INT94859

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Context Info
Confidence 0.43
First Reported 2001
Last Reported 2010
Negated 0
Speculated 1
Reported most in Body
Documents 67
Total Number 69
Disease Relevance 33.66
Pain Relevance 10.28

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

cytosol (Pde5a) signal transduction (Pde5a)
Anatomy Link Frequency
nerve 3
corpus 2
plasma 1
myocardium 1
aorta 1
Pde5a (Rattus norvegicus)
Pain Link Frequency Relevance Heat
Angina 86 99.66 Very High Very High Very High
ischemia 45 99.22 Very High Very High Very High
backache 96 99.00 Very High Very High Very High
adenocard 93 98.96 Very High Very High Very High
Serotonin 60 98.90 Very High Very High Very High
Central nervous system 21 98.60 Very High Very High Very High
Brush evoked pain 6 97.12 Very High Very High Very High
anticonvulsant 2 95.98 Very High Very High Very High
depression 63 95.92 Very High Very High Very High
headache 92 95.52 Very High Very High Very High
Disease Link Frequency Relevance Heat
Erectile Dysfunction 3534 99.80 Very High Very High Very High
Cv General 3 Under Development 115 99.66 Very High Very High Very High
Increased Venous Pressure Under Development 262 99.60 Very High Very High Very High
Nervous System Injury 110 99.56 Very High Very High Very High
Reprotox - General 2 338 99.50 Very High Very High Very High
Toxicity 9 99.32 Very High Very High Very High
Cv Unclassified Under Development 207 99.22 Very High Very High Very High
Myalgia 51 99.22 Very High Very High Very High
Coronary Heart Disease 105 99.04 Very High Very High Very High
Back Pain 72 99.00 Very High Very High Very High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
Tadalafil is unique to the PDE5 inhibitors available because of its efficacy up to 36 h after dosing.
Negative_regulation (inhibitors) of PDE5
1) Confidence 0.43 Published 2006 Journal Clinical Interventions in Aging Section Body Doc Link PMC2699638 Disease Relevance 0.46 Pain Relevance 0.09
At present, inhibition of PDE5 with oral agents appears to be the treatment of choice (Kubin et al 2003).
Negative_regulation (inhibition) of PDE5
2) Confidence 0.43 Published 2006 Journal Clinical Interventions in Aging Section Body Doc Link PMC2699638 Disease Relevance 1.05 Pain Relevance 0.06
Moreover, both drugs reversed streptozotocin-induced phosphodiesterase 5A2 mRNA expression reduction.
Negative_regulation (reduction) of phosphodiesterase 5A2
3) Confidence 0.41 Published 2010 Journal Eur. J. Pharmacol. Section Abstract Doc Link 20079349 Disease Relevance 1.21 Pain Relevance 0.66
PDE-5 inhibitors could be considered as a new class of anti-nociceptive agents for future drug development.
Negative_regulation (inhibitors) of PDE-5 associated with nociception
4) Confidence 0.35 Published 2005 Journal Inflammopharmacology Section Abstract Doc Link 16280099 Disease Relevance 0.56 Pain Relevance 0.23
In accordance with this, inhibition of PDE-5A in rat myocardium probably underlies the cardioprotective effect of sildenafil against isoproterenol-induced cardiac hypertrophy observed in the present study.
Negative_regulation (inhibition) of PDE-5A in myocardium associated with coronary heart disease
5) Confidence 0.32 Published 2005 Journal BMC Pharmacol Section Body Doc Link PMC1131906 Disease Relevance 0.43 Pain Relevance 0.05
The present study investigated the in-vivo effect of sildenafil as a phosphodiestrase-5A (PDE-5A) inhibitor on the hypertrophic response of rat heart to isoproterenol and the relation of this effect to the level of myocardial cGMP and integrity of the constitutive nitric oxide synthase (cNOS) activity.


Spec (investigated) Negative_regulation (inhibitor) of PDE-5A in heart
6) Confidence 0.32 Published 2005 Journal BMC Pharmacol Section Abstract Doc Link PMC1131906 Disease Relevance 0.48 Pain Relevance 0
Sildenafil is a selective inhibitor of phosphodiesterase-5A (PDE-5A), the enzyme that hydrolyzes cGMP.
Negative_regulation (inhibitor) of phosphodiesterase-5A
7) Confidence 0.32 Published 2005 Journal BMC Pharmacol Section Body Doc Link PMC1131906 Disease Relevance 0.22 Pain Relevance 0
Previous studies have shown that inhibition of PDE-5A in the myocardium enhanced coronary blood flow during exercise-induced ischemia, blunted cardiac stimulation by dobutamine and reduced contractility of adrenergically stimulated papillary muscle [22-24].
Negative_regulation (inhibition) of PDE-5A in papillary muscle associated with ischemia
8) Confidence 0.32 Published 2005 Journal BMC Pharmacol Section Body Doc Link PMC1131906 Disease Relevance 0.43 Pain Relevance 0.05
Consequently, PDE-5A inhibition by sildenafil and cellular accumulation of cGMP would be the braking force against isoproterenol-induced cardiac hypertrophy found in the present study.
Negative_regulation (inhibition) of PDE-5A associated with coronary heart disease
9) Confidence 0.32 Published 2005 Journal BMC Pharmacol Section Body Doc Link PMC1131906 Disease Relevance 0.44 Pain Relevance 0.03
CONCLUSION: Celecoxib caused coronary vasodilatation in guinea-pig hearts and relaxation of rat aorta and had a potentiating effect on the NO/cGMP signaling pathway in rat aorta through specific blockade of PDE5.
Negative_regulation (blockade) of PDE5 in aorta
10) Confidence 0.32 Published 2007 Journal Cardiovasc. Res. Section Body Doc Link 17383621 Disease Relevance 0 Pain Relevance 0
Celecoxib and valdecoxib inhibited human PDE5A1 with an IC(50) of 1.6x10(-5) and 1x10(-4) M, respectively, whereas other coxibs were without inhibitory effect.
Negative_regulation (inhibited) of PDE5A1
11) Confidence 0.32 Published 2007 Journal Cardiovasc. Res. Section Body Doc Link 17383621 Disease Relevance 0 Pain Relevance 0
Celecoxib dilates guinea-pig coronaries and rat aortic rings and amplifies NO/cGMP signaling by PDE5 inhibition.
Negative_regulation (inhibition) of PDE5
12) Confidence 0.32 Published 2007 Journal Cardiovasc. Res. Section Title Doc Link 17383621 Disease Relevance 0.29 Pain Relevance 0.19
These unexpected findings clearly support the notion that celecoxib possesses an as yet undisclosed molecule-specific property that possibly compensates a decrease of prostacyclin-dependent cAMP generation by concomitantly increasing cGMP levels resulting from inhibition of PDE5.


Negative_regulation (inhibition) of PDE5
13) Confidence 0.32 Published 2007 Journal Cardiovasc. Res. Section Body Doc Link 17383621 Disease Relevance 0 Pain Relevance 0
This was supported by studies for vasorelaxation, interaction with the NO/cGMP pathway, and measurement of cyclic nucleotide amounts released from rat aortic rings, and inhibition of human PDE5 as well as PDE4 activity.
Negative_regulation (inhibition) of PDE5
14) Confidence 0.32 Published 2007 Journal Cardiovasc. Res. Section Body Doc Link 17383621 Disease Relevance 0 Pain Relevance 0
We aimed to determine which mechanism possibly accounts for the beneficial effect by investigating its vascular action in different in vitro preparations in comparison with other coxibs and reference phosphodiesterase-5 (PDE5) inhibitors.
Negative_regulation (inhibitors) of PDE5
15) Confidence 0.32 Published 2007 Journal Cardiovasc. Res. Section Abstract Doc Link 17383621 Disease Relevance 0.26 Pain Relevance 0.18
In several clinical studies for the treatment of ED, a significant greater efficacy of PDE5 inhibitors in the younger with respect to older subjects (89.1% vs 65.7%; p<0.01) has been reported (Tsujimura et al 2002).
Negative_regulation (inhibitors) of PDE5 associated with erectile dysfunction
16) Confidence 0.32 Published 2006 Journal Clinical Interventions in Aging Section Body Doc Link PMC2699638 Disease Relevance 0.36 Pain Relevance 0
Most of the side effects reported in the clinical trials are dose-dependent and consistent with the vasodilatatory effect of PDE-5 inhibition.
Negative_regulation (inhibition) of PDE-5
17) Confidence 0.32 Published 2006 Journal Clinical Interventions in Aging Section Body Doc Link PMC2699638 Disease Relevance 0.83 Pain Relevance 0.40
Back pain or myalgia or both appearing as a consequence of PDE5 inhibition was experienced by 8.3%–9.4% of men taking tadalafil 10–20 mg.
Negative_regulation (inhibition) of PDE5 associated with myalgia and backache
18) Confidence 0.32 Published 2006 Journal Clinical Interventions in Aging Section Body Doc Link PMC2699638 Disease Relevance 0.82 Pain Relevance 0.38
PDE5 inhibitors are a safe and efficacious option for most elderly patients, and now represent first-line therapy also for their socio-economic impact (Anastasiadis et al 2002).
Negative_regulation (inhibitors) of PDE5
19) Confidence 0.32 Published 2006 Journal Clinical Interventions in Aging Section Body Doc Link PMC2699638 Disease Relevance 0.98 Pain Relevance 0.05
Whether the observed changes in the hormonal pattern may be attributed to the increased sexual activity, or directly due to the PDE5 inhibition (eg, NO stimulates hypothalamic gonadotropin-releasing hormone [Kohsaka et al 1999], and inhibits PRL release in rats [Velardez et al 2000]) remains to be determined.
Negative_regulation (inhibition) of PDE5
20) Confidence 0.32 Published 2006 Journal Clinical Interventions in Aging Section Body Doc Link PMC2699638 Disease Relevance 0.46 Pain Relevance 0

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