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Phosphodiesterase 5 inhibitors

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https://www.readbyqxmd.com/read/29440918/use-of-phosphodiesterase-type-5-inhibitors-and-risk-of-melanoma-a-meta-analysis-of-observational-studies
#1
Xinming Han, Yan Han, Yongsheng Zheng, Qiang Sun, Tao Ma, Li Dai, Junyi Zhang, Lianji Xu
Background: Phosphodiesterase type 5 inhibitor (PE5i) administration may stimulate the proliferation and survival of melanocytes. However, discrepancies remain regarding the association between PDE5i use and melanoma risk in observational studies in humans. Aim: To evaluate the association between PDE5i use and melanoma in a meta-analysis. Materials and methods: Studies were identified by searching the PubMed and Embase databases. A random-effects model was applied to synthesize the data...
2018: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29440309/the-phosphodiesterase-2a-inhibitor-tak-915-ameliorates-cognitive-impairments-and-social-withdrawal-in-n-methyl-d-aspartate-receptor-antagonist-induced-rat-models-of-schizophrenia
#2
Masato Nakashima, Haruka Imada, Eri Shiraishi, Yuki Ito, Noriko Suzuki, Maki Miyamoto, Takahiko Taniguchi, Hiroki Iwashita
The pathophysiology of schizophrenia has been associated with glutamatergic dysfunction. Modulation of the glutamatergic signaling pathway, including N-methyl-D-aspartate (NMDA) receptors, can provide a new therapeutic target for schizophrenia. Phosphodiesterase 2A (PDE2A) is highly expressed in the forebrain, and is a dual substrate enzyme that hydrolyzes both cAMP and cGMP, which play pivotal roles as intracellular second messengers downstream of NMDA receptors. Here we characterize the in vivo pharmacological profile of a selective and brain penetrant PDE2A inhibitor, (N-{(1S)-1-[3-fluoro-4-(trifluoromethoxy)phenyl]-2-methoxyethyl}-7-methoxy-2-oxo-2,3-dihydropyrido[2,3-b]pyrazine-4(1H)-carboxamide) (TAK-915) as a novel treatment for schizophrenia...
February 13, 2018: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29438488/cardioprotection-by-ischemic-postconditioning-and-cgmp-elevating-agents-involves-cardiomyocyte-nitric-oxide-sensitive-guanylyl-cyclase
#3
Sandra Frankenreiter, Dieter Groneberg, Anna Kuret, Thomas Krieg, Peter Ruth, Andreas Friebe, Robert Lukowski
Aims: It has been suggested that the nitric oxide-sensitive guanylyl cyclase (NO-GC)/cGMP-dependent signaling pathway affords protection against cardiac damage during acute myocardial infarction (AMI). It is, however, not clear whether the NO-GC/cGMP system confers its favorable effects through a mechanism located in cardiomyocytes (CMs). The aim of this study was to evaluate the infarct-limiting effects of the endogenous NO-GC in CMs in vivo. Methods and Results: Ischemia/reperfusion (I/R) injury was evaluated in mice with a cardiomyocyte-specific deletion of NO-GC (CM NO-GC KO) and in control siblings (CM NO-GC CTR) subjected to an in vivo model of AMI...
February 9, 2018: Cardiovascular Research
https://www.readbyqxmd.com/read/29436260/treatment-patterns-and-associated-health-care-costs-before-and-after-treatment-initiation-among-pulmonary-arterial-hypertension-patients-in-the-united-states
#4
Charles D Burger, A Burak Ozbay, Howard M Lazarus, Ellen Riehle, Leslie B Montejano, Gregory Lenhart, R James White
BACKGROUND: Despite multiple treatment options, the prognosis of pulmonary arterial hypertension (PAH) remains poor. PAH patients experience a high economic burden due to comorbidities, hospitalizations, and medication costs. Although combination therapy has been shown to reduce hospitalizations, the relationship between treatment, health care utilization, and costs remains unclear. OBJECTIVE: To provide a characterization of health care utilization and costs in real-world settings by comparing periods before and after initiating PAH-specific treatment...
February 13, 2018: Journal of Managed Care & Specialty Pharmacy
https://www.readbyqxmd.com/read/29434675/best-practice-in-the-management-of-storage-symptoms-in-male-lower-urinary-tract-symptoms-a-review-of-the-evidence-base
#5
REVIEW
Mauro Gacci, Arcangelo Sebastianelli, Pietro Spatafora, Giovanni Corona, Sergio Serni, Dirk De Ridder, Stavros Gravas, Paul Abrams
Storage lower urinary tract symptoms (LUTS) are characterized by an altered bladder sensation, increased daytime frequency, nocturia, urgency and urgency incontinence. Some evidence underlines the role of metabolic factors, pelvic ischemia, prostatic chronic inflammation and associated comorbidities in the pathophysiology of storage LUTS. A detailed evaluation of the severity of storage LUTS, and the concomitance of these symptoms with voiding and postmicturition symptoms, is mandatory for improving the diagnosis and personalizing treatment...
February 2018: Therapeutic Advances in Urology
https://www.readbyqxmd.com/read/29427285/effect-of-tadalafil-on-seizure-threshold-and-activity-of-antiepileptic-drugs-in-three-acute-seizure-tests-in-mice
#6
Katarzyna Socała, Dorota Nieoczym, Mateusz Pieróg, Elżbieta Wyska, Małgorzata Szafarz, Urszula Doboszewska, Piotr Wlaź
Tadalafil, a selective phosphodiesterase type 5 inhibitor, is a long-acting oral agent for the treatment of erectile dysfunction of multiple etiologies. Although generalized tonic-clonic seizures were reported in a healthy man after taking tadalafil, the influence of tadalafil on seizure susceptibility has not been studied so far. Therefore, the aim of the present study was to investigate the effect of tadalafil on seizure threshold as well as on the activity of some first- and second-generation antiepileptic drugs in three acute seizure tests in mice...
February 9, 2018: Neurotoxicity Research
https://www.readbyqxmd.com/read/29425663/sexual-rehabilitation-after-nerve-sparing-radical-prostatectomy-free-of-charge-phosphodiesterase-type-5-inhibitor-administration-improves-compliance-to-treatment
#7
Giampaolo Siena, Andrea Mari, Aude Canale, Nicola Mondaini, Andrea Chindemi, Isabella Greco, Omar Saleh, Sergio Serni, Giulio Nicita, Andrea Minervini, Marco Carini
BACKGROUND: In December 2006, the region of Tuscany (Italy) authorized the free-of-charge provision of phosphodiesterase type 5 inhibitors (PDE5I) for all patients with Tuscan citizenship who undergo nerve-sparing radical prostatectomy (NSRP). OBJECTIVE: To compare sexual rehabilitation outcomes in patients with low risk of erectile dysfunction and minimal comorbidities who received PDE5Is free of charge (PDE5I-F) with those who paid for PDE5Is (PDE5I-P) after bilateral NSRP...
February 2018: Journal of Sexual Medicine
https://www.readbyqxmd.com/read/29417763/combined-treatment-with-a-selective-pde10a-inhibitor-tak-063-and-either-haloperidol-or-olanzapine-at-subeffective-doses-produces-potent-antipsychotic-like-effects-without-affecting-plasma-prolactin-levels-and-cataleptic-responses-in-rodents
#8
Kazunori Suzuki, Akina Harada, Hirobumi Suzuki, Clizia Capuani, Annarosa Ugolini, Mauro Corsi, Haruhide Kimura
Activation of indirect pathway medium spiny neurons (MSNs) via promotion of cAMP production is the principal mechanism of action of current antipsychotics with dopamine D2 receptor antagonism. TAK-063 [1-[2-fluoro-4-(1H-pyrazol-1-yl)phenyl]-5-methoxy-3-(1-phenyl-1H-pyrazol-5-yl)pyridazin-4(1H)-one] is a novel phosphodiesterase 10A inhibitor that activates both direct and indirect pathway MSNs through increasing both cAMP and cGMP levels by inhibition of their degradation. The activation of indirect pathway MSNs through the distinct mechanism of action of these drugs raises the possibility of augmented pharmacological effects by combination therapy...
February 2018: Pharmacology Research & Perspectives
https://www.readbyqxmd.com/read/29417353/perioperative-management-with-phosphodiesterase-type-5-inhibitor-and-prostaglandin-e1-for-moderate-portopulmonary-hypertension-following-adult-to-adult-living-donor-liver-transplantation-a-case-report
#9
Takashi Onoe, Asuka Tanaka, Kohei Ishiyama, Kentaro Ide, Hirotaka Tashiro, Hideki Ohdan
BACKGROUND: Portopulmonary hypertension (PPH) is a relatively rare but well-recognized complication of end-stage liver disease. Moderate or severe PPH (mean pulmonary artery pressure [mPAP] ≥ 35 mmHg) is usually a contraindication for liver transplantation due to high operation-related mortality. Here, we report on a patient with moderate PPH whose condition was successfully managed with a phosphodiesterase type 5 (PDE5) inhibitor (tadalafil) and prostaglandin E1, who experienced rapid improvement of PPH after living-donor liver transplantation (LDLT)...
February 7, 2018: Surgical Case Reports
https://www.readbyqxmd.com/read/29409493/scrotal-hemorrhage-after-testicular-sperm-aspiration-may-be-associated-with-phosphodiesterase-5-inhibitor-administration-a-retrospective-study
#10
Yong-Tong Zhu, Rui Hua, Song Quan, Wan-Long Tan, Qing-Jun Chu, Chun-Yan Wang
BACKGROUND: Scrotal hemorrhage after testicular sperm aspiration (TESA) is uncommon in clinical operation. Phosphodiesterase-5 inhibitors (PDE5i) are commonly given to men who have difficulty providing a sperm sample for assisted reproductive technique such as in vitro fertilization. In this study, we examine the incidence of scrotal hemorrhage after TESA in men who received a PDE5i. METHODS: In this retrospective study, 504 men with TESA operation in Center for Reproductive Medicine, Nanfang Hospital, Southern Medical University were collected...
February 6, 2018: BMC Urology
https://www.readbyqxmd.com/read/29409064/randomised-trial-of-cpap-and-vardenafil-on-erectile-and-arterial-function-in-men-with-obstructive-sleep-apnea-and-erectile-dysfunction
#11
Kerri L Melehan, Camilla M Hoyos, Garun S Hamilton, Keith K Wong, Brendon J Yee, Rob I McLachlan, Shamus O'Meagher, David Celermajer, Martin K Ng, Ronald R Grunstein, Peter Y Liu
Context: Erectile function is important for life satisfaction and is often impaired in men with obstructive sleep apnea (OSA). Uncontrolled studies show that treating OSA with continuous positive airway pressure (CPAP) improves erectile function. Phosphodiesterase type 5 inhibitors (e.g. vardenafil) are the first-line therapy for erectile dysfunction (ED), but may worsen OSA. Objective: To assess the effects of CPAP and vardenafil on ED. Design: Sixty one men with moderate-to-severe OSA and ED were randomised to 12 weeks of CPAP or sham CPAP, and 10mg daily vardenafil or placebo, in a 2x2 factorial design...
February 1, 2018: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29407945/synthesis-and-biological-evaluation-of-pyridazinone-derivatives-as-potential-anti-inflammatory-agents
#12
Chantal Barberot, Aurélie Moniot, Ingrid Allart-Simon, Laurette Malleret, Tatiana Yegorova, Marie Laronze-Cochard, Abderrazzaq Bentaher, Maurice Médebielle, Jean-Philippe Bouillon, Eric Hénon, Janos Sapi, Frédéric Velard, Stéphane Gérard
Cyclic nucleotide phosphodiesterase type 4 (PDE4), that controls intracellular level of cyclic nucleotide cAMP, has aroused scientific attention as a suitable target for anti-inflammatory therapy in respiratory diseases. Here we describe the development of two families of pyridazinone derivatives as potential PDE4 inhibitors and their evaluation as anti-inflammatory agents. Among these derivatives, 4,5-dihydropyridazinone representatives possess promising activity, selectivity towards PDE4 isoenzymes and are able to reduce IL-8 production by human primary polymorphonuclear cells...
January 17, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29402732/female-sexual-dysfunction-a-systematic-review-of-outcomes-across-various-treatment-modalities
#13
REVIEW
James M Weinberger, Justin Houman, Ashley T Caron, Jennifer Anger
BACKGROUND: Female sexual dysfunction (FSD) is a highly prevalent condition. Nevertheless, the scientific literature has only recently begun to accumulate evidence for treatment modalities that address the underlying etiologies of FSD. AIM: The purpose of this systematic review is to elucidate what treatments are effective across the various symptom complexes of FSD. METHODS: Utilizing Meta-analysis of Observational Studies in Epidemiology guidelines, we conducted a systematic review of PubMed, EMBASE, clinicaltrials...
February 3, 2018: Sexual Medicine Reviews
https://www.readbyqxmd.com/read/29400443/in-vivo-characterization-of-two-18f-labeled-pde10a-pet-radioligands-in-nonhuman-primate-brains
#14
Hui Liu, Hongjun Jin, Zhonghua Luo, Xuyi Yue, Xiang Zhang, Hubert Flores, Yi Su, Joel S Perlmutter, Zhude Tu
PET with Phosphodiesterase 10A (PDE10A) specific radioligands provide a noninvasive and quantitative imaging tool to access the expression of this enzyme in vivo under normal and diseased conditions. We recently reported two potent 18F-labeled PDE10A radioligands (18F-TZ19106B and 18F-TZ8110); initial evaluation in rats and nonhuman primates indicated stable metabolic profiles and excellent target-to-non-target ratio (striatum/cerebellum) for both tracers. Herein, we focused on in vivo characterization of 18F-TZ19106B and 18F-TZ8110 to identify a suitable radioligand for imaging PDE10A in vivo...
February 5, 2018: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/29396020/low-intensity-shockwave-therapy-for-erectile-dysfunction-a-randomized-clinical-trial-comparing-2-treatment-protocols-and-the-impact-of-repeating-treatment
#15
Dimitrios Kalyvianakis, Evangelos Memmos, Ioannis Mykoniatis, Paraskevi Kapoteli, Dimitrios Memmos, Dimitrios Hatzichristou
BACKGROUND: There is lack of evidence-based optimization of the protocol for low-intensity shockwave therapy for erectile dysfunction. Furthermore, the safety and efficacy of repeating shockwave therapy have not been explored. AIM: To compare the efficacy and safety of 6 and 12 treatment sessions within a 6-week treatment period and investigate the effect of repeat treatment after a 6-month period in a 2-phase study. METHODS: Patients with vasculogenic erectile dysfunction that responded to phosphodiesterase type 5 inhibitors were randomized into 2 groups: low-intensity shockwave therapy sessions once (group A, n = 21) or twice (group B, n = 21) per week for 6 consecutive weeks (phase 1)...
January 27, 2018: Journal of Sexual Medicine
https://www.readbyqxmd.com/read/29395941/vardenafil-inhibiting-parasympathetic-function-of-tracheal-smooth-muscle
#16
Fei-Peng Lee, Pin-Zhir Chao, Hsing-Won Wang
BACKGROUND: Levitra, a phosphodiesterase-5 (PDE5) inhibitor, is the trade name of vardenafil. Nowadays, it is applied to treatment of erectile dysfunction. PDE5 inhibitors are employed to induce dilatation of the vascular smooth muscle. The effect of Levitra on impotency is well known; however, its effect on the tracheal smooth muscle has rarely been explored. When administered for sexual symptoms via oral intake or inhalation, Levitra might affect the trachea. METHODS: This study assessed the effects of Levitra on isolated rat tracheal smooth muscle by examining its effect on resting tension of tracheal smooth muscle, contraction caused by 10-6 M methacholine as a parasympathetic mimetic, and electrically induced tracheal smooth muscle contractions...
January 27, 2018: Journal of the Chinese Medical Association: JCMA
https://www.readbyqxmd.com/read/29394114/efficacy-of-newer-medications-for-lower-urinary-tract-symptoms-attributed-to-benign-prostatic-hyperplasia-a-systematic-review
#17
Roderick MacDonald, Michelle Brasure, Philipp Dahm, Carin M Olson, Victoria A Nelson, Howard A Fink, Michael C Risk, Bruce Rwabasonga, Timothy J Wilt
We conducted a systematic review to evaluate the efficacy and adverse effects of newer drugs used to treat lower urinary tract symptoms (LUTS). The drugs were either Food and Drug Administration (FDA) approved for benign prostatic hyperplasia (BPH) or not FDA approved for BPH but have been evaluated for treatment of BPH since 2008. We searched bibliographic databases through September 2017. We included randomized controlled trials (RCTs) lasting one month or longer published in English. Outcomes of interest were LUTS assessed by validated measures...
February 2, 2018: Aging Male: the Official Journal of the International Society for the Study of the Aging Male
https://www.readbyqxmd.com/read/29391766/beneficial-long-term-effect-of-a-phosphodiesterase-5-inhibitor-in-cirrhotic-portal-hypertension-a-case-report-with-8-years-follow-up
#18
Peter Deibert, Adhara Lazaro, Zoran Stankovic, Denise Schaffner, Martin Rössle, Wolfgang Kreisel
Non-selective beta-blockers are the mainstay of medical therapy for portal hypertension in liver cirrhosis. Inhibitors of phosphodiesterase-5 (PDE-5-inhibitors) reduce portal pressure in the acute setting by > 10% which may suggest a long-term beneficial effect. Currently, there is no available data on long-term treatment of portal hypertension with PDE-5-inhibitors. This case of a patient with liver cirrhosis secondary to autoimmune liver disease with episodes of bleeding from esophageal varices is the first documented case in which a treatment with a PDE-5-inhibitor for eight years was monitored...
January 21, 2018: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/29378485/treatment-of-lower-urinary-tract-symptoms-benign-prostatic-hyperplasia-and-erectile-dysfunction
#19
Aldo E Calogero, Giovanni Burgio, Rosita A Condorelli, Rossella Cannarella, Sandro La Vignera
This article summarizes years of challenging research on erectile dysfunction (ED), a condition that has an important social and cultural relevance. Preclinical and clinical research progress has led to new therapeutic approaches to ED in patients with different comorbidities and particularly in those with low urinary tract symptoms (LUTS)/benign prostatic hyperplasia (BPH). These goals were possible only by combined work of specialists and researchers of different and intertwined medical disciplines. Currently, tadalafil (5 mg/d) is the best choice; other phosphodiesterase-5 inhibitors (PDE5i) are not included among options, despite the growing evidence of therapeutic effects...
January 29, 2018: Aging Male: the Official Journal of the International Society for the Study of the Aging Male
https://www.readbyqxmd.com/read/29376615/-current-approaches-to-conservative-treatment-of-men-with-concomitant-benign-prostatic-hyperplasia-and-erectile-dysfunction
#20
A A Kamalov, A M Takhirzade
The article reviews the results of various conservative treatments for concomitant benign prostatic hyperplasia (BPH) and erectile dysfunction (ED). Phosphodiesterase type 5 (PDE5) inhibitors remain the first-line therapy for this category of patients taking into account their positive effect on both ED and BPH. The preferred treatment scheme includes PDE-5 inhibitor co-administered with 1-adrenoblocker. However, other combination treatments are considered promising, for example, a PDE-5 inhibitor with a 5-reductase inhibitor or a three-component treatment regimen: 1-adrenoblocker + 5-reductase inhibitor + PDE-5 inhibitor...
December 2017: Urologii︠a︡
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