96,762 results match your criteria phosphodiesterase inhibitors


Sildenafil in endotoxin-induced pulmonary hypertension: an experimental study.

Braz J Anesthesiol 2021 Jun 9. Epub 2021 Jun 9.

Universidade de São Paulo, Faculdade de Medicina Veterinária e Zootecnia, Departamento de Cirurgia, São Paulo, SP, Brazil.

Background: Sepsis and septic shock still represent great challenges in critical care medicine. Sildenafil has been largely used in the treatment of pulmonary arterial hypertension, but its effects in sepsis are unknown. The aim of this study was to investigate the hypothesis that sildenafil can attenuate endotoxin-induced pulmonary hypertension in a porcine model of endotoxemia. Read More

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Phosphodiesterase 10A Is a Key Mediator of Lung Inflammation.

J Immunol 2021 Jun 11. Epub 2021 Jun 11.

Department of Medicine, Aab Cardiovascular Research Institute, University of Rochester School of Medicine and Dentistry, Rochester, NY; and

Cyclic nucleotides cAMP and cGMP are important regulators of immune cell functions. Phosphodiesterases (PDEs) hydrolyze cAMP and/or cGMP and, thus, play crucial roles in cyclic nucleotide homeostasis. Abnormal alterations of PDE expression have been implicated in several diseases. Read More

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Phosphodiesterase-5 inhibitors in Pregnancy: Systematic review and meta-analysis of maternal and perinatal safety and clinical outcomes.

Am J Obstet Gynecol 2021 Jun 8. Epub 2021 Jun 8.

Mater Research Institute - University of Queensland, Level 3 Aubigny Place, Raymond Terrace, South Brisbane, Queensland 4101, Australia; Faculty of Medicine, University of Medicine, Whitty Building, Annerley Road, South Brisbane, Queensland 4101, Australia; NHMRC Stillbirth Centre For Research Excellence, Mater Research Institute, South Brisbane, Queensland 4101, Australia. Electronic address:

Objective: Phosphodiesterase-5 inhibitors have recently been used for the treatment of severe early onset pre-eclampsia and fetal growth restriction. There are however concerns that they may increase the risk of neonatal morbidity and mortality. The aim of this systematic review was to assess the safety profile and clinical outcomes of phosphodiesterase-5 inhibitors use in pregnancy. Read More

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Structure-based redesigning of pentoxifylline analogs against selective phosphodiesterases to modulate sperm functional competence for assisted reproductive technologies.

Sci Rep 2021 Jun 10;11(1):12293. Epub 2021 Jun 10.

Macromolecular Structural Biology Lab, Department of Biotechnology, Indian Institute of Technology Hyderabad, Kandi, Sangareddy, Telangana, 502285, India.

Phosphodiesterase (PDE) inhibitors, such as pentoxifylline (PTX), are used as pharmacological agents to enhance sperm motility in assisted reproductive technology (ART), mainly to aid the selection of viable sperm in asthenozoospermic ejaculates and testicular spermatozoa, prior to intracytoplasmic sperm injection (ICSI). However, PTX is reported to induce premature acrosome reaction (AR) and, exert toxic effects on oocyte function and early embryo development. Additionally, in vitro binding studies as well as computational binding free energy (ΔG) suggest that PTX exhibits weak binding to sperm PDEs, indicating room for improvement. Read More

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Identification and treatment of T2-low asthma in the era of biologics.

ERJ Open Res 2021 Apr 7;7(2). Epub 2021 Jun 7.

Respiratory Medicine Dept, University of Ioannina School of Medicine, Ioannina, Greece.

Currently, and based on the development of relevant biologic therapies, T2-high is the most well-defined endotype of asthma. Although much progress has been made in elucidating T2-high inflammation pathways, no specific clinically applicable biomarkers for T2-low asthma have been identified. The therapeutic approach of T2-low asthma is a problem urgently needing resolution, firstly because these patients have poor response to steroids, and secondly because they are not candidates for the newer targeted biologic agents. Read More

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Quality of cosmetics with active caffeine in cream and gel galenic bases prepared by compounding pharmacies.

Braz J Biol 2021 2;82:e241043. Epub 2021 Jun 2.

Universidade Tecnológica Federal do Paraná - UTFPR, Programa de Pós-graduação em Inovações Tecnológicas - PPGIT, Campo Mourão, PR, Brasil.

As there is a great scarcity of studies on the importance of good compounding practices in the preparation of cosmetics, this study aimed to evaluate the quality control of cosmetics with active ingredient caffeine for the treatment of cellulite prepared by magistrals pharmacies. Microbiological analyzes, pH determination, color measurement, quantification of the percentage of the active ingredient caffeine and viscosity in creams and gels with 5% of the active ingredient caffeine were performed. In the microbiological analysis, the presence of molds and yeasts was verified above the permitted level according to the Brazilian pharmacopoeia. Read More

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Challenges of nanotechnology in cosmetic permeation with caffeine.

Braz J Biol 2021 2;82:e241025. Epub 2021 Jun 2.

Universidade Tecnológica Federal do Paraná, Programa de Pós-Graduação em Inovações Tecnológicas - PPGIT, Campo Mourão, PR, Brasil.

The evolution of beauty market and personal care is constant in Brazil as well in the rest of the world. Technological advances have brought up nanotechnology to the cosmetological field, employing active principles at atoms enveloped by vesicles, in order to take the active principle precisely to the target tissue to optimize the results achieved because of the considerable ease to cross skin barriers. Manufacturing of nanotechnology cosmetics is confronted with low absorption capacity. Read More

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Evolution of randomized, controlled studies of medical therapy in chronic thromboembolic pulmonary hypertension.

Pulm Circ 2021 Apr-Jun;11(2):20458940211007373. Epub 2021 May 24.

Department of Medicine, University of California San Diego, La Jolla, CA, USA.

Although pulmonary endarterectomy (PEA) is the treatment of choice for chronic thromboembolic pulmonary hypertension (CTEPH), many patients have inoperable disease, and some have persistent or recurrent pulmonary hypertension (PH) after surgery. Alternative options (balloon pulmonary angioplasty (BPA) and PH-targeted medical therapy) are, therefore, required. Studies of medical therapies for CTEPH have evolved since Aerosolized Iloprost Randomized (AIR), the first randomized, controlled study of a PH-targeted therapy (inhaled iloprost) to include patients with CTEPH. Read More

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STIMULATION OF THE CYCLIC AMP/GMP SIGNALLING ENHANCES THE RELAXATION OF ISOLATED HUMAN DETRUSOR SMOOTH MUSCLE ACHIEVED BY PHOSPHODIESTERASE INHIBITORS.

Georgian Med News 2021 Apr(313):7-12

2Hannover Medical School, Division of Surgery, Department of Urology & Urological Oncology; 5DIAKOVERE GmbH, Friederikenstft Lutheran Hospital, Department of Urology, Hannover, Germany.

Phosphodiesterase (PDE) enzymes are considered being key proteins in controlling the function of smooth musculature in the human urinary tract. The use of PDE inhibitors (PDE-Is) to treat erectile dysfunction and lower urinary tract symptomatology (LUTS) secondary to benign prostatic hyperplasia (BPH) is well established. It has been shown that PDE-Is can reverse the tension induced by means of muscarinergic agents of detrusor smooth muscle and enhance the production of cyclic nucleotides. Read More

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Male Sexual Dysfunctions in the Infertile Couple-Recommendations From the European Society of Sexual Medicine (ESSM).

Sex Med 2021 Jun 2;9(3):100377. Epub 2021 Jun 2.

Endocrinology Unit, Medical Department, Azienda USL, Maggiore-Bellaria Hospital, Bologna, Italy.

Introduction: Sexual dysfunctions (SDs) have been frequently reported among male partners of infertile couples due to psychogenic, relational and/or organic issues related with the inability to conceive. Likewise, male infertility (MI) could be a consequence of sexual dysfunctions.

Aim: To review the evidence on the prevalence and treatment of male SDs in men of infertile couples and provide clinical recommendations on behalf of the European Society of Sexual Medicine (ESSM). Read More

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Selective inhibition of phosphodiesterase 7 enzymes reduces motivation for nicotine use through modulation of mesolimbic dopaminergic transmission.

J Neurosci 2021 Jun 1. Epub 2021 Jun 1.

Omeros Corporation, 201 Elliot Avenue West, Seattle, WA 98119, USA

: About 5 million people die from diseases related to nicotine addiction and tobacco use each year. Nicotine-induced increase of corticomesolimbic dopaminergic (DAergic) transmission and hypodopaminergic conditions occurring during abstinence are important for maintaining drug-use habits. : We examined the notion of re-equilibrating DAergic transmission by inhibiting phosphodiesterase 7 (PDE7), an intracellular enzyme highly expressed in the corticomesolimbic circuitry and responsible for the degradation of cyclic adenosine monophosphate (cAMP), the main second messenger modulated by DA receptor activation. Read More

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Tuning bio-aerogel properties for controlling theophylline delivery. Part 1: Pectin aerogels.

Mater Sci Eng C Mater Biol Appl 2021 Jul 30;126:112148. Epub 2021 Apr 30.

MINES ParisTech, PSL Research University, Center for Materials Forming (CEMEF), UMR CNRS 7635, CS 10207, 06904 Sophia Antipolis, France. Electronic address:

A comprehensive study of release kinetics of a hydrophilic drug from bio-aerogels based on pectin was performed. Pectin aerogels were made by polymer dissolution, gelation (in some cases this step was omitted), solvent exchange and drying with supercritical CO. Theophylline was loaded and its release was studied in the simulated gastric fluid during 1 h followed by the release in the simulated intestinal fluid. Read More

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What's new in atopic eczema? An analysis of systematic reviews published in 2019. Part 2: Treatment.

Clin Exp Dermatol 2021 Jun 3. Epub 2021 Jun 3.

Biosciences Institute, Newcastle University, Newcastle upon Tyne, NE1 7RU, UK.

This review forms part of a series of annual evidence updates on atopic eczema (AE), and provides a summary of key findings from systematic reviews (SRs) published or indexed in 2019 related to AE treatment. Several SRs assessed the efficacy of topical corticosteroids (TCSs), topical calcineurin inhibitors, topical phosphodiesterase 4 inhibitors and topical JAK/STAT pathway inhibitors. However, there is a lack of good quality trials comparing topical treatment agents to TCSs, which remain the standard of care for patients with AE. Read More

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The safety of phosphodiesterase-5 inhibitors in valvular heart disease.

J Cardiovasc Pharmacol 2021 May 27. Epub 2021 May 27.

Division of Cardiology, Medical College of Georgia at Augusta University.

Abstract: Erectile dysfunction is a common entity in clinical practice. Primary erectile dysfunction not related to vasculopathy or psychiatric disorder, can be readily treated with phosphodiesterase inhibitors. These drugs have many physiologic effects which can alter a patient's hemodynamic profile considerably, especially in the presence of concomitant structural heart disease, specifically valvular heart disease. Read More

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Novel therapies and the potential for a personalized approach to atopic dermatitis.

Curr Opin Allergy Clin Immunol 2021 Jun 1. Epub 2021 Jun 1.

Department of Dermatology, Allergology and Dermatosurgery, HELIOS University Hospital Wuppertal, University of Witten/Herdecke, Wuppertal Department of Dermatology and Allergology, University Hospital of Bonn, Bonn, Germany.

Purpose Of The Review: To provide a cutting-edge overview of recent developments in topical and systemic therapeutic approaches for the treatment of atopic dermatitis (AD).

Recent Findings: Growing knowledge about key pathways in AD and stratification of patient's subgroups have set the basis for a new era of targeted topical and systemic therapy in AD.Different aspects have to be considered in the decision process for topical versus systemic therapy. Read More

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A malachite green light-up aptasensor for the detection of theophylline.

Talanta 2021 Sep 20;232:122417. Epub 2021 Apr 20.

Univ Bordeaux, CNRS, Inserm, ARNA, UMR5320, U1212, F-33000, Bordeaux, France; Novaptech, F-33600, Pessac, France. Electronic address:

Biosensors are of interest for the quantitative detection of small molecules (metabolites, drugs and contaminants for instance). To this end, fluorescence is a widely used technique that is easily associated to aptamers. Light-up aptamers constitute a particular class of oligonucleotides that, specifically induce fluorescence emission when binding to cognate fluorogenic ligands such as malachite green (MG). Read More

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September 2021

Vericiguat for the treatment of heart failure: mechanism of action and pharmacological properties compared with other emerging therapeutic options.

Expert Opin Pharmacother 2021 Jun 9:1-9. Epub 2021 Jun 9.

Centre Hospitalier Universitaire de Nancy Brabois, Vandoeuvre Lès Nancy, France.

Introduction: The significant morbidity and mortality in patients with heart failure (HF), notably in the most advanced forms of the disease, justify the need for novel therapeutic options. In the last year, the soluble guanylate cyclase (sGC) stimulator, vericiguat, has drawn the attention of the medical community following the report of reduced clinical outcomes in patients with worsening chronic HF (WCHF).

Areas Covered: The authors review the available data on the mechanism of action of vericiguat (cyclic guanosine monophosphate (cGMP) pathway), its clinical development program, its role in HF management, and its future positioning in the therapeutic recommendations. Read More

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Novel Tdp1 Inhibitors Based on Adamantane Connected with Monoterpene Moieties via Heterocyclic Fragments.

Molecules 2021 May 24;26(11). Epub 2021 May 24.

Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of Russian Academy of Sciences, 8, Lavrentiev Ave., 630090 Novosibirsk, Russia.

Tyrosyl-DNA phosphodiesterase 1 (Tdp1) is a promising target for anticancer therapy due to its ability to counter the effects topoisomerase 1 (Top1) poison, such as topotecan, thus, decreasing their efficacy. Compounds containing adamantane and monoterpenoid residues connected via 1,2,4-triazole or 1,3,4-thiadiazole linkers were synthesized and tested against Tdp1. All the derivatives exhibited inhibition at low micromolar or nanomolar concentrations with the most potent inhibitors having IC values in the 0. Read More

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Design, Synthesis, and Biological Evaluation of Novel 6-Benzo[]chromen-6-one Derivatives as Potential Phosphodiesterase II Inhibitors.

Int J Mol Sci 2021 May 26;22(11). Epub 2021 May 26.

School of Pharmaceutical Engineering & Life Science, Changzhou University, Changzhou 213164, China.

Urolithins (hydroxylated 6-benzo[]chromen-6-ones) are the main bioavailable metabolites of ellagic acid (EA), which was shown to be a cognitive enhancer in the treatment of neurodegenerative diseases. As part of this research, a series of alkoxylated 6-benzo[]chromen-6-one derivatives were designed and synthesized. Furthermore, their biological activities were evaluated as potential PDE2 inhibitors, and the alkoxylated 6-benzo[]chromen-6-one derivative was found to have the optimal inhibitory potential (IC: 3. Read More

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Design, Synthesis, and Evaluation of Dihydropyranopyrazole Derivatives as Novel PDE2 Inhibitors for the Treatment of Alzheimer's Disease.

Molecules 2021 May 19;26(10). Epub 2021 May 19.

School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, China.

Phosphodiesterase 2 (PDE2) has been regarded as a novel target for the treatment of Alzheimer's disease (AD). In this study, we obtained ()- as a hit compound with moderate PDE2 inhibitory activity (IC = 261.3 nM) using a high-throughput virtual screening method based on molecular dynamics. Read More

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Modulation of Cyclic AMP Levels in Fallopian Tube Cells by Natural and Environmental Estrogens.

Cells 2021 May 19;10(5). Epub 2021 May 19.

Department of Reproductive Endocrinology, University Hospital Zurich, Areal Wagi Schlieren, Wagistrasse 14, CH 8952 Schlieren, Switzerland.

Autocrine/paracrine factors generated in response to 17β-estradiol (E2) within the fallopian tube (FT) facilitate fertilization and early embryo development for implantation. Since cyclic AMP (cAMP) plays a key role in reproduction, regulation of its synthesis by E2 may be of biological/pathophysiological relevance. Herein, we investigated whether cAMP production in FT cells (FTCs) is regulated by E2 and environmental estrogens (EE's; xenoestrogens and phytoestrogens). Read More

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Possible Beneficial Actions of Caffeine in SARS-CoV-2.

Int J Mol Sci 2021 May 22;22(11). Epub 2021 May 22.

Departamento de Farmacología, Facultad de Medicina, Universidad Nacional Autónoma de México, CDMX CP 04510, Mexico.

The COVID-19 pandemic has established an unparalleled necessity to rapidly find effective treatments for the illness; unfortunately, no specific treatment has been found yet. As this is a new emerging chaotic situation, already existing drugs have been suggested to ameliorate the infection of SARS-CoV-2. The consumption of caffeine has been suggested primarily because it improves exercise performance, reduces fatigue, and increases wakefulness and awareness. Read More

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Selective Inhibition of PDE4B Reduces Binge Drinking in Two C57BL/6 Substrains.

Int J Mol Sci 2021 May 21;22(11). Epub 2021 May 21.

Department of Psychological and Brain Sciences, University of California Santa Barbara, Santa Barbara, CA 93106-9660, USA.

Cyclic AMP (cAMP)-dependent signaling is highly implicated in the pathophysiology of alcohol use disorder (AUD), with evidence supporting the efficacy of inhibiting the cAMP hydrolyzing enzyme phosphodiesterase 4 (PDE4) as a therapeutic strategy for drinking reduction. Off-target emetic effects associated with non-selective PDE4 inhibitors has prompted the development of selective PDE4 isozyme inhibitors for treating neuropsychiatric conditions. Herein, we examined the effect of a selective PDE4B inhibitor A33 (0-1. Read More

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Development of Phosphodiesterase-Protein-Kinase Complexes as Novel Targets for Discovery of Inhibitors with Enhanced Specificity.

Int J Mol Sci 2021 May 15;22(10). Epub 2021 May 15.

Department of Biological Sciences, 14 Science Drive 4, National University of Singapore, Singapore 117543, Singapore.

Phosphodiesterases (PDEs) hydrolyze cyclic nucleotides to modulate multiple signaling events in cells. PDEs are recognized to actively associate with cyclic nucleotide receptors (protein kinases, PKs) in larger macromolecular assemblies referred to as signalosomes. Complexation of PDEs with PKs generates an expanded active site that enhances PDE activity. Read More

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Design, Synthesis, and Molecular Docking Study of New Tyrosyl-DNA Phosphodiesterase 1 (TDP1) Inhibitors Combining Resin Acids and Adamantane Moieties.

Pharmaceuticals (Basel) 2021 May 1;14(5). Epub 2021 May 1.

N. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences, Lavrentiev Ave. 9, 630090 Novosibirsk, Russia.

In this paper, a series of novel abietyl and dehydroabietyl ureas, thioureas, amides, and thioamides bearing adamantane moieties were designed, synthesized, and evaluated for their inhibitory activities against tyrosil-DNA-phosphodiesterase 1 (TDP1). The synthesized compounds were able to inhibit TDP1 at micromolar concentrations (0.19-2. Read More

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Efficacy of a Novel Penile Traction Device in Improving Penile Length and Erectile Function Post Prostatectomy: Results from a Single-Center Randomized, Controlled Trial.

J Urol 2021 Jun 1:101097JU0000000000001792. Epub 2021 Jun 1.

Mayo Clinic, Rochester, Minnesota.

Purpose: RestoreX is a novel penile traction therapy device, with randomized, controlled data demonstrating improvements in penile length and erectile function after 30 to 90 minutes of daily use in men with Peyronie's disease. We sought to determine if similar improvements could be achieved post prostatectomy.

Materials And Methods: Men post prostatectomy were randomly assigned to control or one of 2 penile traction therapy protocols for 6 months, followed by a 3-month open-label phase. Read More

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Guanylyl cyclase 2C (GUCY2C) in gastrointestinal cancers: recent innovations and therapeutic potential.

Expert Opin Ther Targets 2021 Jun 15:1-12. Epub 2021 Jun 15.

Department of Pharmacology and Experimental Therapeutics, Thomas Jefferson University, Philadelphia, PA, USA.

Introduction: Gastrointestinal (GI) cancers account for the second leading cause of cancer-related deaths in the United States. Guanylyl cyclase C (GUCY2C) is an intestinal signaling system that regulates intestinal fluid and electrolyte secretion as well as intestinal homeostasis. In recent years, it has emerged as a promising target for chemoprevention and therapy for GI malignancies. Read More

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Phosphodiesterase Type 5 Inhibitors and Visual Side Effects: A Narrative Review.

J Ophthalmic Vis Res 2021 Apr-Jun;16(2):248-259. Epub 2021 Apr 29.

Federal University of Ceara, Fortaleza, Ceara, Brazil.

Phosphodiesterase type 5 inhibitors such as sildenafil citrate and tadalafil are well known for the treatment of erectile dysfunction. However, their use in the presence of pulmonary hypertension can cause ophthalmologic side effects, including non-arteritic optic ischemic neuropathy, chorioretinopathy, glaucoma, and optic atrophy. The present review aimed to identify these visual side effects and provide recommendations. Read More

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Erectile dysfunction and penile rehabilitation after pelvic fracture: a systematic review and meta-analysis.

BMJ Open 2021 05 28;11(5):e045117. Epub 2021 May 28.

Department of Trauma, University Hospital Zurich, University of Zurich, Zurich, Switzerland

Objective: To investigate the rate of erectile dysfunction (ED) after pelvic ring fracture (PRF).

Design: Systematic review and meta-analysis.

Methods: A systematic literature search of the Cochrane, EMBASE, MEDLINE, Scopus and Web of Science Library databases was conducted in January 2020. Read More

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Pyridazinone derivatives as potential anti-inflammatory agents: synthesis and biological evaluation as PDE4 inhibitors.

RSC Med Chem 2021 Apr 1;12(4):584-592. Epub 2021 Mar 1.

Université de Reims Champagne-Ardenne, Institut de Chimie Moléculaire de Reims (ICMR), UMR CNRS 7312, UFR Sciences, Moulin de la housse and UFR Pharmacie 51 rue Cognacq-Jay F-51096 Reims France

Cyclic nucleotide phosphodiesterase type 4 (PDE4), which controls the intracellular level of cyclic adenosine monophosphate (cAMP), has aroused scientific attention as a suitable target for anti-inflammatory therapy of respiratory diseases. This work describes the development and characterization of pyridazinone derivatives bearing an indole moiety as potential PDE4 inhibitors and their evaluation as anti-inflammatory agents. Among these derivatives, 4-(5-methoxy-1-indol-3-yl)-6-methylpyridazin-3(2)-one possesses promising activity, and selectivity towards PDE4B isoenzymes and is able to regulate potent pro-inflammatory cytokine and chemokine production by human primary macrophages. Read More

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