phosphodiesterase inhibitors

Summary

Summary: Compounds which inhibit or antagonize the biosynthesis or actions of phosphodiesterases.

Top Publications

  1. ncbi Sildenafil citrate therapy for pulmonary arterial hypertension
    Nazzareno Galie
    Institute of Cardiology, University of Bologna, Bologna, Italy
    N Engl J Med 353:2148-57. 2005
  2. ncbi Effect of 1-year treatment with roflumilast in severe chronic obstructive pulmonary disease
    Peter M A Calverley
    Department of Medicine, Clinical Sciences, University Hospital Aintree, Liverpool L97AL, UK
    Am J Respir Crit Care Med 176:154-61. 2007
  3. ncbi Chronic inhibition of cyclic GMP phosphodiesterase 5A prevents and reverses cardiac hypertrophy
    Eiki Takimoto
    Division of Cardiology, Department of Medicine, Johns Hopkins Medical Institutions, Ross 835, 720 Rutland Avenue, Baltimore, Maryland 21205, USA
    Nat Med 11:214-22. 2005
  4. ncbi Dysregulation of protein kinase a signaling in the aged prefrontal cortex: new strategy for treating age-related cognitive decline
    Brian P Ramos
    Department of Neurobiology, Yale University School of Medicine, New Haven, CT 06510, USA
    Neuron 40:835-45. 2003
  5. ncbi Phosphodiesterase inhibitors: a novel mechanism for receptor-independent antipsychotic medications
    C R Maxwell
    Stanley Center for Experimental Therapeutics in Psychiatry, Division of Neuropsychiatry, Department of Psychiatry, University of Pennsylvania, Philadelphia, PA 19104, USA
    Neuroscience 129:101-7. 2004
  6. ncbi PDE4D plays a critical role in the control of airway smooth muscle contraction
    Celine Mehats
    Division of Reproductive Biology, Department of Obstetrics and Gynecology, Stanford University School of Medicine, 300 Pasteur Dr, Room A344, Stanford, California 94305 5317, USA
    FASEB J 17:1831-41. 2003
  7. pmc PDE4 inhibitors: current status
    D Spina
    King s College London School of Biomedical and Health Science, Pharmaceutical Science Research Division, Sackler Institute of Pulmonary Pharmacology, London, UK
    Br J Pharmacol 155:308-15. 2008
  8. pmc ERK phosphorylation mediates sildenafil-induced myocardial protection against ischemia-reperfusion injury in mice
    Anindita Das
    Division of Cardiology, Department of Internal Medicine, Box 980281, Virginia Commonwealth Univ Medical Center, 1101 East Marshall St, Rm 7 040, Richmond, VA 23298 0281, USA
    Am J Physiol Heart Circ Physiol 296:H1236-43. 2009
  9. ncbi Keynote review: phosphodiesterase-4 as a therapeutic target
    Miles D Houslay
    Division of Biochemistry and Molecular Biology, IBLS, Wolfson Link Building, University of Glasgow, University Avenue, Glasgow, G12 8QQ, Scotland, UK
    Drug Discov Today 10:1503-19. 2005
  10. pmc Hydrolysis products of cAMP analogs cause transformation of Trypanosoma brucei from slender to stumpy-like forms
    Sunil Laxman
    Department of Pharmacology, Division of Allergy and Infectious Diseases, University of Washington, Seattle, WA 98195, USA
    Proc Natl Acad Sci U S A 103:19194-9. 2006

Detail Information

Publications291 found, 100 shown here

  1. ncbi Sildenafil citrate therapy for pulmonary arterial hypertension
    Nazzareno Galie
    Institute of Cardiology, University of Bologna, Bologna, Italy
    N Engl J Med 353:2148-57. 2005
    ....
  2. ncbi Effect of 1-year treatment with roflumilast in severe chronic obstructive pulmonary disease
    Peter M A Calverley
    Department of Medicine, Clinical Sciences, University Hospital Aintree, Liverpool L97AL, UK
    Am J Respir Crit Care Med 176:154-61. 2007
    ..Whether treatment is effective in more severe COPD (GOLD [Global Initiative for Chronic Obstructive Lung Disease] stages III and IV) over a longer period is unknown...
  3. ncbi Chronic inhibition of cyclic GMP phosphodiesterase 5A prevents and reverses cardiac hypertrophy
    Eiki Takimoto
    Division of Cardiology, Department of Medicine, Johns Hopkins Medical Institutions, Ross 835, 720 Rutland Avenue, Baltimore, Maryland 21205, USA
    Nat Med 11:214-22. 2005
    ..PDE5A inhibition may provide a new treatment strategy for cardiac hypertrophy and remodeling...
  4. ncbi Dysregulation of protein kinase a signaling in the aged prefrontal cortex: new strategy for treating age-related cognitive decline
    Brian P Ramos
    Department of Neurobiology, Yale University School of Medicine, New Haven, CT 06510, USA
    Neuron 40:835-45. 2003
    ..These data demonstrate that PKA inhibition, rather than activation, is the appropriate strategy for restoring prefrontal cortical cognitive abilities in the elderly...
  5. ncbi Phosphodiesterase inhibitors: a novel mechanism for receptor-independent antipsychotic medications
    C R Maxwell
    Stanley Center for Experimental Therapeutics in Psychiatry, Division of Neuropsychiatry, Department of Psychiatry, University of Pennsylvania, Philadelphia, PA 19104, USA
    Neuroscience 129:101-7. 2004
    ..The current study examines the potential of using non-receptor-based agents that modify intracellular signal transduction as potential antipsychotic medications...
  6. ncbi PDE4D plays a critical role in the control of airway smooth muscle contraction
    Celine Mehats
    Division of Reproductive Biology, Department of Obstetrics and Gynecology, Stanford University School of Medicine, 300 Pasteur Dr, Room A344, Stanford, California 94305 5317, USA
    FASEB J 17:1831-41. 2003
    ..These results demonstrate that PDE4D plays a key role in balancing relaxant and contracting cues in airway smooth muscle, suggesting that natural mutations in the PDE4D gene have profound effects on airway tone...
  7. pmc PDE4 inhibitors: current status
    D Spina
    King s College London School of Biomedical and Health Science, Pharmaceutical Science Research Division, Sackler Institute of Pulmonary Pharmacology, London, UK
    Br J Pharmacol 155:308-15. 2008
    ..A number of strategies are currently being pursued in attempts to improve clinical efficacy and reduce side effects, including delivery via the inhaled route, and/or development of non-emetic PDE4 inhibitors and mixed PDE inhibitors...
  8. pmc ERK phosphorylation mediates sildenafil-induced myocardial protection against ischemia-reperfusion injury in mice
    Anindita Das
    Division of Cardiology, Department of Internal Medicine, Box 980281, Virginia Commonwealth Univ Medical Center, 1101 East Marshall St, Rm 7 040, Richmond, VA 23298 0281, USA
    Am J Physiol Heart Circ Physiol 296:H1236-43. 2009
    ..We conclude that these studies provide first direct evidence that PKG-dependent ERK phosphorylation is indispensable for the induction of eNOS/iNOS and Bcl-2 and the resulting cardioprotection by sildenafil...
  9. ncbi Keynote review: phosphodiesterase-4 as a therapeutic target
    Miles D Houslay
    Division of Biochemistry and Molecular Biology, IBLS, Wolfson Link Building, University of Glasgow, University Avenue, Glasgow, G12 8QQ, Scotland, UK
    Drug Discov Today 10:1503-19. 2005
    ..Here, we delineate the range of PDE4 isoforms, their role in signaling, their structural biology and related preclinical and clinical pharmacology...
  10. pmc Hydrolysis products of cAMP analogs cause transformation of Trypanosoma brucei from slender to stumpy-like forms
    Sunil Laxman
    Department of Pharmacology, Division of Allergy and Infectious Diseases, University of Washington, Seattle, WA 98195, USA
    Proc Natl Acad Sci U S A 103:19194-9. 2006
    ..These data suggest that the slender-to-stumpy transformation of T. brucei may not be mediated directly by cAMP and also raise the possibility of using such adenosine analogs as antitrypanosomal drugs...
  11. ncbi Genistein stimulates electrogenic Cl- secretion via phosphodiesterase modulation in the mouse jejunum
    Pin Chun Chao
    Dept of Physiology, School of Medical Sciences, Univ of Otago, P O Box 913, Dunedin, New Zealand
    Am J Physiol Cell Physiol 297:C688-98. 2009
    ..Likewise, H89 reduced the genistein-stimulated I(sc). Here, we demonstrate, for the first time, that genistein activates Cl(-) secretion of the mouse jejunum via inhibition of a PDE3-dependent pathway...
  12. pmc Dual PDE3/4 inhibitors as therapeutic agents for chronic obstructive pulmonary disease
    Katharine H Banner
    Novartis Institute for Biomedical Research, Horsham, West Sussex, RH12 5AB, UK
    Br J Pharmacol 157:892-906. 2009
    ....
  13. ncbi Effect of sildenafil on the anticonvulsant action of classical and second-generation antiepileptic drugs in maximal electroshock-induced seizures in mice
    Dorota Nieoczym
    Department of Animal Physiology, Institute of Biology, Maria Curie Skłodowska University, Lublin, Poland
    Epilepsia 51:1552-9. 2010
    ....
  14. ncbi Exploiting cGMP-based therapies for the prevention of left ventricular hypertrophy: NO* and beyond
    Rebecca H Ritchie
    Heart Failure Pharmacology, Baker IDI Heart and Diabetes Institute Melbourne, Victoria, Australia
    Pharmacol Ther 124:279-300. 2009
    ..ligands of the cGMP-generating enzymes, soluble (sGC) and particulate guanylyl cyclases (pGC), and phosphodiesterase inhibitors. Further impact of cGMP within the cardiovascular system is also discussed with a view to representing ..
  15. pmc Sildenafil increases chemotherapeutic efficacy of doxorubicin in prostate cancer and ameliorates cardiac dysfunction
    Anindita Das
    Division of Cardiology, Department of Internal Medicine, Virginia Commonwealth University Pauley Heart Center, Richmond, VA 23298, USA
    Proc Natl Acad Sci U S A 107:18202-7. 2010
    ..In conclusion, these results provide provocative evidence that sildenafil is both a powerful sensitizer of DOX-induced killing of prostate cancer while providing concurrent cardioprotective benefit...
  16. ncbi Selective PDE inhibitors as novel treatments for respiratory diseases
    Clive P Page
    Sackler Institute of Pulmonary Pharmacology, Institute of Pharmaceutical Science, Franklin Wilkins Building, King s College London, London SE1 9NH, UK
    Curr Opin Pharmacol 12:275-86. 2012
    ....
  17. ncbi cGMP modulates stem cells differentiation to neurons in brain in vivo
    U Gomez-Pinedo
    Laboratorio de Morfologia Celular, Centro de Investigacion Principe Felipe, Avda Autopista del Saler, Valencia, Spain
    Neuroscience 165:1275-83. 2010
    ..These results support that cGMP modulates the fate of neural stem cells in brain in vivo and suggest that high cGMP levels promote its differentiation to neurons while reduced cGMP levels promote differentiation to non-neuronal cells...
  18. pmc Persistent improvement in synaptic and cognitive functions in an Alzheimer mouse model after rolipram treatment
    Bing Gong
    The Center for Dementia Research, Nathan Kline Institute for Psychiatric Research, Orangeburg, New York, USA
    J Clin Invest 114:1624-34. 2004
    ..Thus, agents that enhance the cAMP/PKA/CREB pathway have potential for the treatment of AD and other diseases associated with elevated Abeta42 levels...
  19. pmc Phosphodiesterase 4 and phosphatase 2A differentially regulate cAMP/protein kinase a signaling for cardiac myocyte contraction under stimulation of beta1 adrenergic receptor
    Vania De Arcangelis
    Department of Molecular and Integrative Physiology, University of Illinois at Urbana Champaign, Urbana, IL 61801, USA
    Mol Pharmacol 74:1453-62. 2008
    ..Therefore, PP2A plays a key role in limiting PKA phosphorylation of phospholamban and TnI for myocyte contraction responses under beta(1)AR stimulation...
  20. pmc Insights into the regulation of TNF-alpha production in human mononuclear cells: the effects of non-specific phosphodiesterase inhibition
    Jessica Deree
    Department of Trauma and Critical Care, University of California San Diego Medical Center, San Diego, CA, USA
    Clinics (Sao Paulo) 63:321-8. 2008
    ....
  21. ncbi Regulation of neurogenesis in adult mouse hippocampus by cAMP and the cAMP response element-binding protein
    Shin Nakagawa
    Division of Molecular Psychiatry, Abraham Ribicoff Research Facilities, Connecticut Mental Health Center, Yale University School of Medicine, New Haven, Connecticut 06508, USA
    J Neurosci 22:3673-82. 2002
    ..The results suggest that the cAMP-CREB cascade could contribute to the actions of neurotransmitters and neurotrophic factors on adult neurogenesis...
  22. ncbi Randomized trial of phosphodiesterase inhibitors versus catecholamines in patients with acutely decompensated heart failure
    A Kawamura
    Department of Medicine, Keio University School of Medicine, Tokyo, Japan
    Jpn Circ J 65:858-62. 2001
    ..The present study was designed to test the hypothesis that phosphodiesterase inhibitors, but not catecholamines, could favorably affect neurohormone and cytokine profiles in patients with ..
  23. ncbi Phosphodiesterase inhibitors for cognitive enhancement
    Gregory M Rose
    Memory Pharmaceuticals Corp, 100 Philips Parkway, Montvale, NJ 07645, USA
    Curr Pharm Des 11:3329-34. 2005
    ....
  24. ncbi Cyclic nucleotide phosphodiesterases: molecular regulation to clinical use
    Andrew T Bender
    Department of Pharmacology, University of Washington Medical School, Health Sciences Building, Box 357280, Seattle, WA 98195 7280, USA
    Pharmacol Rev 58:488-520. 2006
    ..PDEs hold great promise as drug targets and recent research advances make this an exciting time for the field of PDE research...
  25. pmc PARP1 gene knock-out increases resistance to retinal degeneration without affecting retinal function
    Ayse Sahaboglu
    Division of Experimental Ophthalmology, Institute for Ophthalmic Research, University of Tubingen, Tubingen, Germany
    PLoS ONE 5:e15495. 2010
    ..Moreover, our results suggest that PARP dependent cell death or PARthanatos may play a major role in retinal degeneration and highlight the possibility to use specific PARP inhibitors for the treatment of RP...
  26. ncbi Constitutive phosphodiesterase activity restricts spontaneous beating rate of cardiac pacemaker cells by suppressing local Ca2+ releases
    Tatiana M Vinogradova
    Laboratory of Cardiovascular Science, Gerontology Research Center, NIA, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 6825, USA
    Circ Res 102:761-9. 2008
    ....
  27. ncbi Chronic administration of Sildenafil improves markers of endothelial function in men with Type 2 diabetes
    A Aversa
    Department of Medical Pathophysiology, Sapienza University of Rome, Rome, Italy
    Diabet Med 25:37-44. 2008
    ..The aim of this study was to determine the effects of chronic therapy with sildenafil on endothelial function in patients with Type 2 diabetes mellitus (DM2)...
  28. ncbi Cilostazol inhibits cytokine-induced nuclear factor-kappaB activation via AMP-activated protein kinase activation in vascular endothelial cells
    Yoshiyuki Hattori
    Department of Endocrinology and Metabolism, Dokkyo University School of Medicine, Mibu, Tochigi 321 0293, Japan
    Cardiovasc Res 81:133-9. 2009
    ..We hypothesized that cilostazol may prevent inflammatory cytokine induced-nuclear factor (NF)-kappaB activation by activating AMP-activated protein kinase (AMPK) in vascular endothelial cells...
  29. ncbi Versatile effects of sildenafil: recent pharmacological applications
    Subramaniam Uthayathas
    Division of Pharmacology and Toxicology, Depertment of Pharmacal Sciences, Harrison School of Pharmacy, Auburn University, Auburn, AL 36849, USA
    Pharmacol Rep 59:150-63. 2007
    ..The present review primarily focuses on the various pharmacological effects of sildenafil with regard to its influence on the nervous and pulmonary system...
  30. pmc Deletion of phosphodiesterase 4D in mice shortens alpha(2)-adrenoceptor-mediated anesthesia, a behavioral correlate of emesis
    Annette Robichaud
    Merck Frosst Centre for Therapeutic Research, Pointe Claire Dorval, Quebec, Canada
    J Clin Invest 110:1045-52. 2002
    ..These findings strongly support the hypothesis that inhibition of PDE4D is pivotal to the anesthesia-reversing effect of PMNPQ and is likely responsible for emesis induced by PDE4 inhibitors...
  31. ncbi Cardiac phosphodiesterase 5 (cGMP-specific) modulates beta-adrenergic signaling in vivo and is down-regulated in heart failure
    H Senzaki
    Division of Cardiology, Department of Medicine, Johns Hopkins Medical Institutions, Baltimore, Maryland 21287, USA
    FASEB J 15:1718-26. 2001
    ....
  32. ncbi Phosphodiesterases in the CNS: targets for drug development
    Frank S Menniti
    Pfizer Global Research and Development, CNS Discovery, Groton, Connecticut 06340, USA
    Nat Rev Drug Discov 5:660-70. 2006
    ..In this article, we review the current state of the art in the burgeoning field of phosphodiesterase pharmacology in the CNS...
  33. ncbi COPD: current therapeutic interventions and future approaches
    P J Barnes
    National Heart and Lung Institute, Imperial College School of Medicine, Dovehouse St, London SW3 6LY, UK
    Eur Respir J 25:1084-106. 2005
    ..More research is needed to understand the cellular and molecular mechanisms of chronic obstructive pulmonary disease and to develop biomarkers and monitoring techniques to aid the development of new therapies...
  34. pmc Regulator of G protein signaling 2 mediates cardiac compensation to pressure overload and antihypertrophic effects of PDE5 inhibition in mice
    Eiki Takimoto
    Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
    J Clin Invest 119:408-20. 2009
    ..Thus, RGS2 is required for early myocardial compensation to pressure overload and mediates the initial antihypertrophic and cardioprotective effects of PDE5 inhibitors...
  35. ncbi Sildenafil-associated nonarteritic anterior ischemic optic neuropathy
    Howard D Pomeranz
    Department of Ophthalmology, University of Minnesota Medical School, MMC 493, 420 Delaware Street SE, Minneapolis, MN 55455 0501, USA
    Ophthalmology 109:584-7. 2002
    ..To describe the clinical features of five patients who developed nonarteritic anterior ischemic optic neuropathy (NAION) after ingestion of sildenafil citrate (Viagra; Pfizer Pharmaceuticals, New York, NY)...
  36. ncbi Fluorescence resonance energy transfer-based analysis of cAMP dynamics in live neonatal rat cardiac myocytes reveals distinct functions of compartmentalized phosphodiesterases
    Marco Mongillo
    Dulbecco Telethon Institute, Padova, Italy
    Circ Res 95:67-75. 2004
    ..PDE3 and PDE4 localize to distinct compartments and this may underpin their different functional roles. Our findings indicate the importance of distinctly localized PDE isoenzymes in determining compartmentalized cAMP signaling...
  37. ncbi Sildenafil (Viagra) induces neurogenesis and promotes functional recovery after stroke in rats
    Ruilan Zhang
    Department of Neurology, Henry Ford Health Sciences Center, Detroit, Mich, USA
    Stroke 33:2675-80. 2002
    ..We tested the hypothesis that sildenafil, a phosphodiesterase type 5 (PDE5) inhibitor, promotes functional recovery and neurogenesis after stroke...
  38. pmc Differential effects of non-selective and selective phosphodiesterase inhibitors on human eosinophil functions
    A Hatzelmann
    Byk Gulden, Department of Biochemistry, Konstanz, Germany
    Br J Pharmacol 114:821-31. 1995
    ....
  39. pmc PDE1 isozymes, key regulators of pathological vascular remodeling
    Stefan Chan
    Department of Pharmacology and Physiology, Aab Cardiovascular Research Institute, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, United States
    Curr Opin Pharmacol 11:720-4. 2011
    ..This review summarizes the work done to characterize the role and therapeutic potential of PDE1 isozymes in pathological vascular remodeling...
  40. pmc Pharmacological validation of Trypanosoma brucei phosphodiesterases as novel drug targets
    Harry P de Koning
    Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, United Kingdom
    J Infect Dis 206:229-37. 2012
    ..Cpd A prevents cytokinesis, resulting in multinucleated, multiflagellated cells that eventually lyse. These observations pharmacologically validate the highly conserved trypanosomal PDEs as potential drug targets...
  41. ncbi Discrete microdomains with high concentration of cAMP in stimulated rat neonatal cardiac myocytes
    Manuela Zaccolo
    Department of Biomedical Sciences and Venetian Institute for Molecular Medicine, University of Padua, Via Orus 2, 35129 Padua, Italy
    Science 295:1711-5. 2002
    ..Furthermore, we demonstrate that such gradients of cAMP specifically activate a subset of protein kinase A molecules anchored in proximity to the T tubule...
  42. ncbi Effect of nightly versus on-demand vardenafil on recovery of erectile function in men following bilateral nerve-sparing radical prostatectomy
    Francesco Montorsi
    Division of Urology, Universita Vita Salute San Raffaele, Via Olgettina 60, Milan, Italy
    Eur Urol 54:924-31. 2008
    ....
  43. ncbi Functional recovery in aged and young rats after embolic stroke: treatment with a phosphodiesterase type 5 inhibitor
    Li Zhang
    Department of Neurology, Henry Ford Health Sciences Center, Detroit, Mich, USA
    Stroke 36:847-52. 2005
    ..Here, we test the hypothesis that sildenafil provides restorative therapeutic benefit to the aged animal...
  44. ncbi Antiproliferative effect of sildenafil on human pulmonary artery smooth muscle cells
    Benedetta Tantini
    Department of Biochemistry, G Moruzzi University of Bologna, Bologna, Italy
    Basic Res Cardiol 100:131-8. 2005
    ..We conclude that sildenafil exerts an antiproliferative effect on human PASMC that is mediated by an interaction between the cGMP-PKG and the cAMP-PKA activated pathways, leading to inhibition of PDGF-mediated activation of the ERK...
  45. ncbi Phosphodiesterase inhibitors as anti-cancer drugs
    Liron Hirsh
    Department of Molecular Cell Biology, The Weizmann Institute of Science, Rehovot 76100, Israel
    Biochem Pharmacol 68:981-8. 2004
    ..A clinical trial, using theophylline as an anti-cancer drug, is currently being conducted in lung cancer patients...
  46. ncbi Long-term continuous sildenafil treatment ameliorates corporal veno-occlusive dysfunction (CVOD) induced by cavernosal nerve resection in rats
    I Kovanecz
    LA Biomedical Research Institute at Harbor UCLA Medical Center, Urology Research Laboratory, Torrance, CA 90502 2064, USA
    Int J Impot Res 20:202-12. 2008
    ....
  47. ncbi Phosphodiesterase-5 inhibition with sildenafil attenuates cardiomyocyte apoptosis and left ventricular dysfunction in a chronic model of doxorubicin cardiotoxicity
    Patrick W Fisher
    Department of Internal Medicine, Division of Cardiology, Virginia Commonwealth University Medical Center, Richmond 23298, USA
    Circulation 111:1601-10. 2005
    ..It is unclear whether sildenafil would provide similar protection from doxorubicin-induced cardiotoxicity...
  48. ncbi Theophylline in chronic obstructive pulmonary disease: new horizons
    Peter J Barnes
    Department of Thoracic Medicine, National Heart and Lung Institute, Imperial College, Dovehouse Street, London SW3 6LY, UK
    Proc Am Thorac Soc 2:334-9; discussion 340-1. 2005
    ..Better understanding of the molecular basis for the action of theophylline might lead to the development of novel drugs...
  49. ncbi Sildenafil preserves intracorporeal smooth muscle after radical retropubic prostatectomy
    Eric J Schwartz
    Division of Urology, University of Connecticut Health Sciences Center, Farmington, USA
    J Urol 171:771-4. 2004
    ..We assessed the effect of sildenafil on SM content after RRP...
  50. ncbi The flavonoid dioclein is a selective inhibitor of cyclic nucleotide phosphodiesterase type 1 (PDE1) and a cGMP-dependent protein kinase (PKG) vasorelaxant in human vascular tissue
    Roberta L Gonçalves
    Department of Physiology and Biophysics, ICB, Federal University of Minas Gerais, Belo Horizonte, Brazil
    Eur J Pharmacol 620:78-83. 2009
    ..Furthermore, dioclein may represent a new archetype to develop more specific PDE1 inhibitors...
  51. ncbi Cilostazol in the management of atherosclerosis
    Fabrizio Sallustio
    Department of Neuroscience, Stroke Unit, University of Tor Vergata, 00133 Rome, Italy
    Curr Vasc Pharmacol 8:363-72. 2010
    ..This review will focus on the pharmacological properties of cilostazol and its use in the management of atherothrombotic vascular diseases...
  52. ncbi Effects of phosphodiesterase inhibitors on tension induced by norepinephrine and accumulation of cyclic nucleotides in isolated human prostatic tissue
    Stefan Uckert
    Department of Urology, Hannover Medical School, Hannover, Germany
    Urology 71:526-30. 2008
    ....
  53. ncbi Treatment of Peyronie's disease with PDE5 inhibitors: an antifibrotic strategy
    Nestor F Gonzalez-Cadavid
    Department of Urology, David Geffen School of Medicine at UCLA, and Los Angeles Biomedical Research Institute LABioMed at Harbor UCLA Medical Center, Building F 6, 1124 West Carson Street, Torrance, CA 90502, USA
    Nat Rev Urol 7:215-21. 2010
    ....
  54. ncbi The preclinical pharmacology of roflumilast--a selective, oral phosphodiesterase 4 inhibitor in development for chronic obstructive pulmonary disease
    Armin Hatzelmann
    Nycomed GmbH, Konstanz, Germany
    Pulm Pharmacol Ther 23:235-56. 2010
    ..This enables roflumilast to offer effective, oral maintenance treatment for COPD, with an acceptable tolerability profile and the potential to favourably affect the extrapulmonary effects of the disease...
  55. ncbi Effects of sildenafil on pentylenetetrazol-induced convulsions in mice and amygdala-kindled seizures in rats
    Dorota Nieoczym
    Department of Animal Physiology, Institute of Biology, Maria Curie Skłodowska University, Akademicka 19, PL 20 033 Lublin, Poland
    Pharmacol Rep 62:383-91. 2010
    ..Based on these data and in view of the clinical observations, sildenafil should be used in patients suffering from epilepsy with caution and only based on a careful individual risk/benefit evaluation...
  56. ncbi Chronic administration of phosphodiesterase 5 inhibitor improves erectile and endothelial function in a rat model of diabetes
    Gook Jun Ahn
    Research Institutes, Dong A Pharmaceutical Company, 47 5 Sanggal, Kiheung, Youngin, Kyunggi 449 905, Korea
    Int J Androl 28:260-6. 2005
    ..55 fmol/mL, respectively, p < 0.05). These results demonstrate that chronic administration of DA-8159 could attenuate the development of the ED in diabetes and its effect is associated with an improvement in the endothelial function...
  57. pmc Phosphodiesterases and cardiac cGMP: evolving roles and controversies
    Manling Zhang
    Division of Cardiology, Department of Medicine, Johns Hopkins University Medical Institutions, Baltimore, MD, USA
    Trends Pharmacol Sci 32:360-5. 2011
    ..In this review we discuss recent research findings and controversies regarding the PDE/cGMP/PKG signaling pathway, and suggest directions for further research...
  58. pmc Can the anti-inflammatory potential of PDE4 inhibitors be realized: guarded optimism or wishful thinking?
    M A Giembycz
    Department of Pharmacology and Therapeutics, Institute of Infection, Immunity and Inflammation, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada
    Br J Pharmacol 155:288-90. 2008
    ....
  59. ncbi PDE4 inhibitors: a review of current developments (2005 - 2009)
    Lluís Pagès
    Almirall R and D Centre, Department of Medicinal Chemistry, Laurea Miro 408 410, 08980 Sant Feliu de Llobregat, Barcelona, Spain
    Expert Opin Ther Pat 19:1501-19. 2009
    ..Despite the sound preclinical database and some promising data from clinical trials, development of PDE4 inhibitors for the treatment of inflammatory or neurological diseases has been hampered by dose-limiting class-related side effects...
  60. ncbi Phosphodiesterase inhibitors in airways disease
    Kian Fan Chung
    National Heart and Lung Institute, Imperial College, Dovehouse St, London SW3, UK
    Eur J Pharmacol 533:110-7. 2006
    ..A dual PDE3-PDE4 compound may provide more bronchodilator and bronchoprotective effect in addition to the beneficial PDE4 effects...
  61. ncbi Phosphodiesterase-4 inhibitors in the treatment of inflammatory lung disease
    Domenico Spina
    The Sackler Institute of Pulmonary Pharmacology, GKT School of Biomedical Science, King s College London, London, UK
    Drugs 63:2575-94. 2003
    ..While cilomilast and roflumilast have low emetic potential they are not free from emesis and various strategies are being investigated in the hope of developing a PDE4 inhibitor without this adverse effect...
  62. pmc Selective phosphodiesterase inhibitors: a promising target for cognition enhancement
    Olga A H Reneerkens
    Department of Neuroscience, Faculty of Health, Medicine and Life Sciences, School for Mental Health and Neuroscience, Maastricht University, P O Box 616, 6200 MD Maastricht, The Netherlands
    Psychopharmacology (Berl) 202:419-43. 2009
    ..However, recently phosphodiesterases (PDEs) have gained increased attention as a potential new target for cognition enhancement. Inhibition of PDEs increases the intracellular availability of the second messengers cGMP and/or cAMP...
  63. ncbi Adenosine receptors and phosphodiesterase inhibitors stimulate Cl- secretion in Calu-3 cells
    Bryan R Cobb
    Department of Human Genetics, Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham, 35233, USA
    Am J Respir Cell Mol Biol 29:410-8. 2003
    We investigated cystic fibrosis transmembrane conductance regulator (CFTR) activation by clinically used phosphodiesterase inhibitors (PDEis) in Calu-3 cell monolayers alone and in combination with A2B adenosine receptor stimulation...
  64. ncbi Modulating effects of nonselective and selective phosphodiesterase inhibitors on lymphocyte subsets and humoral immune response in mice
    Marianna Szczypka
    Department of Biochemistry, Pharmacology and Toxicology, Faculty of Veterinary Medicine, Wrocław University of Environmental and Life Sciences, Norwida 31, PL 50 375 Wrocław, Poland
    Pharmacol Rep 62:1148-58. 2010
    ..No effect or slight influence of the drugs on anti-SRBC hemagglutinins was observed, but the number of plaque-forming splenocytes was increased. The drugs under investigation did not show a significant immunosuppressive effect...
  65. ncbi Group VIA calcium-independent phospholipase A2 mediates endothelial cell S phase progression
    Shane P Herbert
    Faculty of Biological Sciences, Institute of Molecular and Cellular Biology, University of Leeds, Leeds LS2 9JT, United Kingdom
    J Biol Chem 281:35709-16. 2006
    ..Consequently, iPLA2-VIA is a novel regulator of endothelial cell S phase progression, cell cycle residence, and angiogenesis...
  66. ncbi Immunomodulatory properties of pentoxifylline are mediated via adenosine-dependent pathways
    Simone Kreth
    Department of Anaesthesiology, Ludwig Maximilians University, Munich, Germany
    Shock 34:10-6. 2010
    ..Sufficient adenosine levels might be a prerequisite for the accessibility of sepsis patients to treatment with PTX...
  67. ncbi Selective phosphodiesterase-4 inhibitors in chronic obstructive lung disease
    Francisco J Soto
    Division of Pulmonary and Critical Care Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA
    Curr Opin Pulm Med 11:129-34. 2005
    ..Novel anti-inflammatory therapies such as selective phosphodiesterase 4 (PDE4) inhibitors are in clinical development. Their potential role in the management of COPD is described in this review...
  68. ncbi Crystal structure of phosphodiesterase 4D and inhibitor complex(1)
    Mi Eun Lee
    Department of Chemistry, Korea Advanced Institute of Science and Technology, 373 1 Kusong Dong, Yusong gu, Daejon 305 701, South Korea
    FEBS Lett 530:53-8. 2002
    ..Mutations of R358D or D322R among these interface residues prohibit dimerization of the PDE4D catalytic domain in solution...
  69. ncbi CODES, a novel procedure for ligand-based virtual screening: PDE7 inhibitors as an application example
    Ana Castro
    Instituto de Quimica Medica CSIC, Juan de la Cierva 3, Madrid, Spain
    Eur J Med Chem 43:1349-59. 2008
    ....
  70. ncbi Roflumilast, a phosphodiesterase 4 inhibitor, reduces airway hyperresponsiveness after allergen challenge
    C Louw
    Internal Medicine, Lung and Allergy Unit, University of Stellenbosch, School of Medicine, Cape Town, South Africa
    Respiration 74:411-7. 2007
    ..Roflumilast, an oral, once-daily phosphodiesterase 4 inhibitor, is currently in clinical development for the treatment of asthma...
  71. pmc Potential role of phosphodiesterase 7 in human T cell function: comparative effects of two phosphodiesterase inhibitors
    A Nakata
    Discovery Research Laboratory, Tanabe Seiyaku Co Ltd, Saitama, Japan
    Clin Exp Immunol 128:460-6. 2002
    ..PDE7 may play a critical role in the regulation of human T cell function, and thereby selective PDE7 inhibitors have the potential to be used to treat immunological and inflammatory disorders...
  72. ncbi Preclinical characterization of selective phosphodiesterase 10A inhibitors: a new therapeutic approach to the treatment of schizophrenia
    C J Schmidt
    Neuroscience, Pfizer Global Research and Development, Pfizer, Inc, Eastern Point Road, Groton, CT 06340, USA
    J Pharmacol Exp Ther 325:681-90. 2008
    ..These new pharmacological tools enabled studies that provide further evidence that inhibition of PDE10A represents an important new target for the treatment of schizophrenia and related disorders of basal ganglia function...
  73. ncbi Spatiotemporal dynamics of beta-adrenergic cAMP signals and L-type Ca2+ channel regulation in adult rat ventricular myocytes: role of phosphodiesterases
    Jérôme Leroy
    INSERM U 769, Universite Paris Sud 11, Faculte de Pharmacie, 5, rue J B Clement, F 92296 Chatenay Malabry Cedex, France
    Circ Res 102:1091-100. 2008
    ..These results reveal temporally distinct beta-adrenergic receptor cAMP compartments in ARVMs and shed new light on the intricate roles of PDE3 and PDE4...
  74. pmc Synthesis, structural analysis, and biological evaluation of thioxoquinazoline derivatives as phosphodiesterase 7 inhibitors
    Tania Castaño
    Instituto de Quimica Medica CSIC, Juan de la Cierva 3, 28006 Madrid, Spain
    ChemMedChem 4:866-76. 2009
    ..This structure, together with molecular modeling, provides insight into the selectivity of the PDE inhibitors and a template for the discovery of new PDE7 or PDE7/PDE4 dual inhibitors...
  75. pmc Pharmacokinetic and pharmacodynamic profile following oral administration of the phosphodiesterase (PDE)4 inhibitor V11294A in healthy volunteers
    Donna Donigi Gale
    Purdue Frederick Inc, Norwalk, CT, USA
    Br J Clin Pharmacol 54:478-84. 2002
    ..To assess the pharmacokinetic and pharmacodynamic profile of the novel PDE4 inhibitor V11294A (3-(3-cyclopentyloxy-4-methoxybenzyl)-6-ethylamino-8-isopropyl-3H purine hydrochloride) in healthy male volunteers...
  76. ncbi Is up-regulation of phosphodiesterase 4 activity by PGE2 involved in the desensitization of beta-mimetics in late pregnancy human myometrium?
    C Mehats
    INSERM, U 361, Maternité Port Royal Hopital Cochin, Universite Rene Descartes, 75014 Paris, France
    J Clin Endocrinol Metab 86:5358-65. 2001
    ..Accordingly, coapplication of a selective PDE4 inhibitor might greatly improve the usefulness of beta-mimetic in tocolysis...
  77. ncbi Phosphatidylcholine-specific phospholipase C activation in epithelial ovarian cancer cells
    Francesca Spadaro
    Section of Molecular and Cellular Imaging, Department of Cell Biology and Neurosciences, Istituto Superiore di Sanita, Rome, Italy
    Cancer Res 68:6541-9. 2008
    ..These findings warrant further investigations on the role of PC-PLC and on the effects of its inhibition on the pathways responsible for constitutive EOC cell stimulation and cell proliferation...
  78. ncbi Cyclic nucleotide phosphodiesterase (PDE) superfamily: a new target for the development of specific therapeutic agents
    Claire Lugnier
    CNRS UMR, 7034, Pharmacologie et Physicochimie des Interactions Moléculaires et Cellulaires, Faculte de Pharmacie, Universite Louis Pasteur de Strasbourg, 74 route du Rhin, BP 60024, 67401 Illkirch, France
    Pharmacol Ther 109:366-98. 2006
    ....
  79. ncbi Highly selective phosphodiesterase 4 inhibitors for the treatment of allergic skin diseases and psoriasis
    Wolfgang Baumer
    Department of Pharmacology, Toxicology, and Pharmacy, University of Veterinary Medicine Hannover, Foundation, D 30559 Hannover, Germany
    Inflamm Allergy Drug Targets 6:17-26. 2007
    ..AWD 12-281 (GW 842470) is currently under clinical evaluation for the topical treatment of atopic dermatitis. Results concerning clinical efficacy of this potent and selective PDE4 inhibitor are anxiously awaited...
  80. ncbi The second Princeton consensus on sexual dysfunction and cardiac risk: new guidelines for sexual medicine
    Graham Jackson
    Cardiothoracic Center, St Thomas Hospital, London, UK
    J Sex Med 3:28-36; discussion 36. 2006
    ..The first Princeton Consensus Conference (Princeton I) in 1999 developed guidelines for safe management of cardiac patients regarding sexual activity and the treatment of ED...
  81. ncbi Roflumilast attenuates pulmonary inflammation upon segmental endotoxin challenge in healthy subjects: a randomized placebo-controlled trial
    Jens M Hohlfeld
    Department of Clinical Airway Research, Fraunhofer Institute of Toxicology and Experimental Medicine ITEM, Nikolai Fuchs Street 1A, D 30625 Hannover, Germany
    Pulm Pharmacol Ther 21:616-23. 2008
    ..Roflumilast, an investigational, targeted phosphodiesterase 4 inhibitor, reduces the in vitro and in vivo inflammatory activity of cells such as neutrophils, eosinophils, macrophages, and monocytes...
  82. ncbi Inhibition of lipopolysaccharide-induced apoptosis by cilostazol in human umbilical vein endothelial cells
    Ki Young Kim
    Department of Pharmacology, College of Medicine, and Research Institute of Genetic Engineering, Pusan National University, Pusan, Korea
    J Pharmacol Exp Ther 300:709-15. 2002
    ....
  83. ncbi PDE5A inhibition attenuates bleomycin-induced pulmonary fibrosis and pulmonary hypertension through inhibition of ROS generation and RhoA/Rho kinase activation
    Anna R Hemnes
    Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, 720 Rutland Ave, Ross 850, Baltimore, MD 21205, USA
    Am J Physiol Lung Cell Mol Physiol 294:L24-33. 2008
    ....
  84. ncbi Cyclic AMP-dependent Cl secretion is regulated by multiple phosphodiesterase subtypes in human colonic epithelial cells
    S M O'Grady
    Department of Physiology, University of Minnesota, St Paul 55108, USA
    J Membr Biol 185:137-44. 2002
    ..These results indicate that inhibition of PDE activity in T84 cells stimulates transepithelial Cl secretion and that PDE1 and PDE3 are involved in regulating the rate of secretion...
  85. ncbi Sildenafil improves exercise capacity and quality of life in patients with systolic heart failure and secondary pulmonary hypertension
    Gregory D Lewis
    Cardiology Division, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
    Circulation 116:1555-62. 2007
    ..We tested the hypothesis that sildenafil, an effective therapy for pulmonary arterial hypertension, would lower pulmonary vascular resistance and improve exercise capacity in patients with HF complicated by PH...
  86. pmc Apremilast, a cAMP phosphodiesterase-4 inhibitor, demonstrates anti-inflammatory activity in vitro and in a model of psoriasis
    P H Schafer
    Department of Drug Discovery, Celgene Corporation, Summit, NJ 07901, USA
    Br J Pharmacol 159:842-55. 2010
    ....
  87. pmc Cyclic GMP regulation of the L-type Ca(2+) channel current in human atrial myocytes
    G Vandecasteele
    , INSERM U-446, , , , France
    J Physiol 533:329-40. 2001
    ..The effect of cGMP involves modulation of the cAMP level and PKA activity via opposite actions of the nucleotide on PDE2 and PDE3...
  88. ncbi Antiproliferative effects of phosphodiesterase type 5 inhibition in human pulmonary artery cells
    John Wharton
    Section on Experimental Medicine and Toxicology, Imperial College London, Hammersmith Campus, Du Cane Road, London W12 ONN, UK
    Am J Respir Crit Care Med 172:105-13. 2005
    ..Phosphodiesterase Type 5 (PDE5) inhibition represents a novel strategy for the treatment of pulmonary hypertension...
  89. pmc Protein kinase G-dependent cardioprotective mechanism of phosphodiesterase-5 inhibition involves phosphorylation of ERK and GSK3beta
    Anindita Das
    Division of Cardiology, Department of Internal Medicine, Virginia Commonwealth University, Richmond, Virginia 23298, USA
    J Biol Chem 283:29572-85. 2008
    ..Moreover, our results demonstrate that sildenafil activates a PKG-dependent novel signaling cascade that involves activation of ERK and inhibition of glycogen synthase kinase 3beta leading to cytoprotection...
  90. ncbi Erectile dysfunction following prostatectomy: prevention and treatment
    Ahmed Magheli
    Department of Urology, Charite University Medicine Berlin, Berlin, Germany
    Nat Rev Urol 6:415-27. 2009
    ..Continued prospective, rigorous study is needed to develop and bring forward this important field and to establish the best evidence basis for counseling and treating patients suffering from ED after RP...
  91. ncbi Nitric oxide and penile erectile function
    Noboru Toda
    Department of Pharmacology, Shiga University of Medical Science, Otsu, Japan
    Pharmacol Ther 106:233-66. 2005
    ..This article includes recent advances in research on physiological roles and pathophysiological implications of NO in penile erection and on novel therapy for ED in reference to NO...
  92. ncbi Retinal effects of 6 months of daily use of tadalafil or sildenafil
    William H Cordell
    Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana, USA
    Arch Ophthalmol 127:367-73. 2009
    ..To assess changes in electroretinography (ERG) and other retinal function parameters during 6 months of daily use of tadalafil, sildenafil citrate, or placebo...
  93. pmc Rolipram: a specific phosphodiesterase 4 inhibitor with potential antipsychotic activity
    S J Kanes
    Department of Psychiatry and Center for Neurobiology and Behavior, University of Pennsylvania, Philadelphia, PA 19104, USA
    Neuroscience 144:239-46. 2007
    ..Given previous reports showing rolipram improves cognition, we conclude that PDE4 represents an important novel target for further antipsychotic drug development...
  94. ncbi Sildenafil: from angina to erectile dysfunction to pulmonary hypertension and beyond
    Hossein A Ghofrani
    Medical Clinic II V, Department of Internal Medicine, University Hospital Giessen and Marburg, GmbH, Klinikstrasse 36, 35392 Giessen, Germany
    Nat Rev Drug Discov 5:689-702. 2006
    ....
  95. ncbi Molecular docking of competitive phosphodiesterase inhibitors
    Orly Dym
    University of California Los Angeles Department of Energy Laboratory of Structural Biology and Molecular Medicine, University of California Los Angeles, Los Angeles, California, USA
    Mol Pharmacol 61:20-5. 2002
    ..The binding of other PDE4 inhibitors (high- and low-affinity) was also modeled and used to predict the involvement of residues that were not previously implicated in pharmacological interactions...
  96. ncbi Phosphorylation and activation of hormone-sensitive adipocyte phosphodiesterase type 3B
    E Degerman
    Section for Molecular Signalling, Lund University, Lund, Sweden
    Methods 14:43-53. 1998
    ..In the review we describe methods and strategies used in the authors' laboratories to study phosphorylation and activation of PDE3B in adipocytes and in vitro...
  97. ncbi Effects of pentoxifylline on the different steps during adhesion and transendothelial migration of flowing neutrophils
    P S Bahra
    Department of Physiology, The Medical School, The University of Birmingham, Birmingham B15 2TT, UK
    Cell Biochem Funct 19:249-57. 2001
    ..Thus, by using a flow-based model, we have been able to separate the effects of a multipotent agent such as pentoxifylline, which acts on leucocytes and endothelial cells, at each stage of migration...
  98. ncbi Role of phosphodiesterase type 3A in rat oocyte maturation
    F J Richard
    Division of Reproductive Biology, Department of Gynecology and Obstetrics, Stanford University School of Medicine, Stanford, California 94305 5317, USA
    Biol Reprod 65:1444-51. 2001
    ..These findings strongly support the hypothesis that an increase in oocyte PDE3A activity is one of the intraoocyte mechanisms controlling resumption of meiosis in rat oocytes, at least in vitro...
  99. pmc Tyrosyl-DNA phosphodiesterase as a target for anticancer therapy
    Thomas S Dexheimer
    Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 37 Convent Drive, Bethesda, MD 20892 4255, USA
    Anticancer Agents Med Chem 8:381-9. 2008
    ..This review provides a summary of the biochemical and cellular processes performed by Tdp1 as well as the rationale behind the development of Tdp1 inhibitors for anticancer therapy...
  100. ncbi Phosphodiesterase type 5 is highly expressed in the hypertrophied human right ventricle, and acute inhibition of phosphodiesterase type 5 improves contractility
    Jayan Nagendran
    Pulmonary Hypertension Program, Department of Medicine, University of Alberta, Edmonton, Canada T6G 2B7
    Circulation 116:238-48. 2007
    ....
  101. ncbi Effect of inhaled iloprost plus oral sildenafil in patients with primary pulmonary hypertension
    H Wilkens
    Medizinische Klinik und Poliklinik, Innere Medizin V, Innere Medizin III, Homburg Saar, Germany
    Circulation 104:1218-22. 2001
    ..However, repetitive inhalations are required due to its short-term effects. One potential approach to prolong and increase the vasorelaxant effects of aerosolized iloprost might be to combine use with phosphodiesterase inhibitors.

Research Grants62

  1. Use of Phosphodiesterase Inhibitors to Evaluate the Pathobiology of CF
    JENNIFER L TAYLOR-COUSAR; Fiscal Year: 2013
    ..develops during the period of this award, to design a large, multi-center trial to determine if systemic PDEi administration will improve lung function, frequency of exacerbations and exercise tolerance in CF lung disease ..
  2. Cyclic AMP, Cytokine Modulation and Alcoholic Liver Disease
    Craig J McClain; Fiscal Year: 2013
    ..AH) and alcoholic cirrhosis, and evaluate whether in vitro incubation of monocytes with specific phosphodiesterase inhibitors corrects dysregulated cAMP and cytokine metabolism;2...
  3. Zipcode based nano-imaging of hypertensive pulmonary arteries
    Rubin M Tuder; Fiscal Year: 2010
    ..The current therapies, including prostacyclin and phosphodiesterase inhibitors extend survival, yet do not lead to regression or cure of the disease...
  4. TNF and Mitochondrial Dysfunction in ALD
    Craig J McClain; Fiscal Year: 2010
    ..The specific objectives of this proposal are: 1. Evaluate the role of cAMP and phosphodiesterase inhibitors on LPS-stimulated TNFproduction in ALD;2: Evaluate monocyte/Kupffer cell Toll-like receptor signaling ..
  5. Validation and development of trypanosomal phosphodiesterase inhibitors for treat
    Michael P Pollastri; Fiscal Year: 2013
    ....
  6. Regulation of CXCR4 by cognate and non-cognate ligands
    Elias Lolis; Fiscal Year: 2013
    ..We have identified five phosphodiesterase inhibitors, (including rolipram) that inhibit MIF...
  7. FUNCTIONAL PLASTICITY IN THE MAMMALIAN SPINAL CORD
    Harry G Goshgarian; Fiscal Year: 2013
    ..provided by applicant): In recent years, we have discovered that certain drugs (methylxanthines, phosphodiesterase inhibitors and selective A1 adenosine receptor antagonists) will induce plasticity in the respiratory pathways ..
  8. Drug Discovery Consortium for Chagas Disease
    Rick L Tarleton; Fiscal Year: 2010
    ..Specifically, the development of novel nitrotriazoles, isoprenoid pathway inhibitors, phosphodiesterase inhibitors, protease inhibitors and inhibitors of galactofuranose will be pursued by the academic and industrial ..
  9. Hormonal Regulation of Phosphodiestrases
    Marco Conti; Fiscal Year: 2012
    ..In view of the large number of programs in the pharmaceutical industry developing phosphodiesterase inhibitors for a variety of indications, a better understanding of the role of these targets in signaling will ..
  10. PRESERVATION AND CARDIAC TRANSPLANT VASCULOPATHY
    David Pinsky; Fiscal Year: 2003
    ..deficient second messenger pathways (NO,cAMP, cGMP) with substrates, analogs, or type specific phosphodiesterase inhibitors improves acute graft vascular function and causes a striking reduction in TCAD; these benefits were ..
  11. TARGETING CGMP KINASES TO DEVELOP NEW THERAPEUTICS FOR HYPERTENSIVE DISEASES
    CHOEL WOONG KIM; Fiscal Year: 2013
    ..drugs such as nitric oxide releasing agents for the treatment of many hypertensive diseases and phosphodiesterase inhibitors for the treatment of erectile dysfunction...
  12. ACTIVATION OF CFTR MUTANTS IN VIVO FOR CF THERAPY
    MITCHELL DRUMM; Fiscal Year: 1999
    ..inferior nasal turbinate of CF patients will be exposed to beta-adrenergic agonists and class-specific phosphodiesterase inhibitors, the combination of which has been found to induce CFTR-mediated chloride efflux from primary CF nasal ..
  13. CONTROL OF BLOOD ACTIVATION DURING OPEN HEART SURGERY
    L Edmunds; Fiscal Year: 2002
    ..Suppression of neutrophil and monocyte activation focuses on cyclic AMP, cyclic GMP and specific phosphodiesterase inhibitors (PDEs)...
  14. FETAL LUNG MATURATION: PREVENTION OF RDS
    John Johnston; Fiscal Year: 1992
    ..The effects of alpha and beta agonists, cyclic AMP analogs, and phosphodiesterase inhibitors on the levels of SP-35 and its mRNA will be defined...
  15. Bioactive Compounds from Acylnitroso Cycloadducts
    Marvin Miller; Fiscal Year: 2006
    ..nor analogs, carbocyclic forms of polyoxins, sinefungin, nucleoside Q, puromycin and analogs), novel phosphodiesterase inhibitors, streptazolin, novel oxazolidinone antibiotics, diketopiperazines (tryprostatin analogs), novel amino ..
  16. cGMP Phosphodiesterase Inhibitors in a Mouse Model of Duchenne Muscular Dystrophy
    STANLEY FROEHNER; Fiscal Year: 2009
    ..The research proposed here will test FDA-approved drugs (phosphodiesterase inhibitors) for their ability to slow the progression of muscle degeneration in muscular dystrophy...
  17. SPECIALIZED TRANSPORT PROPERTIES OF ALVEOLAR EPITHELIUM
    Barbara Goodman; Fiscal Year: 1992
    ..e., sodium transport inhibitors, beta-adrenergic agonists, cyclic AMP analogs, phosphodiesterase inhibitors, hydrocortisone, etc.)...
  18. MECHANISMS OF CL TRANSPORT IN EPITHELIAL CELLS
    Thomas Biber; Fiscal Year: 1992
    ..insulin), (2) cAMP and agents that stimulate its production (forskolin) and inhibit its breakdown (phosphodiesterase inhibitors), and (3) of changes in Ca2+...
  19. BEHAVIORAL AND RESPIRATORY EFFECTS OF METHYLXANTHINES
    Leonard Howell; Fiscal Year: 1993
    ..affinities for adenosine-receptor subtypes and in their potencies as adenosine antagonists or as phosphodiesterase inhibitors will be administered alone and in combination with adenosine agonists...
  20. MECHANISMS OF ANGIOTENSIN II: CYCLIC NUCLEOTIDES & CA2+
    LARRY BARNES; Fiscal Year: 1980
    ..are related to the action of A II, alteration of glomerular contractility to A II in the presence of phosphodiesterase inhibitors will be examined. In addition, the ability of cyclic nucleotides and their analogues, e.g...
  21. Phosphodiesterase-inhibitors, vascular integrity and SCI
    Raymond J Grill; Fiscal Year: 2010
    ..We propose to explore the nature of this chronic BSCB dysfunction over a time course of 1 year. In addition, we will also explore whether treatment with PDE-ls in the acute phase results in a repaired BSCB in the chronic. ..
  22. ADENOSINE ANALOGS AS CANCER CHEMOTHERAPEUTIC AGENTS
    Robert Parks; Fiscal Year: 1992
    ..effects of nucleoside transport and ADA in- hibitors, A A2 receptor agonists and antagonists and cAMP phosphodiesterase inhibitors will be examined with human blood platelets and proliferating and differentiated HL-60 promyelocytic ..
  23. SIGNAL TRANSDUCTION IN GASTROINTESTINAL NEURONS
    JACKIE WOOD; Fiscal Year: 1990
    ..of cAMP by intraneuronal injection, application of permeable analogs of cAMP or treatment with phosphodiesterase inhibitors also mimic slow EPSPs...
  24. ROLE OF C-AMP IN RENIN RELEASE
    WINFRED MAGEE; Fiscal Year: 1990
    ..prostaglandin I2, isoproterenol, 9-substituted adenosine derivatives, phosphodiesterase inhibitors, protein kinase inhibitors) will be used to test our hypothesis...
  25. MESOIONIC PURINONES AS PHOSPHODIESTERASE INHIBITORS
    RICHARD GLENNON; Fiscal Year: 1980
    ..Because of the potential therapeutic application of phosphodiesterase inhibitors, especially in the treatment of cardiovascular diseases, we propose to further investigate this new ..
  26. Mesenchymal Stem Cells for Myocardial Infarction
    Robert Kloner; Fiscal Year: 2006
    ..abstract_text> ..
  27. Biologic Ventricular Assist Device
    Robert Kloner; Fiscal Year: 2004
    ..Identification and characterization of transplants will be carried out with PCR analysis of the Y chromosome (male cells into female host), detailed histologic analysis and immunostaining for muscle cell markers. ..
  28. COLLABORATIVE R01-CARDIAC GRAFTS-FUNCTIONAL ANALYSES
    Robert Kloner; Fiscal Year: 2003
    ....
  29. MOLECULAR REGULATION OF ADENOSINE INHIBITION IN LDT/PPT
    Paul Rosenberg; Fiscal Year: 2000
    ..techniques to characterize the phosphodiesterases present in the LDT; (2) Characterize the effect of phosphodiesterase inhibitors on adenosine accumulation and cyclic nucleotide metabolism in the LDT; (3) Characterize the effect of ..
  30. 2008 AUA/SBUR Summer Research Conference
    Arthur Burnett; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable]..
  31. NITRIC OXIDE REGULATORY SYSTEM IN THE PENIS
    Arthur Burnett; Fiscal Year: 2002
    ....
  32. REGULATION OF PROSTATE GROWTH BY NEURAL FACTORS
    Kevin McVary; Fiscal Year: 2001
    ..Using this model allows one to explore the limits of understanding prostatic neuroregulation, to explore neurotrophic influences on exocrine gland development, and to possibly uncover novel methods to influence prostate disease. ..
  33. Molecular Control of cGMP Signaling by PKGs and PDEs
    Jackie Corbin; Fiscal Year: 2007
    ..A thorough physical and biochemical characterization of PDE11 will be carded out, and the likelihood of regulation of this enzyme by ligand binding to its GAF domains or by enzyme phosphorylation will be explored. ..
  34. The Efficacy of TUMT and Neoadjuvant Finasteride for BPH
    Kevin McVary; Fiscal Year: 2005
    ..We are proposing a 3-arm, placebo/sham controlled, randomized clinical trial using changes in symptoms as the primary ..
  35. Molecular Mechanisms of PDE5 Regulation
    Jackie Corbin; Fiscal Year: 2005
    ..Results of these studies will provide a basis for understanding fundamental questions relating to cGMP signaling in many tissues. ..
  36. N O S AND NEUROPATHIC AND ENDOTHELIAL INDUCED ED
    Kevin McVary; Fiscal Year: 2002
    ..Results of this research will aid in the understanding of how diabetic neuropathy contributes to sexual dysfunction and elucidate possible mechanisms to prevent them. ..
  37. Amine N-Oxygenation by FMO3 and FMO4
    John Cashman; Fiscal Year: 2005
    ..Such fundamental information will be useful in the development of safer drugs, the prevention of adverse drug reactions and the protection of humans from disease. ..
  38. Central betal adrenergic receptors and behavior
    Han Ting Zhang; Fiscal Year: 2004
    ..This will lead to the better understanding of pathophysiology and pharmacotherapy of depression. ..
  39. PDE-5 Inhibition in HIV+ and HIV- Men
    Raymond Rosen; Fiscal Year: 2005
    ..Key personnel for the project are Raymond C. Rosen, Ph.D., Professor of Psychiatry and Medicine at UMDNJ, who will serve as PI, and Joseph Catania, PhD, co-PI, from the AIDS Research Institute at UCSF. ..
  40. Sexual Dysfunction and Diabetes:Look AHEAD Sub-Study
    Stephen Schneider; Fiscal Year: 2006
    ..iii) Finally, the proposed sub-study will investigate the relationship between changes in sexual function and quality of life outcomes. ..
  41. COMBINATORIAL PHARMACOTHERAPIES FOR COCAINE DEPENDENCE
    John Cashman; Fiscal Year: 2001
    ..The study will provide an understanding of the structural and pharmaceutical properties of hDAT antagonists. The work will lead to new insight into the preparation of human medications necessary in the cessation of cocaine abuse. ..
  42. New Opioids for Alcoholism
    John Cashman; Fiscal Year: 2006
    ..The potential commercial application of the work is that the research could lead to a 'blockbuster' drug product. [unreadable] [unreadable]..
  43. EXCITATORY AMINO ACIDS IN GLAUCOMA
    Alan Laties; Fiscal Year: 2004
    ..These experiments will help test the central hypothesis--for if one can block the effects of IOP elevation with glutamate antagonists, then elevated 10P may toxic glutamate levels ganglion cell loss. ..
  44. SIGNALING MECHANISMS IN PHARMACOLOGICAL PRECONDITIONING
    RAKESH KUKREJA; Fiscal Year: 2004
    ..These studies will help us learn a great deal on the endogenous mechanisms of delayed preconditioning and assist us in developing innovative techniques leading to one of the most effective means of salvaging ischemic myocardium. ..
  45. NEUROPSYCHIATRIC EFFECTS OF TESTOSTERONE IN MEN
    Stuart Seidman; Fiscal Year: 2004
    ..abstract_text> ..
  46. cAMP Phosphodiesterase and Lung Endothelial Cell Permeability
    Thomas C Rich; Fiscal Year: 2010
    ..Here we propose to determine whether pharmacological and molecular inhibitors of a specific protein, phosphodiesterase type 7, prevent increases in endothelial permeability in these arteries, and hence, make breathing easier. ..
  47. FEMALE SEXUAL AROUSAL: CLITORAL AND VAGINAL PHYSIOLOGY
    Abdulmaged Traish; Fiscal Year: 2003
    ....
  48. New Strategies to Enhance Drug Adherence in Hypertension
    Robert DeBusk; Fiscal Year: 2003
    ..Demonstration of the efficacy of nurse case management of hypertension in the proposed project may facilitate the dissemination of this approach to underserved populations throughout the U.S. ..
  49. CYCLIC AMP/ADENOSINE PATHWAY
    Edwin Jackson; Fiscal Year: 2002
    ..abstract_text> ..
  50. LEPTIN ACTION ON HYPOTHALAMIC PEPTIDES GOVERNING FEEDING
    Abhiram Sahu; Fiscal Year: 2001
    ..These studies will further our understanding of leptin signaling in the hypothalamus in relation to feeding, and therefore will be relevant to the development of therapeutic approaches to eating disorders. ..
  51. CELL-SELECTIVE EXPRESSION OF FIBROTIC GENE PATHWAYS
    Nestor Gonzalez Cadavid; Fiscal Year: 2008
    ..We expect that our studies would lead to the detection of novel targets of antifibrotic therapy for penile and vascular diseases of considerable public health impact. [unreadable] [unreadable] [unreadable]..
  52. MOLECULAR MECHANISMS OF DELAYED PRECONDITIONING
    RAKESH KUKREJA; Fiscal Year: 2006
    ..The information obtained from these studies may help us design novel therapies for protection of the heart against I/R injury. ..
  53. Cyclic AMP signaling in cardiac myocytes
    THOMAS RICH; Fiscal Year: 2007
    ..g., protenoid, beta1-,or beta2-adrenergic receptors) or inhibit phosphodiesterase (PDE) will shed new light on the physiologic functions of these enzymes and their relation to cardiac function. ..
  54. ERECTILE DYSFUNCTION AND NITRIC OXIDE SYNTHASE IN AGING
    Nestor Gonzalez Cadavid; Fiscal Year: 2006
    ....
  55. INFLAMMATION & CORTICOSTEROID RESPONSES IN SEVERE ASTHMA
    KIAN CHUNG; Fiscal Year: 2005
    ..The molecular mechanisms underlying loss of CR will be examined. These studies should lead to more effective therapies for chronic severe asthma. ..
  56. Urodynamic and Multiethnic Variability of Men Treated b*
    Steven Kaplan; Fiscal Year: 2005
    ..Baseline urodynamic parameters which may predict improved outcome after MIST 3. The success of various types of MIST in treating BPH in African - American, Hispanic and Caucasian men. ..
  57. Mechanisms of Leptin Signaling in the Hypothalamus
    Abhiram Sahu; Fiscal Year: 2007
    ..These studies will further our understanding of leptin signaling in the hypothalamus in relation to feeding, and therefore will be relevant to the development of therapeutic approaches to eating disorders. [unreadable] [unreadable]..
  58. AGE RELATED CARDIAC SENSITIVITY TO VOLATILE ANESTHETICS
    Y S Prakash; Fiscal Year: 2001
    ....
  59. MECHANISMS OF RENAL TUBULAR EPITHELIAL CELL INJURY
    Sudhir Shah; Fiscal Year: 2005
    ..abstract_text> ..
  60. CHRONIC ISCHEMIC LEFT VENTRICULAR DYSFUNCTION
    Sanjiv Kaul; Fiscal Year: 2004
    ..The drug we will test is carvedilol because of its unique adrenergic inhibitor properties as well as its anti-oxidant and anti-apoptotic properties. ..
  61. Alcohol, iNOS upregulation, leaky gut & liver disease
    Ali Keshavarzian; Fiscal Year: 2009
    ..Significance: Showing that ALD requires a leaky gut, &that NO &cytoskeletal pathways are involved, could 1) identify drinkers at risk for LD (sugar test);2) lead to therapies to prevent LD in those drinkers unable to abstain. ..
  62. Folate in Schizophrenia
    Donald C Goff; Fiscal Year: 2010
    ..This will be the first adequately-powered study to assess efficacy and identify predictors of response. ..