INT1375

Context Info Confidence 0.57 First Reported 1976 Last Reported 2010 Negated 0 Speculated 0 Reported most in Abstract Documents 13 Total Number 14 Disease Relevance 5.54 Pain Relevance 4.63

Anatomy Link Frequency macrophages 1 Spina 1 smooth muscle 1 brain 1 central nervous system 1 Pde4dl1 (Rattus norvegicus)

Pain Link Frequency Relevance Heat Restless leg syndrome 9 99.92 adenocard 7 99.92 Central nervous system 5 99.68 Clonidine 18 99.60 agonist 23 99.52 antagonist 36 99.32 potassium channel 4 97.68 Abstinence syndrome 3 95.68 opiate 4 95.36 Angina 4 93.92

Disease Link Frequency Relevance Heat Increased Venous Pressure Under Development 19 99.92 Appetite Loss 38 99.90 Aging 7 99.72 Hypotension 21 98.72 Necrosis 3 98.10 Syndrome 3 95.68 Erectile Dysfunction 123 95.36 Cv General 3 Under Development 4 93.92 Peripheral Arterial Disease 1 92.28 Pulmonary Disease 165 87.36

Sentences Mentioned In

Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

Dysregulation of ghrelin secretion and ghrelin resistance in the appetite control system occurred in aged mice and that rikkunshito ameliorated aging-anorexia via inhibition of PDE3.

Negative_regulation (inhibition) of PDE3 associated with appetite loss and aging

1) Confidence 0.57 Published 2010 Journal International Journal of Peptides Section Body Doc Link PMC2915625 Disease Relevance 0.83 Pain Relevance 0.03

In rat brain homogenate, these xanthines inhibit cyclic AMP phosphodiesterase.

Negative_regulation (inhibit) of cyclic AMP phosphodiesterase in brain

2) Confidence 0.55 Published 1976 Journal Adv. Biochem. Psychopharmacol. Section Abstract Doc Link 192053 Disease Relevance 0.24 Pain Relevance 1.03

In order to study the mode of action of flavoxate, the following activities were investigated: calcium blocking, inhibition of cyclic AMP phosphodiesterase (PDE), local anaesthetic activity, the effects on the synthesis and release of prostaglandins.

Negative_regulation (inhibition) of cyclic AMP phosphodiesterase

3) Confidence 0.46 Published 1984 Journal Arch Int Pharmacodyn Ther Section Abstract Doc Link 6329116 Disease Relevance 0 Pain Relevance 0

The antispasmodic activity of a drug can be correlated with inhibition of cyclic AMP phosphodiesterase, and since papaverine is a potent PDE inhibitor, we tested flavoxate for this activity.

Negative_regulation (inhibition) of cyclic AMP phosphodiesterase

4) Confidence 0.46 Published 1984 Journal Arch Int Pharmacodyn Ther Section Abstract Doc Link 6329116 Disease Relevance 0 Pain Relevance 0.07

Moreover, rikkunshito is also an enhancement of ghrelin receptor reactivity via PDE3 inhibition.

Negative_regulation (inhibition) of PDE3

5) Confidence 0.42 Published 2010 Journal International Journal of Peptides Section Body Doc Link PMC2915625 Disease Relevance 0.75 Pain Relevance 0.03

Dihydropyridine Ca-antagonists like nicardipine are also potent inhibitor of cyclic AMP phosphodiesterase.

Negative_regulation (inhibitor) of cyclic AMP phosphodiesterase associated with antagonist

6) Confidence 0.27 Published 1987 Journal Tohoku J. Exp. Med. Section Abstract Doc Link 3576611 Disease Relevance 0.35 Pain Relevance 0.69

Since IBMX mimicked the effect of nicardipine, the effect of a low dose of i.c.v. nicardipine in attenuating the hypotensive and bradycardic effects of i.c.v. clonidine may be mediated by inhibition of cyclic AMP phosphodiesterase in the central nervous system.

Negative_regulation (inhibition) of cyclic AMP phosphodiesterase in central nervous system associated with hypotension, central nervous system and clonidine

7) Confidence 0.27 Published 1987 Journal Tohoku J. Exp. Med. Section Abstract Doc Link 3576611 Disease Relevance 0.31 Pain Relevance 0.60

Nicardipine, in a dose of 0.3 microgram/kg/min for 60 min i.v., did not modulate the hypotensive and bradycardic effects of i.c.v. clonidine. 3-Isobutyl-l-methylxanthine (IBMX), a cyclic AMP phosphodiesterase inhibitor, in a dose of 3 micrograms/kg/min for 60 min i.c.v., also attenuated the hypotensive and bradycardic effects of i.c.v. clonidine.

Negative_regulation (inhibitor) of cyclic AMP phosphodiesterase associated with hypotension and clonidine

8) Confidence 0.27 Published 1987 Journal Tohoku J. Exp. Med. Section Abstract Doc Link 3576611 Disease Relevance 0.44 Pain Relevance 0.75

Furthermore, PASMC receiving the combination of a PDE3 and a PDE4 inhibitor exhibited a significant additive or synergistic anti-mitogenic effect as compared to each PDE inhibitor used on its own.

Negative_regulation (inhibitor) of PDE3

9) Confidence 0.25 Published 2005 Journal Respir Res Section Body Doc Link PMC1291406 Disease Relevance 0.21 Pain Relevance 0

NT-702 selectively inhibited PDE3 (IC(50)=0.179 and 0.260 nM for PDE3A and 3B) more potently than cilostazol (IC(50)=231 and 237 nM for PDE3A and 3B) among recombinant human PDE1 to PDE6.

Negative_regulation (inhibited) of PDE3 associated with restless leg syndrome

10) Confidence 0.23 Published 2007 Journal Life Sci. Section Abstract Doc Link 17850826 Disease Relevance 0.80 Pain Relevance 0.74

Administered as an intracorporal injection, papaverine is a non-selective inhibitor of PDE3 and its isoforms (Carson 2007).

Negative_regulation (inhibitor) of PDE3

11) Confidence 0.14 Published 2008 Journal Therapeutics and Clinical Risk Management Section Body Doc Link PMC2643112 Disease Relevance 0.53 Pain Relevance 0.13

However, PDE4 inhibitors only weakly suppressed spontaneously generated tone, or contractions of isolated human airways smooth muscle in response to allergen, LTC4, and histamine, although this functional antagonism is significant when combined with a PDE3 inhibitor (Schmidt et al 2000).

Negative_regulation (inhibitor) of PDE3 in smooth muscle

12) Confidence 0.14 Published 2007 Journal International Journal of Chronic Obstructive Pulmonary Disease Section Body Doc Link PMC2695611 Disease Relevance 0.33 Pain Relevance 0.13

Arteriopathy is a condition associated with arterial necrosis and has been observed in rats after treatment with large doses of many vasodilators including PDE3 and PDE4 inhibitors, adenosine agonists, endothelin receptor antagonists and potassium channel openers (Spina 2004).

Negative_regulation (inhibitors) of PDE3 in Spina associated with necrosis, adenocard, antagonist, agonist and potassium channel

13) Confidence 0.14 Published 2007 Journal International Journal of Chronic Obstructive Pulmonary Disease Section Body Doc Link PMC2695611 Disease Relevance 0.21 Pain Relevance 0.23

Whilst macrophages do express PDE4 it appears that their function is poorly inhibited by PDE4 inhibitors, although the efficacy of these drugs is enhanced when used in combination with agents that raise intracellular levels of cyclic AMP (eg, prostaglandin E2) or if there is concurrent inhibition of PDE3 and PDE7 (Hatzelmann and Schudt 2001; Smith et al 2004).

Negative_regulation (inhibition) of PDE3 in macrophages

14) Confidence 0.14 Published 2007 Journal International Journal of Chronic Obstructive Pulmonary Disease Section Body Doc Link PMC2695611 Disease Relevance 0.55 Pain Relevance 0.20

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