INT321907

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Context Info
Confidence 0.51
First Reported 2010
Last Reported 2010
Negated 0
Speculated 1
Reported most in Body
Documents 1
Total Number 26
Disease Relevance 9.08
Pain Relevance 7.07

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 (DAO) oxidoreductase activity (DAO) peroxisome (DAO)
cellular nitrogen compound metabolic process (DAO)
Anatomy Link Frequency
brain 5
plasma 1
DAO (Homo sapiens)
Pain Link Frequency Relevance Heat
Bioavailability 78 99.50 Very High Very High Very High
Pain 208 99.44 Very High Very High Very High
Neuropathic pain 26 98.24 Very High Very High Very High
Analgesic 78 98.08 Very High Very High Very High
nMDA receptor 416 97.28 Very High Very High Very High
Lasting pain 26 95.76 Very High Very High Very High
Potency 26 94.44 High High
nMDA receptor antagonist 78 93.56 High High
Anterior cingulate 26 93.24 High High
agonist 234 89.88 High High
Disease Link Frequency Relevance Heat
Pain 182 99.44 Very High Very High Very High
Schizophrenia 572 99.24 Very High Very High Very High
Disease 78 98.92 Very High Very High Very High
Neuropathic Pain 26 98.24 Very High Very High Very High
Cognitive Disorder 338 98.16 Very High Very High Very High
Nociception 52 98.08 Very High Very High Very High
Psychosis 78 97.66 Very High Very High Very High
Nephrotoxicity 26 94.92 High High
Sprains And Strains 52 89.60 High High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
No structure activity information was described however this compound was found to be a moderately potent (IC50 = 0.9┬ÁM) inhibitor of human DAAO activity in vitro.
Negative_regulation (inhibitor) of DAAO
1) Confidence 0.51 Published 2010 Journal The Open Medicinal Chemistry Journal Section Body Doc Link PMC2905773 Disease Relevance 0.19 Pain Relevance 0.08
However, doses of (4) that inhibited DAAO activity in kidney by ~80% and in brain by ~65% failed to markedly increase cortical levels of D-serine.
Negative_regulation (inhibited) of DAAO in brain
2) Confidence 0.51 Published 2010 Journal The Open Medicinal Chemistry Journal Section Body Doc Link PMC2905773 Disease Relevance 0 Pain Relevance 0.11
Unfortunately it is not known whether the effects of CBIO or compound (4) on elevating D-serine levels following D-serine administration are due to inhibition of DAAO in the periphery, brain or most likely both compartments.
Spec (likely) Negative_regulation (inhibition) of DAAO in brain
3) Confidence 0.44 Published 2010 Journal The Open Medicinal Chemistry Journal Section Body Doc Link PMC2905773 Disease Relevance 0.20 Pain Relevance 0
Subcutaneous administration of (3) in mice dose dependently increased cerebellar D-serine concentration 2-6 fold above control values 4 h after dosing although it is not clear if this increase of brain D-serine is due to central and / or peripheral DAAO inhibition.
Negative_regulation (inhibition) of DAAO in brain
4) Confidence 0.44 Published 2010 Journal The Open Medicinal Chemistry Journal Section Body Doc Link PMC2905773 Disease Relevance 0 Pain Relevance 0.14
Collectively, the limited experience with a small number of structurally diverse inhibitors indicates that extensive inhibition of peripheral and central DAAO has a limited effect on brain or extracellular D-serine concentration.
Negative_regulation (inhibition) of DAAO in brain
5) Confidence 0.44 Published 2010 Journal The Open Medicinal Chemistry Journal Section Body Doc Link PMC2905773 Disease Relevance 0 Pain Relevance 0
High affinity D-amino acid reuptake sites could keep extracellular D-serine concentrations low even when DAAO activity is inhibited.
Negative_regulation (inhibited) of DAAO
6) Confidence 0.44 Published 2010 Journal The Open Medicinal Chemistry Journal Section Body Doc Link PMC2905773 Disease Relevance 0.05 Pain Relevance 0
Nevertheless, these findings suggest that DAAO inhibitors could be useful clinically for reducing the dose of D-serine necessary to improve psychosis or cognitive deficits associated with schizophrenia.
Negative_regulation (inhibitors) of DAAO associated with cognitive disorder, psychosis and schizophrenia
7) Confidence 0.44 Published 2010 Journal The Open Medicinal Chemistry Journal Section Body Doc Link PMC2905773 Disease Relevance 0.43 Pain Relevance 0.06
Indeed, Wake et al (2001) showed that a mutant mouse lacking DAAO activity is supersensitive to formalin-induced nociception [37].
Negative_regulation (lacking) of DAAO associated with nociception
8) Confidence 0.37 Published 2010 Journal The Open Medicinal Chemistry Journal Section Body Doc Link PMC2905773 Disease Relevance 0.81 Pain Relevance 1.11
Relatively few of the published studies have related efficacy (or lack thereof) to the extent of peripheral / brain DAAO inhibition or have demonstrated an increase of brain extracellular D-serine following a behaviorally effective dose of an inhibitor.
Negative_regulation (inhibition) of DAAO in brain
9) Confidence 0.33 Published 2010 Journal The Open Medicinal Chemistry Journal Section Body Doc Link PMC2905773 Disease Relevance 0.50 Pain Relevance 0.39
As a result, the co-administration of DAAO inhibitors with D-serine could ameliorate some of the side effects associated with the administration of high doses of D-serine, such as nephrotoxicity [49].


Negative_regulation (inhibitors) of DAAO associated with nephrotoxicity
10) Confidence 0.33 Published 2010 Journal The Open Medicinal Chemistry Journal Section Body Doc Link PMC2905773 Disease Relevance 0.59 Pain Relevance 0.20
This article highlights and reviews research advances for DAAO inhibitors published in peer reviewed journals.



Negative_regulation (inhibitors) of DAAO
11) Confidence 0.33 Published 2010 Journal The Open Medicinal Chemistry Journal Section Abstract Doc Link PMC2905773 Disease Relevance 0.56 Pain Relevance 0.07
Interestingly, preclinical studies have provided data that combining a DAAO inhibitor with D-serine may be more effective in terms of antipsychotic like activity, however, a clinically acceptable strategy for this combination remains to be determined.



Negative_regulation (inhibitor) of DAAO
12) Confidence 0.33 Published 2010 Journal The Open Medicinal Chemistry Journal Section Body Doc Link PMC2905773 Disease Relevance 0.31 Pain Relevance 0.26
The properties of (4) were further described by Smith et al. 2009 to have good rat pharmacokinetics including oral bioavailability and to dose-dependently inhibit kidney and brain (cerebellum) DAAO activity with an associated increase of plasma D-serine [42].
Negative_regulation (inhibit) of DAAO in plasma associated with bioavailability
13) Confidence 0.33 Published 2010 Journal The Open Medicinal Chemistry Journal Section Body Doc Link PMC2905773 Disease Relevance 0 Pain Relevance 0.14
Ferraris et al. 2008 described a series of compounds based on a benzo[d]isoxazol-3-ol core structure as moderately potent, competitive (with respect to D-serine) inhibitors of DAAO [43].
Negative_regulation (inhibitors) of DAAO
14) Confidence 0.33 Published 2010 Journal The Open Medicinal Chemistry Journal Section Body Doc Link PMC2905773 Disease Relevance 0 Pain Relevance 0.07
Several research reports have been published that describe the synthesis and biological effects of novel, selective, small molecule inhibitors of DAAO.
Negative_regulation (inhibitors) of DAAO
15) Confidence 0.33 Published 2010 Journal The Open Medicinal Chemistry Journal Section Abstract Doc Link PMC2905773 Disease Relevance 0.65 Pain Relevance 0.08
These inconsistent findings highlight the need for more studies to address the potential of DAAO inhibitors for treating pain.
Negative_regulation (inhibitors) of DAAO associated with pain
16) Confidence 0.33 Published 2010 Journal The Open Medicinal Chemistry Journal Section Body Doc Link PMC2905773 Disease Relevance 0.80 Pain Relevance 0.91
The therapeutic potential of DAAO inhibitors is relatively unexplored and studies have primarily addressed their value for pharmacotherapy in the treatment of positive, negative and cognitive symptoms of schizophrenia.
Negative_regulation (inhibitors) of DAAO associated with cognitive disorder and schizophrenia
17) Confidence 0.33 Published 2010 Journal The Open Medicinal Chemistry Journal Section Body Doc Link PMC2905773 Disease Relevance 0.76 Pain Relevance 0.73
However, the few published studies characterizing novel DAAO inhibitors have yielded conflicting results.
Negative_regulation (inhibitors) of DAAO
18) Confidence 0.33 Published 2010 Journal The Open Medicinal Chemistry Journal Section Body Doc Link PMC2905773 Disease Relevance 0.70 Pain Relevance 0.58
These findings suggest that the increase in D-serine needed for these behavioral effects is much greater than can be achieved by DAAO inhibition, at least by a single dose of compound (4).
Negative_regulation (inhibition) of DAAO
19) Confidence 0.33 Published 2010 Journal The Open Medicinal Chemistry Journal Section Body Doc Link PMC2905773 Disease Relevance 0.24 Pain Relevance 0.16
Because NMDA receptor dysfunction is thought to be involved in the positive (psychotic), negative and cognitive symptoms in schizophrenia, there has been much interest in developing potent and selective DAAO inhibitors for the treatment of this disease.
Negative_regulation (inhibitors) of DAAO associated with cognitive disorder, psychosis, nmda receptor, disease and schizophrenia
20) Confidence 0.33 Published 2010 Journal The Open Medicinal Chemistry Journal Section Abstract Doc Link PMC2905773 Disease Relevance 0.69 Pain Relevance 0.09

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