INT39418

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Context Info
Confidence 0.57
First Reported 1983
Last Reported 2005
Negated 0
Speculated 0
Reported most in Abstract
Documents 12
Total Number 15
Disease Relevance 0.80
Pain Relevance 6.93

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

oxidoreductase activity (Tdo2)
Anatomy Link Frequency
liver 8
brain 3
forebrain 1
Tdo2 (Rattus norvegicus)
Pain Link Frequency Relevance Heat
fluoxetine 31 99.92 Very High Very High Very High
Morphine 8 99.82 Very High Very High Very High
Serotonin 13 99.46 Very High Very High Very High
depression 7 99.28 Very High Very High Very High
antidepressant 7 99.22 Very High Very High Very High
Paracetamol 14 98.40 Very High Very High Very High
aspirin 10 98.08 Very High Very High Very High
narcan 12 96.80 Very High Very High Very High
Neurotransmitter 5 95.56 Very High Very High Very High
monoamine 2 94.72 High High
Disease Link Frequency Relevance Heat
Depression 7 99.28 Very High Very High Very High
Porphyria 1 98.00 Very High Very High Very High
Suicidal Behaviour 1 91.68 High High
Stress 5 83.56 Quite High
Hepatic Porphyrias 2 42.80 Quite Low

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
We previously showed that acetaminophen administration to rats increases forebrain serotonin levels as a result of the inhibition of liver tryptophan-2,3-dioxygenase (TDO).
Negative_regulation (inhibition) of TDO in forebrain associated with paracetamol and serotonin
1) Confidence 0.57 Published 2004 Journal Metab Brain Dis Section Abstract Doc Link 15214507 Disease Relevance 0 Pain Relevance 0.83
Similar pattern of inhibition of tryptophan pyrrolase activity by fluoxetine hydrochloride in both sexes of rats.
Negative_regulation (inhibition) of pyrrolase associated with fluoxetine
2) Confidence 0.51 Published 2003 Journal Pak J Pharm Sci Section Title Doc Link 16414576 Disease Relevance 0 Pain Relevance 0.37
Despite elevated holo-enzyme form of tryptophan pyrrolase in female rats, we have found similar inhibition of tryptophan pyrrolase activity by fluoxetine hydrochloride in both male and female rats.
Negative_regulation (inhibition) of pyrrolase associated with fluoxetine
3) Confidence 0.51 Published 2003 Journal Pak J Pharm Sci Section Abstract Doc Link 16414576 Disease Relevance 0 Pain Relevance 0.44
Fluoxetine, a clinically proven antidepressant, have shown statistically significant inhibition of hepatic tryptophan pyrrolase activities (holo, total and apo form) in both the sexes of rats at 10 & 30 mg/kg doses.
Negative_regulation (inhibition) of pyrrolase associated with antidepressant and fluoxetine
4) Confidence 0.51 Published 2003 Journal Pak J Pharm Sci Section Abstract Doc Link 16414576 Disease Relevance 0 Pain Relevance 0.43
Inhibition of rat liver tryptophan pyrrolase activity by fluoxetine.
Negative_regulation (Inhibition) of pyrrolase in liver associated with fluoxetine
5) Confidence 0.51 Published 1999 Journal Pak J Pharm Sci Section Title Doc Link 16414828 Disease Relevance 0.07 Pain Relevance 0.35
The maximum inhibition of basal liver tryptophan pyrrolase activity at 2 h after administration was observed with 1 mg/kg dose for the total enzyme and apoenzyme activities and that significant inhibition of these two activities was evident with a dose of the drug as small as 0.5 mg/kg.
Negative_regulation (inhibition) of pyrrolase in liver
6) Confidence 0.51 Published 1999 Journal Pak J Pharm Sci Section Abstract Doc Link 16414828 Disease Relevance 0.07 Pain Relevance 0.31
The present study has demonstrated the effectiveness of acute administration of fluoxetine to inhibit rat liver tryptophan pyrrolase activity.
Negative_regulation (inhibit) of pyrrolase in liver associated with fluoxetine
7) Confidence 0.51 Published 1999 Journal Pak J Pharm Sci Section Abstract Doc Link 16414828 Disease Relevance 0.06 Pain Relevance 0.30
In view of the role of tryptophan depletion and thus 5-HT in pathophysiology of depression, it is strongly suggested that the inhibition of liver tryptophan pyrrolase activity may be a major mechanism of antidepressant action.
Negative_regulation (inhibition) of pyrrolase in liver associated with antidepressant and depression
8) Confidence 0.51 Published 1999 Journal Pak J Pharm Sci Section Abstract Doc Link 16414828 Disease Relevance 0.10 Pain Relevance 0.35
RESULTS: In in-vitro (10 - 1000mM) as well in-vivo (0.5-30 mg/kg body wt.) studies, fluoxetine showed a statistically significant inhibition of rat liver tryptophan pyrrolase (tryptophan-2,3-dioxygenase; EC 1.13.11.11) activity.
Negative_regulation (inhibition) of tryptophan pyrrolase in liver
9) Confidence 0.51 Published 2003 Journal J Coll Physicians Surg Pak Section Body Doc Link 12685966 Disease Relevance 0 Pain Relevance 0
CONCLUSION: It is suggested that major mechanism of action of fluoxetine is that of elevating brain tryptophan concentration and hence 5-HT synthesis by increasing the availability of circulating tryptophan to the brain secondarily to inhibition of major tryptophan degrading enzyme, hepatic tryptophan pyrrolase.
Negative_regulation (inhibition) of tryptophan pyrrolase in brain
10) Confidence 0.51 Published 2003 Journal J Coll Physicians Surg Pak Section Body Doc Link 12685966 Disease Relevance 0 Pain Relevance 0
The results show that acetaminophen alone increases brain serotonin as well as norepinephrine levels with a concomitant inhibition of liver TDO activity.
Negative_regulation (inhibition) of TDO in liver associated with paracetamol and serotonin
11) Confidence 0.50 Published 2004 Journal Metab Brain Dis Section Abstract Doc Link 15214507 Disease Relevance 0 Pain Relevance 1.08
Naloxone prevents or reverses the following effects in the rat: (a) the chronic morphine-induced increase in liver [NADPH]; (b) the consequent chronic morphine-induced inhibition of liver tryptophan pyrrolase activity; (c) the resultant chronic morphine-induced enhancement of brain 5-hydroxytryptamine synthesis; (d) the similar effects on liver and brain tryptophan metabolism exerted chronically by other drugs of dependence (ethanol, nicotine and phenobarbitone); (e) the acute ethanol-induced increase in the hepatic [NADH]/[NAD] ratio.
Negative_regulation (inhibition) of pyrrolase in liver associated with addiction, nicotine, narcan and morphine
12) Confidence 0.38 Published 1983 Journal Life Sci. Section Abstract Doc Link 6664250 Disease Relevance 0 Pain Relevance 0.99
Administration of fluoxetine-HCl (20 mg/kg) inhibited holo and total Tp pyrrolase enzyme activities when compared to saline injected rats and ultimately increases liver Tp concentrations.
Negative_regulation (inhibited) of Tp pyrrolase in liver associated with fluoxetine
13) Confidence 0.36 Published 2005 Journal Pak J Pharm Sci Section Abstract Doc Link 16380345 Disease Relevance 0.30 Pain Relevance 0.51
We have shown that this event results in marked impairment of hepatic tryptophan pyrrolase activity and consequently in elevated tryptophan content and enhanced 5-hydroxytryptamine (5-HT) turnover in the brain of such porphyric rats.
Negative_regulation (impairment) of pyrrolase in brain
14) Confidence 0.29 Published 1985 Journal J. Pharmacol. Exp. Ther. Section Abstract Doc Link 3968635 Disease Relevance 0.19 Pain Relevance 0
Naloxone prevents or reverses the following effects in the rat: (a) the chronic morphine-induced increase in liver [NADPH]; (b) the consequent chronic morphine-induced inhibition of liver tryptophan pyrrolase activity; (c) the resultant chronic morphine-induced enhancement of brain 5-hydroxytryptamine synthesis; (d) the similar effects on liver and brain tryptophan metabolism exerted chronically by other drugs of dependence (ethanol, nicotine and phenobarbitone); (e) the acute ethanol-induced increase in the hepatic [NADH]/[NAD] ratio.
Negative_regulation (inhibition) of pyrrolase in brain associated with addiction, nicotine, narcan and morphine
15) Confidence 0.13 Published 1983 Journal Life Sci. Section Abstract Doc Link 6664250 Disease Relevance 0 Pain Relevance 0.99

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