INT110638

Context Info Confidence 0.59 First Reported 2003 Last Reported 2010 Negated 0 Speculated 0 Reported most in Body Documents 43 Total Number 45 Disease Relevance 21.03 Pain Relevance 21.05

cytosol (COMT) mitochondrion (COMT) small molecule metabolic process (COMT) plasma membrane (COMT) cytoplasm (COMT)

Anatomy Link Frequency Leukocyte 2 astrocytes 2 erythrocytes 1 liver 1 lymphocyte 1 COMT (Homo sapiens)

Pain Link Frequency Relevance Heat Catechol-O-methyltransferase 3043 100.00 Morphine 35 99.98 agonist 319 99.96 Dopamine 345 99.78 Pain 613 99.56 Catecholamine 139 99.56 Lasting pain 31 99.20 monoamine 8 99.20 Neurotransmitter 17 98.76 cytokine 123 98.72

Disease Link Frequency Relevance Heat Cognitive Disorder 143 99.76 Pain 606 99.56 Hantavirus Infection 860 99.48 Anaplastic Astrocytoma 128 99.36 Necrosis 32 99.32 Schizophrenia 71 99.24 Cancer 70 98.96 Facial Pain 32 98.64 Acute Liver Failure 5 97.56 Dyskinesias 337 95.84

Sentences Mentioned In

Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

In the present paper, we discuss the relevance of these studies for the treatment of Parkinson's disease (PD) on the basis of three examples: the L-DOPA ( L-3,4-dihydroxyphenylalanine, levodopa) story; the development of selegiline as a palliative and neuroprotective drug; and the safety concerns regarding tolcapone, an inhibitor of central and peripheral catechol-O-methyltransferase (COMT).

Negative_regulation (inhibitor) of catechol-O-methyltransferase associated with catechol-o-methyltransferase, disease and palliative

1) Confidence 0.59 Published 2003 Journal J. Neurol. Section Abstract Doc Link 12761633 Disease Relevance 0.17 Pain Relevance 0.15

In the present paper, we discuss the relevance of these studies for the treatment of Parkinson's disease (PD) on the basis of three examples: the L-DOPA ( L-3,4-dihydroxyphenylalanine, levodopa) story; the development of selegiline as a palliative and neuroprotective drug; and the safety concerns regarding tolcapone, an inhibitor of central and peripheral catechol-O-methyltransferase (COMT).

Negative_regulation (inhibitor) of COMT associated with catechol-o-methyltransferase, disease and palliative

2) Confidence 0.59 Published 2003 Journal J. Neurol. Section Abstract Doc Link 12761633 Disease Relevance 0.17 Pain Relevance 0.15

In contrast to compensatory SNPs, the existence of neutral SNPs in APS and/or HPS haplotypes would indicate positive selection for haplotypes associated with reduced COMT activity.

Negative_regulation (reduced) of COMT associated with catechol-o-methyltransferase and hantavirus infection

3) Confidence 0.59 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2664927 Disease Relevance 0.32 Pain Relevance 0.31

Studies show that reduced COMT activity results in increased pain sensitivity and proinflammatory cytokine production in animal models [22], [23].

Negative_regulation (reduced) of COMT associated with pain, catechol-o-methyltransferase and cytokine

4) Confidence 0.59 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2664927 Disease Relevance 1.42 Pain Relevance 1.01

The distribution of minor SNPs exclusively within haplotypes coding for reduced COMT activity may suggest different evolutionary models (e.g., enrichment for functional compensatory mutations or positive selection leading to carrying of neutral mutations) depending on the functional contribution of these SNPs.

Negative_regulation (reduced) of COMT associated with catechol-o-methyltransferase

5) Confidence 0.59 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2664927 Disease Relevance 0.23 Pain Relevance 0.32

The catechol-O-methyltransferase (COMT) val(158)met polymorphism, which codes for the substitution of valine (val) by methionine (met) leading to a reduced COMT activity in homo- or heterozygous individuals, is associated with individual pain sensitivity and dopaminergic responses in Parkinson's disease as well as with various chronic painful diseases.

Negative_regulation (reduced) of COMT associated with pain, catechol-o-methyltransferase and disease

6) Confidence 0.58 Published 2010 Journal Neurosci. Lett. Section Abstract Doc Link 20184941 Disease Relevance 0.64 Pain Relevance 0.49

For these patients, therapeutic strategies aimed at achieving steadier levodopa levels, such as controlled-release levodopa, narrowing levodopa dosing intervals, or adding a COMT inhibitor, should be helpful in reducing fluctuations in mood.

Negative_regulation (inhibitor) of COMT

7) Confidence 0.51 Published 2005 Journal Neuropsychiatric Disease and Treatment Section Body Doc Link PMC2416757 Disease Relevance 0.12 Pain Relevance 0.08

Homocysteine is a precursor for the biosynthesis of S-adenosyl-L-homocysteine (SAH) which is a strong, noncompetitive inhibitor of COMT.

Negative_regulation (inhibitor) of COMT associated with catechol-o-methyltransferase

8) Confidence 0.51 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2664927 Disease Relevance 0.84 Pain Relevance 0.26

20-fold reduction in COMT activity that is due to the longer more stable local stem-loop structure in the val158 region that reduces protein translation efficiency.

Negative_regulation (reduction) of COMT in stem associated with catechol-o-methyltransferase

9) Confidence 0.51 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2664927 Disease Relevance 0.56 Pain Relevance 0.22

-mediated inhibition of P2-COMT activity (Figure 2B).

Negative_regulation (inhibition) of P2-COMT associated with catechol-o-methyltransferase

10) Confidence 0.51 Published 2009 Journal Mol Pain Section Body Doc Link PMC2662804 Disease Relevance 0.21 Pain Relevance 0.51

overexpression dramatically decreases P2-COMT activity (P < 0.01; Figure 4A).

Negative_regulation (decreases) of P2-COMT associated with catechol-o-methyltransferase

11) Confidence 0.51 Published 2009 Journal Mol Pain Section Body Doc Link PMC2662804 Disease Relevance 0.12 Pain Relevance 0.32

-dependent suppression of P2-COMT activity.

Negative_regulation (suppression) of P2-COMT associated with catechol-o-methyltransferase

12) Confidence 0.51 Published 2009 Journal Mol Pain Section Body Doc Link PMC2662804 Disease Relevance 0.06 Pain Relevance 0.26

-dependent COMT downregulation was indeed mediated by the NF-?

Negative_regulation (downregulation) of COMT associated with catechol-o-methyltransferase

13) Confidence 0.51 Published 2009 Journal Mol Pain Section Body Doc Link PMC2662804 Disease Relevance 0.41 Pain Relevance 0.48

treatment decreased P2-COMT activity in time-dependent manner.

Negative_regulation (decreased) of P2-COMT associated with catechol-o-methyltransferase

14) Confidence 0.51 Published 2009 Journal Mol Pain Section Body Doc Link PMC2662804 Disease Relevance 0.10 Pain Relevance 0.63

-dependent inhibition of P2-COMT activity in H4 astroglioma cells.

Negative_regulation (inhibition) of P2-COMT associated with anaplastic astrocytoma and catechol-o-methyltransferase

15) Confidence 0.51 Published 2009 Journal Mol Pain Section Body Doc Link PMC2662804 Disease Relevance 0.49 Pain Relevance 0.37

Myofacial pain patients exhibit lower COMT activity relative to controls [7], and COMT inhibition increases pain sensitivity in rodents by promoting catecholamine stimulation of ?

Negative_regulation (inhibition) of COMT associated with pain, catechol-o-methyltransferase, catecholamine and face pain

16) Confidence 0.51 Published 2009 Journal Mol Pain Section Body Doc Link PMC2662804 Disease Relevance 0.37 Pain Relevance 1.08

It inhibits by 65% the COMT activity in human erythrocytes after a dose of 200 mg.

Negative_regulation (inhibits) of COMT in erythrocytes associated with catechol-o-methyltransferase

17) Confidence 0.47 Published 2010 Journal Core Evidence Section Body Doc Link PMC2915499 Disease Relevance 0.17 Pain Relevance 0.31

While there is no evidence, to date, of greater sequence variation in the COMT locus than that expected under a neutral model [54], the distribution of minor SNPs exclusively within haplotypes associated with reduced COMT activity requires further study.

Negative_regulation (reduced) of COMT associated with catechol-o-methyltransferase

18) Confidence 0.43 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2664927 Disease Relevance 0.69 Pain Relevance 0.56

downregulates COMT mRNA and protein in astrocytes.

Negative_regulation (downregulates) of COMT in astrocytes associated with catechol-o-methyltransferase

19) Confidence 0.43 Published 2009 Journal Mol Pain Section Abstract Doc Link PMC2662804 Disease Relevance 0.65 Pain Relevance 0.95

inhibits P2-COMT activity in astrocytes by inducing NF-?

Negative_regulation (inhibits) of P2-COMT in astrocytes associated with catechol-o-methyltransferase

20) Confidence 0.43 Published 2009 Journal Mol Pain Section Abstract Doc Link PMC2662804 Disease Relevance 0.58 Pain Relevance 0.91

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