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PDE 5 Inhibitors

Rania R Abdelaziz, Wagdi F Elkashef, Eman Said
Silicosis is a crippling respiratory disorder characterized by massive lung inflammation and fibrosis. The current study provides evidence on the protective potential of tadalafil; a specific phosphodiesterase-5 (PDE-5) inhibitor against experimentally-induced pulmonary silicosis in rats. Silicosis was induced by intranasal instillation of crystalline silica (50mg/rat). Halofuginone hydrobromide; a standard collagen-1 synthesis inhibitor was selected as a reference anti-fibrotic. Daily oral administration of tadalafil (1mg/kg) for 8weeks significantly ameliorated silica-induced pulmonary damage...
October 18, 2016: International Immunopharmacology
Szczepan Mogilski, Monika Kubacka, Dorota Łażewska, Małgorzata Więcek, Monika Głuch-Lutwin, Małgorzata Tyszka-Czochara, Karolina Bukowska-Strakova, Barbara Filipek, Katarzyna Kieć-Kononowicz
OBJECTIVE AND DESIGN: Histamine H4 receptor (H4R) offers a great potential for new therapeutic strategies for the treatment of inflammation-based diseases. The aim of this study is to present the pharmacological profile of two recently synthesized ligands of H4R with particular reference to their anti-inflammatory and analgesic activity. MATERIALS AND SUBJECTS: We used mice and rats in the in vivo tests. We also used murine RAW 264.7 cells and isolated guinea-pig ileum in in vitro test...
October 20, 2016: Inflammation Research: Official Journal of the European Histamine Research Society ... [et Al.]
Tomomichi Ishizaka, Yu Yoshimatsu, Yu Maeda, Wataru Takasaki, Katsuyoshi Chiba, Kazuhiko Mori
INTRODUCTION: Load-independent cardiac parameters obtained from the ventricular pressure-volume relationship are recognized as gold standard indexes for evaluating cardiac inotropy.In this study, for better analyses of cardiac risks, load-independent pressure-volume loop parameters were assessed in addition to load-dependent inotropic, hemodynamic and electrocardiographic changes in isoflurane-anesthetized monkeys. METHODS: The animals were given milrinone (a PDE 3 inhibitor), metoprolol (a β-blocker), or dl-sotalol (a β+IKr blocker) intravenously over 10min at two dose levels including clinically relevant doses (n=5/drug)...
October 15, 2016: Journal of Pharmacological and Toxicological Methods
Hui Liu, Hongjun Jin, Xuyi Yue, Junbin Han, Hao Yang, Hubert Flores, Yi Su, David Alagille, Joel S Perlmutter, Gilles Tamagnan, Zhude Tu
Phosphodiesterase 10A (PDE10A) inhibitors show therapeutic effects for diseases with striatal pathology. PET radiotracers have been developed to quantify in vivo PDE10A levels and target engagement for therapeutic interventions. The aim of this study was to compare two potent and selective PDE10A radiotracers, [(11)C]TZ1964B and [(18)F]MNI659 in the nonhuman primate (NHP) brain. Double scans in the same cynomolgus monkey on the same day were performed after injection of [(11)C]TZ1964B and [(18)F]MNI659. Specific uptake was determined in two ways: nondisplaceable binding potential (BPND) was calculated using cerebellum as the reference region and the PDE-10A enriched striatum as the target region of interest (ROI); the area under the time-activity curve (AUC) for the striatum to cerebellum ratio was also calculated...
October 2016: Pharmacology Research & Perspectives
Isabelle Karine da Costa Nunes, Everton Tenório de Souza, Suzana Vanessa S Cardozo, Vinicius de Frias Carvalho, Nelilma Correia Romeiro, Patrícia Machado Rodrigues E Silva, Marco Aurélio Martins, Eliezer J Barreiro, Lídia Moreira Lima
Prior investigations showed that increased levels of cyclic AMP down-regulate lung inflammatory changes, stimulating the interest in phosphodiesterase (PDE)4 as therapeutic target. Here, we described the synthesis, pharmacological profile and docking properties of a novel sulfonamide series (5 and 6a-k) designed as PDE4 inhibitors. Compounds were screened for their selectivity against the four isoforms of human PDE4 using an IMAP fluorescence polarized protocol. The effect on allergen- or LPS-induced lung inflammation and airway hyper-reactivity (AHR) was studied in A/J mice, while the xylazine/ketamine-induced anesthesia test was employed as a behavioral correlate of emesis in rodents...
2016: PloS One
Eva Degerman, Rene In 't Zandt, Annki Pålbrink, Lena Eliasson, Per Cayé-Thomasen, Måns Magnusson
CONCLUSION: The data indicate important roles for phosphodiesterase (PDE) 3, 4, 5, and related cAMP and cGMP pools in the regulation of inner ear fluid homeostasis. Thus, dysfunction of these enzymes might contribute to pathologies of the inner ear. OBJECTIVE: The mechanisms underlying endolymphatic hydrops, a hallmark of inner ear dysfunction, are not known in detail; however, altered balance in cAMP and cGMP signaling systems appears to be involved. Key components of these systems are PDEs, enzymes that modulate the amplitude, duration, termination, and specificity of cAMP and cGMP signaling...
August 15, 2016: Acta Oto-laryngologica
L Bacconi, F Gressier
INTRODUCTION: Sexual dysfunction is an important public health problem in men and is associated with reduced quality of life. It is more common in patients with schizophrenia. It is well-established that antipsychotic drugs cause sexual dysfunction with consequences on the quality of life of patients, adherence to treatment, and public health costs. Phosphodiesterase type 5 inhibitors (PDE5 inhibitors) are indicated for the management of erectile dysfunction. However, there is little information on such treatment in schizophrenic patients...
September 19, 2016: L'Encéphale
Chris G McMahon
Over the past 20-30 years, the premature ejaculation (PE) treatment paradigm, previously limited to behavioural psychotherapy, has expanded to include drug treatment. Pharmacotherapy for PE predominantly targets the multiple neurotransmitters and receptors involved in the control of ejaculation which include serotonin, dopamine, oxytocin, norepinephrine, gamma amino-butyric acid (GABA) and nitric oxide (NO). The objective of this article is to review emerging PE interventions contemporary data on the treatment of PE was reviewed and critiqued using the principles of evidence-based medicine...
August 2016: Translational Andrology and Urology
Simone Albisinni, Ibrahim Biaou, Quentin Marcelis, Fouad Aoun, Cosimo De Nunzio, Thierry Roumeguère
BACKGROUND: Lower Urinary Tract Symptoms (LUTS) in men are a common clinical problem in urology and have been historically strictly linked to benign prostatic hyperplasia (BPH), which may lead to bladder outlet obstruction (BOO). New molecules have been approved and have entered the urologists' armamentarium, targeting new signaling pathways and tackling specific aspects of LUTS. Objective of this review is to summarize the evidence regarding the new medical therapies currently available for male non-neurogenic LUTS, including superselective α1-antagonists, PDE-5 inhibitors, anticholinergic drugs and intraprostatic onabotulinum toxin injections...
September 15, 2016: BMC Urology
Petros V Vlastarakos, Thomas P Nikolopoulos
BACKGROUND: Phosphodiesterase-5 (PDE-5) inhibitors enhance penile erection and have gained popularity not only for erectile dysfunction, but also in recreational settings. Nevertheless, adverse effects have been associated with their use, with nasal bleeding among them. PDE-5 inhibitor action is materialized through the inhibition of the cyclic guanosine monophosphate (cGMP) enzyme. cGMP is present at several sites of the human body in addition to the corpus cavernosum, leading to the adverse effects associated with its nonselective inhibition...
September 10, 2016: Journal of Emergency Medicine
Gülru Kayık, Nurcan Ş Tüzün, Serdar Durdagi
Cyclic nucleotide phosphodiesterase enzymes (PDEs) have functions in regulating the levels of intracellular second messengers, 3', 5'-cyclic adenosine monophosphate (cAMP) and 3', 5'-cyclic guanosine monophosphate (cGMP), via hydrolysis and decomposing mechanisms in cells. They take essential roles in modulating various cellular activities such as memory and smooth muscle functions. PDE type 5 (PDE5) inhibitors enhance the vasodilatory effects of cGMP in the corpus cavernosum and they are used to treat erectile dysfunction...
October 6, 2016: Journal of Biomolecular Structure & Dynamics
S Frees, P Rubenwolf, C Ziesel, J Faber, P Gutjahr, A Grossmann, J W Thüroff, R Stein
INTRODUCTION: Rhabdomyosarcoma (RMS) accounts for 5% of all pediatric tumors; 15-20% of these tumors are located in the urogenital tract, mostly originating from the prostate or bladder. In the light of the steadily improving prognosis for patients with RMS through interdisciplinary-multimodal study protocols with 60-70% long-term survivors, non oncological aspects such as erectile function (EF) have become increasingly important. The aim of this study was to evaluate EF in patients having undergone treatment for RMS of the bladder and prostate...
August 1, 2016: Journal of Pediatric Urology
Asger Andersen, Jonas Agerlund Povlsen, Jacob Johnsen, Nichlas Riise Jespersen, Hans Erik Bøtker, Jens Erik Nielsen-Kudsk
BACKGROUND: To investigate whether modulation of the sGC-cGMP-PKG pathway protects against ischemia and reperfusion injury in the healthy and the failing right ventricle (RV). METHODS: Hearts from male Wistar rats with a healthy RV (n=39) or a hypertrophic and failing RV induced by pulmonary trunk banding (n=57) were isolated and perfused in a pressure-controlled modified Langendorff setup. The isolated hearts were randomized to control, ischemic preconditioning (IPC, 2×5min of global ischemia), a phosphodiesterase-5 (PDE5) inhibitor vardenafil (66nM) alone and in combination with a cGMP-dependent protein kinase (PKG) blocker KT 5823 (1μM)...
November 15, 2016: International Journal of Cardiology
A Bergeron, J P Aragon, C Guillemette, A Hébert, R Sullivan, P Blondin, F J Richard
The second messenger cyclic adenosine monophosphate (cAMP) has a central role in sperm physiology. Extracellular cAMP can be sequentially degraded into 5'AMP and adenosine by ecto-phosphodiesterases (ecto-PDE) and ecto-nucleotidases, a phenomenon called extracellular cAMP-adenosine pathway. As cAMP-adenosine pathway is involved in sperm capacitation, we hypothesize that extracellular PDEs are functionally present in seminal plasma. Exclusively measuring cAMP-PDE activity, total activity in bovine seminal plasma was 10...
August 27, 2016: Andrology
Haijun Deng, Dong Liu, Xiangming Mao, Xiaoliang Lan, Hao Liu, Guoxin Li
The current study sought to clarify the role of phosphodiesterase type 5 inhibitors (PDE-5i) and a vacuum erection device (VED) in penile rehabilitation after laparoscopic nerve-preserving radical proctectomy (LNRP) for rectal cancer. Participants were assigned to one of the following arms-no-intervention, nightly use of sildenafil 25 mg for 3 months after surgery, or concurrent use of nightly sildenafil 25 mg/day for 3 months and a vacuum erection device (VED) 10 to 15 minutes/day for 3 months-in a nonrandomized fashion...
August 24, 2016: American Journal of Men's Health
Fiori Alite, Neelam Balasubramanian, William Adams, Murat Surucu, Ibrahim Mescioglu, Matthew M Harkenrider
OBJECTIVES: Angiotensin-converting enzyme inhibitors (ACEi) have demonstrated decreased rates of radiation-induced lung injury in animal models and clinical reports have demonstrated decreased pneumonitis in the setting of conventionally fractionated radiation to the lung. We tested the role of ACEi in diminishing rates of symptomatic (grade ≥2) pneumonitis in the setting of lung stereotactic body radiation therapy (SBRT). METHODS: We analyzed patients treated with thoracic SBRT to 48 to 60 Gy in 4 to 5 fractions from 2006 to 2014...
August 24, 2016: American Journal of Clinical Oncology
Abdur Rauf, Ilkay Erdogan Orhan, Abdulselam Ertas, Hamdi Temel, Taibi Ben Hadda, Muhammad Saleem, Muslim Raza, Haroon Khan
Polyphenols are organic compounds widely found in plants and possess many diverse biological activities. In the current study, eleven polyphenolic compounds [rutin (1), trans-ferulic acid (2), epigallaocatechin gallate (3), fumaric acid (4), chlorogenic acid (5), gallic acid (6), trans-resveratrol (7), propyl gallate (8), (+)-catechin (9), quercetin (10), and kaempferol-3-O--D-galactoside (11)] have been evaluated for their in vitro inhibitory activity against phosphodiesterase-1 (PDE-1). The active compounds 1, 5, 6, and 7 possessed IC50 values of 173...
August 24, 2016: Current Topics in Medicinal Chemistry
Kátia R L Schwarz, Ramon Cesar Botigelli, Maite Del Collado, Fernanda Cavallari de Castro, Hugo Fernandes, Daniela M Paschoal, Cláudia Lima Verde Leal
Intracellular levels of cyclic nucleotides, such as cGMP, are involved in the regulation of adipocyte lipolysis. Cumulus-oocyte complexes (COCs) express enzymes that both synthesise (guanylate cyclase) and degrade (phosphodiesterase (PDE) 5A) cGMP. Because serum interferes with lipid metabolism, its effects on the cGMP pathway and lipid content in bovine COCs were examined. COCs were matured in medium containing fetal calf serum (FCS; 2% or 10%) or 0.4% bovine serum albumin (BSA; control). At both 2% and 10%, FCS decreased cGMP levels in COCs compared with BSA (0...
August 24, 2016: Reproduction, Fertility, and Development
Anna Krupa, Dorota Majda, Włodzimierz Mozgawa, Jakub Szlęk, Renata Jachowicz
The study provides the physicochemical characteristic of bosentan (BOS) in comparison to tadalafil (TA) and sildenafil citrate (SIL). Despite some reports dealing with thermal characteristic of SIL and TA, physicochemical properties of BOS have not been investigated so far. Recent clinical reports have indicated that the combination of bosentan and PDE-5 inhibitor can improve the effectiveness of pharmacotherapy of pulmonary arterial hypertension (PAH). However, in order to design personalized medicines for therapy of chronic rare diseases, detailed information on the thermal behaviour and solubility of each drug is indispensable...
August 5, 2016: AAPS PharmSciTech
Sattar Ostadhadi, Mohammad Ahangari, Vahid Nikoui, Abbas Norouzi-Javidan, Samira Zolfaghari, Farahnaz Jazaeri, Mohsen Chamanara, Reyhaneh Akbarian, Ahmad-Reza Dehpour
Lamotrigine is an anticonvulsant agent that shows clinical antidepressant properties. The aim of the present study was to investigate the involvement of N-methyl-d-aspartate (NMDA) receptors and nitric oxide-cyclic guanosine monophosphate (NO-cGMP) synthesis in possible antidepressant-like effect of lamotrigine in forced swimming test (FST) in mice. Intraperitoneal administration of lamotrigine (10mg/kg) decreased the immobility time in the FST (P<0.01) without any effect on locomotor activity in the open-field test (OFT), while higher dose of lamotrigine (30mg/kg) reduced the immobility time in the FST (P<0...
August 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
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