INT10798

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Context Info
Confidence 0.56
First Reported 1990
Last Reported 2010
Negated 6
Speculated 2
Reported most in Abstract
Documents 24
Total Number 27
Disease Relevance 5.82
Pain Relevance 11.31

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
plasma 3
respiratory 2
blood 1
lung 1
CYP2D6 (Homo sapiens)
Pain Link Frequency Relevance Heat
opioid receptor 74 100.00 Very High Very High Very High
tramadol 27 100.00 Very High Very High Very High
Morphine 213 99.98 Very High Very High Very High
Codeine 40 99.88 Very High Very High Very High
Opioid 405 99.82 Very High Very High Very High
rapifen 20 99.72 Very High Very High Very High
Antiemetics 10 99.40 Very High Very High Very High
Versed 5 99.36 Very High Very High Very High
Oxycodone 44 99.28 Very High Very High Very High
Analgesic 70 99.06 Very High Very High Very High
Disease Link Frequency Relevance Heat
Lung Cancer 11 99.84 Very High Very High Very High
Vomiting 258 99.40 Very High Very High Very High
Laryngeal Cancer 5 98.12 Very High Very High Very High
Disease 229 97.70 Very High Very High Very High
Respiratory Failure 5 97.08 Very High Very High Very High
Stress 23 96.80 Very High Very High Very High
Pain 283 96.48 Very High Very High Very High
Hepatotoxicity 10 95.80 Very High Very High Very High
Toxicity 22 95.42 Very High Very High Very High
Pressure Volume 2 Under Development 13 93.96 High High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
This may be due to the accumulation of active metabolites or differences in the phenotype for CYP2D6 that metabolizes oxycodone.
Positive_regulation (accumulation) of CYP2D6 associated with oxycodone
1) Confidence 0.56 Published 2007 Journal Therapeutics and Clinical Risk Management Section Body Doc Link PMC2386360 Disease Relevance 0.78 Pain Relevance 1.76
Spectral scanning of CYP2D6 with paroxetine yielded an increase in absorbance at 456 nm suggesting paroxetine inactivation of CYP2D6 via the formation of a metabolite intermediate complex.
Positive_regulation (inactivation) of CYP2D6
2) Confidence 0.50 Published 2003 Journal Drug Metab. Dispos. Section Abstract Doc Link 12584155 Disease Relevance 0 Pain Relevance 0.31
Considering the rather high frequencies of CYP2D6*10 and CYP2D6*17 alleles for Asians and African Americans, respectively, these data provide further insight into ethnic differences in CYP2D6-mediated drug metabolism.
Positive_regulation (frequencies) of CYP2D6
3) Confidence 0.50 Published 2007 Journal Drug Metab. Dispos. Section Abstract Doc Link 17470523 Disease Relevance 0 Pain Relevance 0.40
Considering the rather high frequencies of CYP2D6*10 and CYP2D6*17 alleles for Asians and African Americans, respectively, these data provide further insight into ethnic differences in CYP2D6-mediated drug metabolism.
Positive_regulation (frequencies) of CYP2D6
4) Confidence 0.50 Published 2007 Journal Drug Metab. Dispos. Section Abstract Doc Link 17470523 Disease Relevance 0 Pain Relevance 0.40
It has recently been shown that O-demethylation of the opioid drug codeine to morphine depends on the sparteine/debrisoquine oxygenase (CYP2D6) which in man exhibits genetic polymorphism.
Positive_regulation (depends) of CYP2D6 associated with opioid, morphine and codeine
5) Confidence 0.50 Published 1993 Journal Pain Section Abstract Doc Link 8351162 Disease Relevance 0.18 Pain Relevance 0.81
Therefore, it may be hypothesized that the final step in an endogenous synthesis of morphine from codeine also depends on CYP2D6.
Positive_regulation (depends) of CYP2D6 associated with codeine and morphine
6) Confidence 0.50 Published 1993 Journal Pain Section Abstract Doc Link 8351162 Disease Relevance 0.50 Pain Relevance 1.18
This template defines the stereochemical requirements for CYP2D6 substrates in terms of the volume occupied and positions of key atoms.
Positive_regulation (requirements) of CYP2D6
7) Confidence 0.50 Published 1991 Journal Carcinogenesis Section Abstract Doc Link 1747920 Disease Relevance 0 Pain Relevance 0
It has been shown previously that alfentanil clearance is independent of the polymorphic debrisoquine hydroxylase (P-450 2D6), and it is therefore of interest to identify the human cytochrome P-450 enzymes involved in noralfentanil formation, the primary reaction involved in the oxidative N-dealkylation at the piperidine nitrogen.
Neg (independent) Positive_regulation (independent) of P-450 2D6 associated with rapifen
8) Confidence 0.50 Published 1992 Journal Anesthesiology Section Abstract Doc Link 1519785 Disease Relevance 0 Pain Relevance 0.37
It has been shown previously that alfentanil clearance is independent of the polymorphic debrisoquine hydroxylase (P-450 2D6), and it is therefore of interest to identify the human cytochrome P-450 enzymes involved in noralfentanil formation, the primary reaction involved in the oxidative N-dealkylation at the piperidine nitrogen.
Neg (independent) Positive_regulation (independent) of polymorphic debrisoquine hydroxylase associated with rapifen
9) Confidence 0.50 Published 1992 Journal Anesthesiology Section Abstract Doc Link 1519785 Disease Relevance 0 Pain Relevance 0.37
The frequency of the mutated active CYP2D6*9 allele was increased in lung cancer patients (p < 0.01) but not in larynx cancer patients.
Neg (not) Positive_regulation (increased) of CYP2D6 in lung associated with laryngeal cancer and lung cancer
10) Confidence 0.50 Published 2001 Journal Oncology Section Abstract Doc Link 11474250 Disease Relevance 0.83 Pain Relevance 0.14
However, it is not clear whether an active CYP2D6 enzyme is required for opioid receptor-mediated effects in man after standard dihydrocodeine doses.
Spec (whether) Positive_regulation (required) of CYP2D6 enzyme associated with opioid receptor
11) Confidence 0.50 Published 2003 Journal Int J Clin Pharmacol Ther Section Abstract Doc Link 12665158 Disease Relevance 0 Pain Relevance 0.10
Tramadol is an opioid drug metabolised in phase I by cytochrome P450 (CYP) enzymes, of which CYP2D6 is mainly responsible for the O-demethylation of tramadol, but is not involved in N-demethylation.
Neg (not) Positive_regulation (involved) of CYP2D6 associated with tramadol and opioid
12) Confidence 0.49 Published 2003 Journal Forensic Sci. Int. Section Abstract Doc Link 12893130 Disease Relevance 0.09 Pain Relevance 0.72
The risk of pharmacokinetic drug-drug interactions may be low.175,219 Moreover, induction or inhibition of CYP2D6 or CYP2C19 has no significant effect on milnacipran.175
Positive_regulation (induction) of CYP2D6
13) Confidence 0.48 Published 2010 Journal Neuropsychiatric Disease and Treatment Section Body Doc Link PMC2938284 Disease Relevance 0.29 Pain Relevance 0.47
In contrast with desvenlafaxine, the CYP2D6 genetic polymorphism has a significant influence on venlafaxine pharmacokinetics.122 Both drugs may have low potential for drug interactions, because of low protein binding and a relatively weak inhibitory effect on CYP isoenzymes.90,123 Nevertheless, increased plasma levels of imipramine, its metabolite desimipramine,124 and risperidone were associated with concomitant administration of venlafaxine.125 Furthermore, diphenhydramine may alter the disposition of venlafaxine via inhibition of CYP2D6.126 CYP3A4 inducers may enhance the clearance rate of desvenlafaxine.122
Positive_regulation (inducers) of CYP2D6 in plasma
14) Confidence 0.48 Published 2010 Journal Neuropsychiatric Disease and Treatment Section Body Doc Link PMC2938284 Disease Relevance 0 Pain Relevance 0
In summary, our analyses indicate that individual polymorphisms in GSTT1 and CYP2D6 genes were significant but minor predictors of blood trihalomethane levels 10 min after showering and of the differences between blood levels 10 min after showering and those at baseline.
Positive_regulation (polymorphisms) of CYP2D6 in blood
15) Confidence 0.46 Published 2008 Journal Environ Health Perspect Section Body Doc Link PMC2199304 Disease Relevance 0.13 Pain Relevance 0
Coadministration of lopinavir/ritonavir is contraindicated with certain drugs (i.e. flecainide, propafenone, astemizole, terfenadine, ergot derivatives, cisapride, pimozide, midazolam and triazolam) that are highly dependent on CYP3A or CYP2D6 for clearance and for which elevated plasma concentrations are associated with serious and/or life-threatening events.
Positive_regulation (dependent) of CYP2D6 in plasma associated with versed
16) Confidence 0.43 Published 2003 Journal Drugs Section Abstract Doc Link 12662125 Disease Relevance 0.22 Pain Relevance 0.05
Codeine is a popular opioid prodrug dependent on the activity of the specific cytochrome P450 enzyme 2D6 (CYP2D6).
Positive_regulation (dependent) of CYP2D6 associated with opioid and codeine
17) Confidence 0.42 Published 2000 Journal Anaesth Intensive Care Section Abstract Doc Link 11153286 Disease Relevance 0 Pain Relevance 0.60
Although CYP2C9, CYP2C19 and CYP2E1 are also induced, no specific inducers of CYP2D6 have yet been identified clearly.
Neg (no) Positive_regulation (inducers) of CYP2D6
18) Confidence 0.41 Published 2008 Journal Nutr Metab (Lond) Section Body Doc Link PMC2584094 Disease Relevance 0.09 Pain Relevance 0.10
Copy number variation: CYP2A6, CYP2D6, GSTM1, GSTT1 and 1500 other such sites
Positive_regulation (variation) of CYP2D6
19) Confidence 0.39 Published 2008 Journal Eur J Clin Pharmacol Section Body Doc Link PMC2235910 Disease Relevance 0.16 Pain Relevance 0
The data suggest that citalopram and venlafaxine are least likely to effect CYP2D6 activity and that paroxetine and fluoxetine are more potent inhibitors and should be avoided35.
Spec (likely) Positive_regulation (effect) of CYP2D6 associated with fluoxetine
20) Confidence 0.37 Published 2010 Journal Current Oncology Section Body Doc Link PMC2826783 Disease Relevance 0.61 Pain Relevance 0.46

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