INT47860

Context Info Confidence 0.57 First Reported 1993 Last Reported 2010 Negated 0 Speculated 0 Reported most in Abstract Documents 20 Total Number 20 Disease Relevance 6.06 Pain Relevance 10.00

oxidoreductase activity (Cyp1a2) endoplasmic reticulum (Cyp1a2) enzyme binding (Cyp1a2)

Anatomy Link Frequency plasma 1 liver 1 1A2 1 platelet 1 Cyp1a2 (Mus musculus)

Pain Link Frequency Relevance Heat Paracetamol 117 99.78 sSRI 20 99.64 fluoxetine 15 98.60 Endep 1 97.60 Inflammation 18 94.96 carbamazepine 3 94.80 antidepressant 10 94.40 tricyclic antidepressant 2 93.60 alcohol 11 89.92 withdrawal 1 84.04

Disease Link Frequency Relevance Heat Nicotine Addiction 67 100.00 Hepatotoxicity 32 99.90 Toxicity 22 99.74 Emergencies 3 99.26 INFLAMMATION 17 94.96 Anxiety Disorder 58 94.80 Body Weight 3 93.60 Stress 14 93.28 Adverse Drug Reaction 3 92.12 Liver Disease 18 86.20

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To determine the relative contributions of these P450's, overnight fasted male NMRI mice were pretreated with 10 ml of 50% v/w propylene glycol/kg or fluvoxamine (10 mg/kg) at -80 and -20 min. relative to acetaminophen dosing to inhibit CYP2E1 and CYP1A2, respectively.

Negative_regulation (inhibit) of CYP1A2 associated with paracetamol

1) Confidence 0.57 Published 1995 Journal Pharmacol. Toxicol. Section Abstract Doc Link 7479582 Disease Relevance 0.31 Pain Relevance 0.51

Propylene glycol inhibited the activity of CYP2E1 as indicated by 84% reduction in the clearance of 3 mg/kg dose of chlorzoxazone, whereas fluvoxamine inhibited the activity of CYP1A2 as indicated by 40% reduction in the clearance of a 10 mg/kg dose of caffeine.

Negative_regulation (inhibited) of CYP1A2

2) Confidence 0.57 Published 1995 Journal Pharmacol. Toxicol. Section Abstract Doc Link 7479582 Disease Relevance 0.32 Pain Relevance 0.54

In beta-napthaflavone-pretreated mice, CYP1A2 activity was decreased only by the high dose of APAP, and covalent binding was > 2-fold higher at the high APAP dose.

Negative_regulation (decreased) of CYP1A2 associated with paracetamol

3) Confidence 0.57 Published 1994 Journal Biochem. Biophys. Res. Commun. Section Abstract Doc Link 8074700 Disease Relevance 0.16 Pain Relevance 0.95

Loss of CYP2E1 and CYP1A2 activity as a function of acetaminophen dose: relation to toxicity.

Negative_regulation (Loss) of CYP1A2 associated with toxicity and paracetamol

4) Confidence 0.57 Published 1994 Journal Biochem. Biophys. Res. Commun. Section Title Doc Link 8074700 Disease Relevance 0.18 Pain Relevance 0.87

For example, mice lacking CYP1A2 and CYP2E1 are totally resistant to acetaminophen-induced hepatotoxicity.

Negative_regulation (lacking) of CYP1A2 associated with paracetamol and hepatotoxicity

5) Confidence 0.55 Published 2001 Journal Toxicol. Lett. Section Abstract Doc Link 11323178 Disease Relevance 0.32 Pain Relevance 0.10

Caffeine, an inhibitor of CYP1A2 activity and an enhancer of CYP3A activity, decreased APAP hepatotoxicity in wild-type mice.

Negative_regulation (inhibitor) of CYP1A2 associated with paracetamol and hepatotoxicity

6) Confidence 0.53 Published 2005 Journal Drug Metab. Dispos. Section Abstract Doc Link 16141365 Disease Relevance 0.62 Pain Relevance 1.01

Nefazodone is a weak inhibitor of cytochrome P450 (CYP) 2D6 and does not inhibit CYP1A2.

Negative_regulation (inhibit) of CYP1A2

7) Confidence 0.50 Published 1997 Journal Clin Pharmacokinet Section Abstract Doc Link 9342502 Disease Relevance 0 Pain Relevance 0.09

TAO treatment in vivo resulted in inhibition of microsomal CYP3A-catalyzed activity, measured in vitro, with no inhibition of CYP1A2 and CYP2E1 activities.

Negative_regulation (inhibition) of CYP1A2

8) Confidence 0.48 Published 2007 Journal Drug Metab. Dispos. Section Abstract Doc Link 17392391 Disease Relevance 0.34 Pain Relevance 0.82

In non-induced mice, 150 mg/kg APAP caused minimal hepatotoxicity and loss of CYP2E1- but not CYP1A2-dependent activity.

Negative_regulation (loss) of CYP1A2 associated with paracetamol and hepatotoxicity

9) Confidence 0.42 Published 1994 Journal Biochem. Biophys. Res. Commun. Section Abstract Doc Link 8074700 Disease Relevance 0.17 Pain Relevance 0.81

Thus, the protection against APAP toxicity afforded by deletion of both CYP2E1 and CYP1A2 likely reflects greatly diminished production of the toxic electrophile, NAPQI.

Negative_regulation (deletion) of CYP1A2 associated with toxicity and paracetamol

10) Confidence 0.42 Published 1998 Journal Toxicol. Appl. Pharmacol. Section Abstract Doc Link 9772215 Disease Relevance 0.66 Pain Relevance 0.62

In contrast, 400 mg/kg APAP was hepatotoxic and diminished both CYP2E1 and CYP1A2 activities.

Negative_regulation (diminished) of CYP1A2 associated with paracetamol

11) Confidence 0.42 Published 1994 Journal Biochem. Biophys. Res. Commun. Section Abstract Doc Link 8074700 Disease Relevance 0.17 Pain Relevance 0.90

The pretreatment regimen resulted in hepatic changes including: centrilobular localization of 3-(cysteine-S-yl)APAP protein adducts, selective down-regulation of cytochrome P4502E1 (CYP2E1) and CYP1A2 that produced the toxic metabolite, N-acetyl-p-benzoquinone imine, higher levels of reduced glutathione (GSH), centrilobular inflammation, and a fourfold increase in hepatocellular proliferation.

Negative_regulation (down-regulation) of CYP1A2 associated with paracetamol and inflammation

12) Confidence 0.40 Published 1999 Journal Hepatology Section Abstract Doc Link 9918922 Disease Relevance 0.26 Pain Relevance 0.92

Analysis of phase I detoxification genes revealed that CYP1A2 and CYP3A11 were up-regulated in wild-type mice but down-regulated in RXRalpha-deficient mice after APAP administration.

Negative_regulation (down-regulated) of CYP1A2 associated with paracetamol

13) Confidence 0.37 Published 2004 Journal Mol. Pharmacol. Section Abstract Doc Link 14978233 Disease Relevance 0.27 Pain Relevance 0.40

The polymorphism of this subtype can induce loss-of-function to a considerable extent.25)26) Because CYP1A2 affects only the first oxidative step of clopidogrel, induction of CYP1A2 by smoking may have a relatively weak impact on clopidogrel activation.25)26) Furthermore, we assessed residual platelet reactivity at least 3 days after emergency stenting, which may be related to a decrease in smoking-induced CYP1A2 activity.

Negative_regulation (decrease) of CYP1A2 in platelet associated with emergencies and nicotine addiction

14) Confidence 0.18 Published 2010 Journal Korean Circulation Journal Section Body Doc Link PMC2844977 Disease Relevance 0.96 Pain Relevance 0

In primary human hepatocytes isolated from liver with macrosteatosis, there is a 60% to 40% reduction in 7-ethoxycoumarin O-deethylation (ECOD) and testosterone oxidation with a reduction in CYP1A2, CYP2C9, CYP2E1, and CYP3A4 mRNA and their respective proteins to metabolize their specific substrate drugs [107].

Negative_regulation (reduction) of CYP1A2 in liver

15) Confidence 0.13 Published 2009 Journal PPAR Research Section Body Doc Link PMC2840373 Disease Relevance 0.93 Pain Relevance 0.10

Fluoxetine and paroxetine are potent inhibitors of CYP2D6, fluvoxamine markedly inhibits CYP1A2 and CYP2C19, while nefazodone is a potent inhibitor of CYP3A4.

Negative_regulation (inhibits) of CYP1A2 associated with fluoxetine

16) Confidence 0.10 Published 2003 Journal Fundam Clin Pharmacol Section Abstract Doc Link 14703714 Disease Relevance 0 Pain Relevance 0.39

Ciprofloxacine, an inhibitor of CYP1A2 did increase plasma levels of ropinirole when these two drugs were co-administered.

Negative_regulation (inhibitor) of CYP1A2 in plasma

17) Confidence 0.09 Published 2010 Journal Therapeutics and Clinical Risk Management Section Body Doc Link PMC2857615 Disease Relevance 0.06 Pain Relevance 0.04

Because of its metabolism, the clearance is moderately reduced by CYP1A2 inhibitors such as fluvoxamine and CYP2D6 inhibitors such as fluoxetine, paroxetine and bupropion, and increased by CYP1A2 inducers such as carbamazepine (deLeon et al 2005).

Negative_regulation (inhibitors) of CYP1A2 associated with carbamazepine and fluoxetine

18) Confidence 0.09 Published 2007 Journal Neuropsychiatric Disease and Treatment Section Body Doc Link PMC2656294 Disease Relevance 0.16 Pain Relevance 0.28

Fluvoxamine inhibits oxidative drug metabolizing enzymes (particularly CYP1A2, and less potently, CYP3A4 and CYP2D6) and has the potential for clinically significant drug interactions.2 In the management of OCD, an array of different augmentation strategies may be employed in patients who exhibit only partial response to selective SRIs, including the use of clomipramine or of atypical antipsychotics as an add-on therapy.5 Clinicians should take into account the fact that fluvoxamine may lead to increased plasma levels of the augmentation drugs, either by inhibiting the CYP 1A2 (ie, haloperidol, olanzapine, and clomipramine) or the CYP3A4 (ie, haloperidol, pimozide, risperidone, quetiapine, and clomipramine).

Negative_regulation (inhibits) of CYP1A2 in 1A2 associated with anxiety disorder

19) Confidence 0.05 Published 2009 Journal Neuropsychiatric Disease and Treatment Section Body Doc Link PMC2699655 Disease Relevance 0.17 Pain Relevance 0

Fluvoxamine is the only SSRI that is a potent inhibitor of cytochrome P4501A2 and hence causes serious pharmacokinetic interactions with amitriptyline, clomipramine, imipramine, theophylline, and presumably caffeine and other drugs which are metabolized by the isozyme.

Negative_regulation (inhibitor) of cytochrome P4501A2 associated with endep and ssri

20) Confidence 0.02 Published 1993 Journal Clin Investig Section Abstract Doc Link 8124052 Disease Relevance 0 Pain Relevance 0.65

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