How to Trip Rapid Review

Step 1: Select articles relevant to your search (remember the system is only optimised for single intervention studies)

Step 2: press

Step 3: review the result, and maybe amend the or if you know better! If we're unsure of the overall sentiment of the trial we will display the conclusion under the article title. We then require you to tell us what the correct sentiment is.

6,556 results for

Phosphodiesterase Inhibitor

by
...
Latest & greatest
Alerts

Export results

Use check boxes to select individual results below

SmartSearch available

Trip's SmartSearch engine has discovered connected searches & results. Click to show

21. Therapeutic potential of phosphodiesterase type 5 inhibitors in heart failure with preserved ejection fraction and combined post- and pre-capillary pulmonary hypertension. (Abstract)

Therapeutic potential of phosphodiesterase type 5 inhibitors in heart failure with preserved ejection fraction and combined post- and pre-capillary pulmonary hypertension. Heart failure with preserved ejection fraction (HFpEF) is frequently associated with pulmonary hypertension (PH), which substantially impacts survival. Based on pulmonary vascular resistance (PVR) and the diastolic pressure gradient (DPG), current guidelines distinguish between isolated post-capillary PH (IpcPH) and combined

2019 International journal of cardiology

22. Sildenafil, a Phosphodiesterase Type 5 Inhibitor, augments sphincter bursting and bladder afferent activity to enhance storage function and voiding efficiency in mice. Full Text available with Trip Pro

Sildenafil, a Phosphodiesterase Type 5 Inhibitor, augments sphincter bursting and bladder afferent activity to enhance storage function and voiding efficiency in mice. To investigate the influence of low-dose sildenafil, a phosphodiesterase type 5 inhibitor (PDE5-I), on the function of the mouse lower urinary tract (LUT).Adult male mice were decerebrated and arterially perfused with a carbogenated Ringer's solution to establish the decerebrate arterially perfused mouse (DAPM). To allow

2019 BJU international

23. The use of phosphodiesterase inhibitors for the treatment of alopecia. (Abstract)

The use of phosphodiesterase inhibitors for the treatment of alopecia. Hair loss encompasses a group of scarring and nonscarring diseases with limited treatment options. Understanding the pathogenesis of alopecias has led to the experimental use of phosphodiesterase inhibitors (PDEi).To perform a systematic review of literature surrounding the use of PDEi for alopecia.A search was conducted using PubMed in February 2019 on PDEi and alopecia. Inclusion criteria were clinical trials, prospective

2019 Journal of Dermatological Treatment

24. The phosphodiesterase 5 inhibitor sildenafil decreases the proinflammatory chemokine IL-8 in diabetic cardiomyopathy: in vivo and in vitro evidence. Full Text available with Trip Pro

The phosphodiesterase 5 inhibitor sildenafil decreases the proinflammatory chemokine IL-8 in diabetic cardiomyopathy: in vivo and in vitro evidence. Interleukin (IL)-8 is a proinflammatory C-X-C chemokine involved in inflammation underling cardiac diseases, primary or in comorbid condition, such diabetic cardiomyopathy (DCM). The phosphodiesterase type 5 inhibitor sildenafil can ameliorate cardiac conditions by counteracting inflammation. The study aim is to evaluate the effect of sildenafil

2018 Journal of endocrinological investigation Controlled trial quality: uncertain

25. PF-04447943, a Phosphodiesterase 9A Inhibitor, in Stable Sickle Cell Disease Patients: A Phase Ib Randomized, Placebo-Controlled Study. Full Text available with Trip Pro

PF-04447943, a Phosphodiesterase 9A Inhibitor, in Stable Sickle Cell Disease Patients: A Phase Ib Randomized, Placebo-Controlled Study. This phase Ib study randomized patients with stable sickle cell disease (SCD) aged 18-65 years to twice-daily PF-04447943 (a phosphodiesterase 9A inhibitor; 5 or 25 mg) or placebo, with/without hydroxyurea coadministration, for up to 29 days. Blood samples were collected at baseline and various posttreatment time points for assessments of PF-04447943 (...) of circulating soluble E-selectin at day 29 vs. baseline (adjusted P < 0.15). PF-04447943 demonstrated PK/PD effects suggestive of inhibiting pathways that may contribute to vaso-occlusion. This study also provides guidance regarding biomarkers for future SCD studies.© 2018 Pfizer Inc. Clinical and Translational Science published by Wiley Periodicals, Inc. on behalf of the American Society for Clinical Pharmacology and Therapeutics.

2018 Clinical and translational science Controlled trial quality: uncertain

26. Oral L-citrulline and Transresveratrol Supplementation Improves Erectile Function in Men With Phosphodiesterase 5 Inhibitors: A Randomized, Double-Blind, Placebo-Controlled Crossover Pilot Study. Full Text available with Trip Pro

Oral L-citrulline and Transresveratrol Supplementation Improves Erectile Function in Men With Phosphodiesterase 5 Inhibitors: A Randomized, Double-Blind, Placebo-Controlled Crossover Pilot Study. Phosphodiesterase type 5 inhibitors (PDE5i) are first-line therapy for most men with erectile dysfunction (ED). If ineffective, vacuum erection devices, intracavernous injections, and penile prosthesis implantation are suitable as second- or third-line therapies. However, very few patients select (...) is effective for ED treatment in men with added on-demand use of PDE5i. This combination supplement may be added if PDE5i is insufficient. Shirai M, Hiramatsu I, Aoki Y, et al. Oral L-citrulline and Transresveratrol Supplementation Improves Erectile Function in Men With Phosphodiesterase 5 Inhibitors: A Randomized, Double-Blind, Placebo-Controlled Crossover Pilot Study. Sex Med 2018;6:291-296.Copyright © 2018. Published by Elsevier Inc.

2018 Sexual Medicine Controlled trial quality: uncertain

27. An experimental medicine study of the phosphodiesterase-4 inhibitor, roflumilast, on working memory-related brain activity and episodic memory in schizophrenia patients. Full Text available with Trip Pro

An experimental medicine study of the phosphodiesterase-4 inhibitor, roflumilast, on working memory-related brain activity and episodic memory in schizophrenia patients. Schizophrenia is associated with impairments in cognitive functioning yet there are no approved drugs to treat these deficits.Based on animal models, we investigated the potential for roflumilast, a selective inhibitor of phosphodiesterase type 4 (PDE4), to improve cognition, which may act by increasing intracellular cyclic (...) working memory compared to placebo, although this was not statistically significant (ES = 0.31 for the higher dose). Working memory was not improved (ES = 0.03).Results support the mechanistic validation of potential novel strategies for improving cognitive dysfunction in schizophrenia and suggest that PDE4 inhibition may be beneficial for cognitive dysfunction in schizophrenia.NCT02079844 .

2018 Psychopharmacology Controlled trial quality: uncertain

28. Phosphodiesterase type 5 inhibitor attenuates chronic ischemia-induced prostatic hyperplasia in a rat model. (Abstract)

Phosphodiesterase type 5 inhibitor attenuates chronic ischemia-induced prostatic hyperplasia in a rat model. Many elderly men suffer from benign prostatic hyperplasia (BPH). Recently, chronic ischemia in the prostate has been suggested to be related to BPH. Thus, the impact of chronic ischemia on the development of prostatic hyperplasia and the efficacy of phosphodiesterase type 5 (PDE5) inhibitor for hyperplasia were evaluated in a rat model with chronic ischemia induced by local (...) atherosclerosis.Eighteen male Sprague-Dawley rats were divided into three groups: sham operation, regular diet, placebo (SRP); arterial endothelial injury, high cholesterol diet, placebo (AHP); or arterial endothelial injury, high cholesterol diet, and tadalafil as a PDE5 inhibitor (AHT). The endothelial injury in the common iliac arteries was performed using a 2-Fr Fogarty arterial embolectomy catheter through an incision in the femoral artery into the common iliac artery. Diet and oral drugs were administrated for 8

2018 Prostate

29. The Phosphodiesterase Inhibitor Pentoxifylline as a Novel Adjunct to Antidepressants in Major Depressive Disorder Patients: A Proof-of-Concept, Randomized, Double-Blind, Placebo-Controlled Trial. (Abstract)

The Phosphodiesterase Inhibitor Pentoxifylline as a Novel Adjunct to Antidepressants in Major Depressive Disorder Patients: A Proof-of-Concept, Randomized, Double-Blind, Placebo-Controlled Trial. There is evidence for an association between major depressive disorder (MDD) and both inflammatory and phosphodiesterase (PDE) pathways. This study aimed to evaluate the adjunct role of the PDE inhibitor pentoxifylline (PTX), a compound with anti-inflammatory properties, in the treatment of adult

2018 Psychotherapy and Psychosomatics Controlled trial quality: uncertain

30. Pharmacokinetic disposition of topical phosphodiesterase-4 inhibitor E6005 in patients with atopic dermatitis. (Abstract)

Pharmacokinetic disposition of topical phosphodiesterase-4 inhibitor E6005 in patients with atopic dermatitis. A novel topical phosphodiesterase-4 inhibitor E6005 shows potential as effective treatment option for atopic dermatitis (AD); however, systemic exposure may cause potentially undesirable adverse reactions. In this study, we evaluated the relationship between the systemic exposure of E6005 and clinical parameters including skin condition and the incidence of AEs in patients with AD.The

2018 Journal of Dermatological Treatment Controlled trial quality: uncertain

31. Memory enhancing effects of BPN14770, an allosteric inhibitor of phosphodiesterase-4D, in wild-type and humanized mice. Full Text available with Trip Pro

Memory enhancing effects of BPN14770, an allosteric inhibitor of phosphodiesterase-4D, in wild-type and humanized mice. Inhibitors of phosphodiesterase-4 (PDE4) have beneficial effects on memory in preclinical and clinical studies. Development of these drugs has stalled due to dose-limiting side effects of nausea and emesis. While use of subtype-selective inhibitors (i.e., for PDE4A, B, or D) could overcome this issue, conservation of the catalytic region, to which classical inhibitors bind (...) , limits this approach. The present study examined the effects of BPN14770, an allosteric inhibitor of PDE4D, which binds to a primate-specific, N-terminal region. In mice engineered to express PDE4D with this primate-specific sequence, BPN14770 was 100-fold more potent for improving memory than in wild-type mice; meanwhile, it exhibited low potency in a mouse surrogate model for emesis. BPN14770 also antagonized the amnesic effects of scopolamine, increased cAMP signaling in brain, and increased BDNF

2018 Neuropsychopharmacology

32. Phosphodiesterase 2 inhibition preferentially promotes NO/guanylyl cyclase/cGMP signaling to reverse the development of heart failure Full Text available with Trip Pro

Phosphodiesterase 2 inhibition preferentially promotes NO/guanylyl cyclase/cGMP signaling to reverse the development of heart failure Heart failure (HF) is a shared manifestation of several cardiovascular pathologies, including hypertension and myocardial infarction, and a limited repertoire of treatment modalities entails that the associated morbidity and mortality remain high. Impaired nitric oxide (NO)/guanylyl cyclase (GC)/cyclic guanosine-3',5'-monophosphate (cGMP) signaling, underpinned (...) show that this beneficial pharmacodynamic profile is maintained in GC-A-/- mice but is absent in animals null for GC-1α or treated with a NO synthase inhibitor, revealing that PDE2 inhibition preferentially enhances NO/GC/cGMP signaling in the setting of HF to exert wide-ranging protection to preserve cardiac structure and function. These data substantiate the targeting of PDE2 in HF as a tangible approach to maximize myocardial cGMP signaling and enhancing therapy.Copyright © 2018 the Author(s

2018 Proceedings of the National Academy of Sciences of the United States of America

33. Targeting a Subpocket in Trypanosoma brucei Phosphodiesterase B1 (TbrPDEB1) Enables the Structure-Based Discovery of Selective Inhibitors with Trypanocidal Activity Full Text available with Trip Pro

Targeting a Subpocket in Trypanosoma brucei Phosphodiesterase B1 (TbrPDEB1) Enables the Structure-Based Discovery of Selective Inhibitors with Trypanocidal Activity Several trypanosomatid cyclic nucleotide phosphodiesterases (PDEs) possess a unique, parasite-specific cavity near the ligand-binding region that is referred to as the P-pocket. One of these enzymes, Trypanosoma brucei PDE B1 (TbrPDEB1), is considered a drug target for the treatment of African sleeping sickness. Here, we elucidate (...) the molecular determinants of inhibitor binding and reveal that the P-pocket is amenable to directed design. By iterative cycles of design, synthesis, and pharmacological evaluation and by elucidating the structures of inhibitor-bound TbrPDEB1, hPDE4B, and hPDE4D complexes, we have developed 4a,5,8,8a-tetrahydrophthalazinones as the first selective TbrPDEB1 inhibitor series. Two of these, 8 (NPD-008) and 9 (NPD-039), were potent ( Ki = 100 nM) TbrPDEB1 inhibitors with antitrypanosomal effects (IC50 = 5.5

2018 Journal of medicinal chemistry

34. Comparison of Effect of Leukotriene Biosynthesis Blockers and Inhibitors of Phosphodiesterase Enzyme in Patients with Bronchial Hyperreactivity Full Text available with Trip Pro

Comparison of Effect of Leukotriene Biosynthesis Blockers and Inhibitors of Phosphodiesterase Enzyme in Patients with Bronchial Hyperreactivity Blocking effect of leukotriene biosynthesis-zileuton and blocking the effect of phosphodiesterase enzyme-diprophylline in the treatment of patients with bronchial asthma and bronchial increased reactivity, and tiotropium bromide as an antagonist of the muscarinic receptor studied in this work.Parameters of the lung function are determined with Body (...) the significant decrease of the resistance (Raw), respectively of the specific resistance (SRaw), (p < 0.05).Effect of zileuton in blocking of leukotriene biosynthesis is not immediate after oral administration, but the effect seen on the third day of cys-LTs' inhibition, and leukotriene B4 (LTB4) and A4 (LTA4) in patients with bronchial reactivity and bronchial asthma, which is expressed with a high significance, (p < 0.01). Blockage of phosphodiesterase enzyme-diprophylline decreases the bronchial

2018 Open access Macedonian journal of medical sciences

35. Phosphodiesterase 4 inhibitor activates AMPK-SIRT6 pathway to prevent aging-related adipose deposition induced by metabolic disorder Full Text available with Trip Pro

Phosphodiesterase 4 inhibitor activates AMPK-SIRT6 pathway to prevent aging-related adipose deposition induced by metabolic disorder Rolipram is a selective phosphodiesterase 4 (PDE4) inhibitor that exerts a variety of effects, including anti-inflammatory, immunosuppressive, and anti-tumor effects. The aim of this study was to investigate the effect of rolipram on metabolic disorder and its underlying mechanisms. Metabolic disorder was induced in 8-week-old wild type BABL/c mice (...) in the liver and kidney while reducing NF-κB acetylation. In vitro, these effects were blocked by suppression of SIRT6 expression using specific siRNA. Increased cAMP levels reduced excessive adipose deposition, and improved adipose distribution in presenile mice. These findings provide a promising strategy for the treatment of aging-related metabolic dysfunctions and suggest that selective PDE4 inhibitors may be useful agents for the treatment of aging-related metabolic diseases.

2018 Aging (Albany NY)

36. Inhibition of Phosphodiesterase-4 Reverses Aβ-Induced Memory Impairment by Regulation of HPA Axis Related cAMP Signaling Full Text available with Trip Pro

Inhibition of Phosphodiesterase-4 Reverses Aβ-Induced Memory Impairment by Regulation of HPA Axis Related cAMP Signaling Beta amyloid peptides (Aβ) are found to be associated with dysfunction of hypothalamic-pituitary-adrenal axis (HPA axis) that leads to memory and cognitive deficits in patients with Alzheimer's disease (AD). Phosphodiesterase 4 (PDE4) inhibitors increase the intracellular cAMP activities, which may ameliorate cognitive deficits associated with AD. However, it remains unclear (...) whether PDE4-mediated reversal of cognitive impairment in mouse model of AD is related to HPA axis and downstream cAMP-dependent pathway. The present study investigated the effects of PDE4 inhibitor rolipram on Aβ1-42-induced cognitive dysfunction and its underlying mechanisms. The step-down passive avoidance (PA) and Morris water-maze (MWM) tests were conducted 1 week (1 W), 2 months (2 M), and 6 months (6 M) after intracerebroventricular microjection (i.c.v.) of Aβ1-42. The results suggested

2018 Frontiers in aging neuroscience

37. Phosphodiesterase-4 Inhibitors for the Treatment of Inflammatory Diseases Full Text available with Trip Pro

Phosphodiesterase-4 Inhibitors for the Treatment of Inflammatory Diseases Phosphodiesterase-4 (PDE4), mainly present in immune cells, epithelial cells, and brain cells, manifests as an intracellular non-receptor enzyme that modulates inflammation and epithelial integrity. Inhibition of PDE4 is predicted to have diverse effects via the elevation of the level of cyclic adenosine monophosphate (cAMP) and the subsequent regulation of a wide array of genes and proteins. It has been identified (...) that PDE4 is a promising therapeutic target for the treatment of diverse pulmonary, dermatological, and severe neurological diseases. Over the past decades, numerous PDE4 inhibitors have been designed and synthesized, among which roflumilast, apremilast, and crisaborole were approved for the treatment of inflammatory airway diseases, psoriatic arthritis, and atopic dermatitis, respectively. It is regrettable that the dramatic efficacies of a drug are often accompanied by adverse effects, such as nausea

2018 Frontiers in pharmacology

38. Safety, tolerability, and pharmacokinetics of single and repeat ascending doses of CHF6001, a novel inhaled phosphodiesterase-4 inhibitor: two randomized trials in healthy volunteers Full Text available with Trip Pro

Safety, tolerability, and pharmacokinetics of single and repeat ascending doses of CHF6001, a novel inhaled phosphodiesterase-4 inhibitor: two randomized trials in healthy volunteers The purpose of this study was to evaluate safety, tolerability, and pharmacokinetics (PK) of CHF6001, an inhaled phosphodiesterase-4 inhibitor.Two healthy volunteer, randomized, double-blind, placebo-controlled studies were conducted. In each, Part 1 evaluated single ascending doses, with PK sampling up to 48 hours

2018 International journal of chronic obstructive pulmonary disease Controlled trial quality: uncertain

39. A Novel Class of Tyrosyl-DNA Phosphodiesterase 1 Inhibitors That Contains the Octahydro-2H-chromen-4-ol Scaffold Full Text available with Trip Pro

A Novel Class of Tyrosyl-DNA Phosphodiesterase 1 Inhibitors That Contains the Octahydro-2H-chromen-4-ol Scaffold Tyrosyl-DNA phosphodiesterase 1 (Tdp1) is a DNA repair enzyme that mends topoisomerase 1-mediated DNA damage. Tdp1 is a current inhibition target for the development of improved anticancer treatments, as its inhibition may enhance the therapeutic effect of topoisomerase 1 poisons. Here, we report a study on the development of a novel class of Tdp1 inhibitors that is based (...) on the octahydro-2H-chromene scaffold. Inhibition and binding assays revealed that these compounds are potent inhibitors of Tdp1, with IC50 and KD values in the low micromolar concentration range. Molecular modelling predicted plausible conformations of the active ligands, blocking access to the enzymatic machinery of Tdp1. Our results thus help establish a structural-activity relationship for octahydro-2H-chromene-based Tdp1 inhibitors, which will be useful for future Tdp1 inhibitor development work.

2018 Molecules : A Journal of Synthetic Chemistry and Natural Product Chemistry

40. Treatment Selection in Pulmonary Arterial Hypertension: Phosphodiesterase Type 5 Inhibitors versus Soluble Guanylate Cyclase Stimulator Full Text available with Trip Pro

Treatment Selection in Pulmonary Arterial Hypertension: Phosphodiesterase Type 5 Inhibitors versus Soluble Guanylate Cyclase Stimulator Pulmonary arterial hypertension is a chronic and life-threatening disease that if left untreated is fatal. Current therapies include stimulating the nitric oxide-soluble guanylate cyclase (sGC)-cyclic guanosine monophosphate axis, improving the prostacyclin pathway and inhibiting the endothelin pathway. Phosphodiesterase type 5 inhibitors, such as sildenafil (...) , and the sGC stimulator riociguat are currently used in the treatment of pulmonary arterial hypertension. This article discusses the similarities and differences between phosphodiesterase type 5 inhibitors and sGC stimulator based on pharmacological action and clinical trials, and considers which is better for the treatment of pulmonary arterial hypertension.

2018 European Cardiology Review

To help you find the content you need quickly, you can filter your results via the categories on the right-hand side >>>>