal Evidence-based Complementary and Alternative Medicine : eCAM Section Body Doc Link PMC2994065 Disease Relevance 0 Pain Relevance 0.19
Humans that lack cytochrome P450 2D6 (CYP2D6) activity may have an altered risk of drug dependence or abuse because this enzyme is important in the metabolism of some drugs of abuse, including hydrocodone.
Negative_regulation (lack) of cytochrome P450 2D6 associated with drug dependence and addiction
4) Confidence 0.57 Published 1997 Journal J. Pharmacol. Exp. Ther. Section Abstract Doc Link 9067326 Disease Relevance 0.16 Pain Relevance 0.12
Humans that lack cytochrome P450 2D6 (CYP2D6) activity may have an altered risk of drug dependence or abuse because this enzyme is important in the metabolism of some drugs of abuse, including hydrocodone.
Negative_regulation (lack) of CYP2D6 associated with drug dependence and addiction
5) Confidence 0.57 Published 1997 Journal J. Pharmacol. Exp. Ther. Section Abstract Doc Link 9067326 Disease Relevance 0.17 Pain Relevance 0.12
This information is still lacking for some drugs, although metabolites may exhibit in vitro inhibitory potencies of similar to (paroxetine and its M2 metabolite as inhibitors of CYP2D6) or even greater than that of the parent drug (norfluoxetine is more potent than fluoxetine as an inhibitor of CYP3A3/4, and in view of the longer half-life (t1/2) of the metabolite the potential for interactions may persist for weeks after discontinuation of the parent drug).
Negative_regulation (inhibitors) of CYP2D6 associated with fluoxetine
6) Confidence 0.54 Published 1998 Journal Clin Pharmacokinet Section Abstract Doc Link 9571301 Disease Relevance 0 Pain Relevance 0.32
This enzyme has two phenotypes in the white population: 5%–10% are poor metabolizers with diminished CYP2D6 activity.
Negative_regulation (diminished) of CYP2D6
7) Confidence 0.48 Published 2006 Journal Therapeutics and Clinical Risk Management Section Body Doc Link PMC1936259 Disease Relevance 0 Pain Relevance 1.71
Duloxetine is a moderate inhibitor of the actions of CYP2D6 and requires caution when co-administering agents metabolized by that system.
Negative_regulation (inhibitor) of CYP2D6 associated with duloxetine
8) Confidence 0.46 Published 2007 Journal Vascular Health and Risk Management Section Body Doc Link PMC2350145 Disease Relevance 0.06 Pain Relevance 0.61
Inhibitors of CYP2D6
Negative_regulation (Inhibitors) of CYP2D6
9) Confidence 0.46 Published 2007 Journal Vascular Health and Risk Management Section Body Doc Link PMC2350145 Disease Relevance 0.06 Pain Relevance 0.58
Paroxetine is a moderate inhibitor of CYP2D6.
Negative_regulation (inhibitor) of CYP2D6
10) Confidence 0.46 Published 2007 Journal Vascular Health and Risk Management Section Body Doc Link PMC2350145 Disease Relevance 0.06 Pain Relevance 0.59
Several authors have suggested the concomitant administration of DM and a CYP2D6 reversible inhibitor in order to enhance the exposure of DM and limit the exposure to total dextrorphan (DX).
Negative_regulation (inhibitor) of CYP2D6 associated with dextromethorphan
11) Confidence 0.43 Published 2004 Journal J. Vet. Pharmacol. Ther. Section Abstract Doc Link 15096109 Disease Relevance 0.10 Pain Relevance 0.44
The inhibitory effect of sodium ozagrel on CYP2D6 activity was noncompetitive with dextromethorphan with a K(i) of 324.94 microM.
Negative_regulation (effect) of CYP2D6 associated with dextromethorphan
12) Confidence 0.43 Published 2007 Journal Eur. J. Pharmacol. Section Abstract Doc Link 17651725 Disease Relevance 0 Pain Relevance 0.37
All data suggested that Flos carthami inhibited the activity of CYP2D6.

3.2.

Negative_regulation (inhibited) of CYP2D6
13) Confidence 0.43 Published 2011 Journal Evidence-based Complementary and Alternative Medicine : eCAM Section Body Doc Link PMC2994065 Disease Relevance 0 Pain Relevance 0.50
This result suggested that Flos carthami could inhibit CYP2D6 activity (Figure 5).

3.4.

Negative_regulation (inhibit) of CYP2D6
14) Confidence 0.43 Published 2011 Journal Evidence-based Complementary and Alternative Medicine : eCAM Section Body Doc Link PMC2994065 Disease Relevance 0 Pain Relevance 0.23
One of the most important findings of the current study is that Flos carthami inhibits the activity of CYP2D6.
Negative_regulation (inhibits) of CYP2D6
15) Confidence 0.43 Published 2011 Journal Evidence-based Complementary and Alternative Medicine : eCAM Section Body Doc Link PMC2994065 Disease Relevance 0.10 Pain Relevance 0.19
Thus, fluvoxamine is a potent CYP1A2 and CYP2C19 inhibitor, and a moderate CYP2C9, CYP2D6, and CYP3A4 inhibitor; fluoxetine and paroxetine are potent CYP2D6 inhibitors; sertraline is a moderate CYP2D6 inhibitor; and citalopram has little effect on the major cytochrome-P450 isoforms (Hemeryck and Belpaire 2002).
Negative_regulation (inhibitors) of CYP2D6 associated with fluoxetine
16) Confidence 0.42 Published 2008 Journal Neuropsychiatric Disease and Treatment Section Body Doc Link PMC2515899 Disease Relevance 0.50 Pain Relevance 0.61
Thus, fluvoxamine is a potent CYP1A2 and CYP2C19 inhibitor, and a moderate CYP2C9, CYP2D6, and CYP3A4 inhibitor; fluoxetine and paroxetine are potent CYP2D6 inhibitors; sertraline is a moderate CYP2D6 inhibitor; and citalopram has little effect on the major cytochrome-P450 isoforms (Hemeryck and Belpaire 2002).
Negative_regulation (inhibitor) of CYP2D6 associated with fluoxetine
17) Confidence 0.42 Published 2008 Journal Neuropsychiatric Disease and Treatment Section Body Doc Link PMC2515899 Disease Relevance 0.49 Pain Relevance 0.63
Decreased CYP 2D6 activity has been associated with cardiovascular toxicity observed during treatment with venlafaxine (54).
Negative_regulation (Decreased) of CYP 2D6 associated with toxicity
18) Confidence 0.42 Published 2006 Journal International Journal of Clinical Practice Section Body Doc Link PMC1448696 Disease Relevance 0.10 Pain Relevance 0.31
About 5–10% of all Caucasians lack a functional CYP 2D6 enzyme and are phenotypically poor metabolisers (44).
Negative_regulation (lack) of CYP 2D6
19) Confidence 0.42 Published 2006 Journal International Journal of Clinical Practice Section Body Doc Link PMC1448696 Disease Relevance 0.07 Pain Relevance 0.45
Although venlafaxine is considered by some investigators to be a weak inhibitor of CYP 2D6 (43), CYP 2D6 plays an important role in the formation of O-desmethylvenlafaxine that is one of venlafaxine's major metabolites (53).
Negative_regulation (inhibitor) of CYP 2D6
20) Confidence 0.42 Published 2006 Journal International Journal of Clinical Practice Section Body Doc Link PMC1448696 Disease Relevance 0.08 Pain Relevance 0.30

General Comments

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