INT157282

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Context Info
Confidence 0.75
First Reported 2009
Last Reported 2010
Negated 1
Speculated 0
Reported most in Body
Documents 5
Total Number 5
Disease Relevance 0.54
Pain Relevance 0.76

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

small molecule metabolic process (CYP1A2) oxidoreductase activity (CYP1A2) endoplasmic reticulum (CYP1A2)
enzyme binding (CYP1A2)
Anatomy Link Frequency
MT2 1
liver 1
1A2 1
CYP1A2 (Homo sapiens)
Pain Link Frequency Relevance Heat
Duloxetine 33 100.00 Very High Very High Very High
agonist 27 80.88 Quite High
opioid receptor 1 68.56 Quite High
carbamazepine 3 67.16 Quite High
Serotonin 46 66.12 Quite High
Analgesic 1 63.92 Quite High
Potency 5 63.08 Quite High
noradrenaline 26 61.08 Quite High
Nicotine 3 59.44 Quite High
Bioavailability 9 52.08 Quite High
Disease Link Frequency Relevance Heat
Nicotine Addiction 5 98.46 Very High Very High Very High
Hepatotoxicity 3 76.32 Quite High
Schizophrenia 37 76.16 Quite High
Psychosis 12 71.40 Quite High
Sleep Initiation And Maintenance Disorders 24 50.00 Quite Low
Depression 53 48.60 Quite Low
Reprotox - General 1 1 34.96 Quite Low
Reprotox - General 2 6 34.08 Quite Low
Vomiting 9 30.28 Quite Low
Liver Disease 1 30.08 Quite Low

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
Some of the mutations of CYP1A2 have been found to alter the clearance of drugs that are extensively metabolized by CYP1A2.
Localization (metabolized) of CYP1A2
1) Confidence 0.75 Published 2009 Journal Curr. Med. Chem. Section Abstract Doc Link 19754423 Disease Relevance 0 Pain Relevance 0.03
Extensive metabolism, predominantly via CYP1A2, to a lesser extent via CYP2D6, and at a very low rate via CYP2C9,151,152 has been reported, but the metabolites have no significant activity.153 Duloxetine is a moderate CYP2D6 inhibitor and may inhibit its own metabolism154,155 as well as the metabolism of CYP2D6 substrates, such as desimipramine.90,195 The inhibition or induction of CYP1A2 is not clinically important, and coadministration of duloxetine with CYP1A2 substrates does not necessitate their dose adjustment.193 However, potent inhibitors of CYP2D6 and CYP1A2 may result in enhanced duloxetine concentrations and a need for dose adjustment.191,193
Localization (duloxetine) of CYP1A2 associated with duloxetine
2) Confidence 0.63 Published 2010 Journal Neuropsychiatric Disease and Treatment Section Body Doc Link PMC2938284 Disease Relevance 0 Pain Relevance 0.60
Melatonin itself has different affinities to human MT1 and MT2 receptors (Ki = 80.7 and 383 pM, respectively).21,47 Its physiological half-life in the circulation is, as mentioned, usually less than half an hour, mainly because of rapid hepatic 6-hydroxylation by cytochrome P450 monooxygenase subforms, in particular, CYP1A2, but also CYP1A1 and CYP1B1.48,49 6-Hydroxymelatonin is conjugated and excreted.
Localization (excreted) of CYP1A2 in MT2
3) Confidence 0.40 Published 2009 Journal Neuropsychiatric Disease and Treatment Section Body Doc Link PMC2699659 Disease Relevance 0 Pain Relevance 0.07
Studies with recombinant cytochrome P450s (P450s), correlation analysis using a panel of human liver microsomes as well as immunoinhibition with anti-P450 antibodies collectively suggested that human liver microsomal P450 1A2 preferentially metabolized M-5 to predominantly M-23OH.
Localization (metabolized) of P450 1A2 in 1A2
4) Confidence 0.33 Published 2009 Journal Chem. Res. Toxicol. Section Abstract Doc Link 19138062 Disease Relevance 0.08 Pain Relevance 0.06
This suggests it is unlikely to interact with drugs that inhibit or induce these enzymes.33 Also, smoking should not affect its pharmacokinetics, like most antipsychotics except the CYP1A2 substrates clozapine and olanzapine whose clearance is affected by cigarette smoking and drugs that induce or inhibit CYP1A2.21 In vitro studies in human liver microsomes showed that iloperidone do not induce CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP3A4 and CYP3A5.33

Efficacy

Neg (except) Localization (clozapine) of CYP1A2 in liver associated with nicotine addiction
5) Confidence 0.32 Published 2010 Journal Drug design, development and therapy Section Body Doc Link PMC2846148 Disease Relevance 0.47 Pain Relevance 0

General Comments

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