aminopyridines

Summary

Summary: Pyridines substituted in any position with an amino group. May be hydrogenated, but must retain at least one double bond.

Top Publications

  1. ncbi Roflumilast in symptomatic chronic obstructive pulmonary disease: two randomised clinical trials
    Peter M A Calverley
    School of Clinical Sciences, Liverpool, UK
    Lancet 374:685-94. 2009
  2. ncbi Roflumilast in moderate-to-severe chronic obstructive pulmonary disease treated with longacting bronchodilators: two randomised clinical trials
    Leonardo M Fabbri
    University of Modena and Reggio Emilia, Modena, Italy
    Lancet 374:695-703. 2009
  3. pmc N-myristoyltransferase inhibitors as new leads to treat sleeping sickness
    Julie A Frearson
    Drug Discovery Unit, Division of Biological Chemistry and Drug Discovery, University of Dundee, Dundee DD1 5EH, UK
    Nature 464:728-32. 2010
  4. 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
  5. 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
  6. ncbi Roflumilast with long-acting β2-agonists for COPD: influence of exacerbation history
    E D Bateman
    University of Cape Town Lung Institute, Cape Town, South Africa
    Eur Respir J 38:553-60. 2011
  7. pmc Reduction of exacerbations by the PDE4 inhibitor roflumilast--the importance of defining different subsets of patients with COPD
    Stephen I Rennard
    Nebraska Medical Center, Omaha, Nebraska, USA
    Respir Res 12:18. 2011
  8. pmc Cost-effectiveness of available treatment options for patients suffering from severe COPD in the UK: a fully incremental analysis
    Nadine Hertel
    IMS Consulting Group, London, UK
    Int J Chron Obstruct Pulmon Dis 7:183-99. 2012
  9. pmc Correctors of ΔF508 CFTR restore global conformational maturation without thermally stabilizing the mutant protein
    Lihua He
    Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, NC 27599 7248, USA
    FASEB J 27:536-45. 2013
  10. ncbi 3,5-Diaryl-2-aminopyridines as a novel class of orally active antimalarials demonstrating single dose cure in mice and clinical candidate potential
    Yassir Younis
    Department of Chemistry, University of Cape Town, Rondebosch 7701, South Africa
    J Med Chem 55:3479-87. 2012

Detail Information

Publications244 found, 100 shown here

  1. ncbi Roflumilast in symptomatic chronic obstructive pulmonary disease: two randomised clinical trials
    Peter M A Calverley
    School of Clinical Sciences, Liverpool, UK
    Lancet 374:685-94. 2009
    ..We therefore investigated whether roflumilast would reduce the frequency of exacerbations requiring corticosteroids in patients with COPD...
  2. ncbi Roflumilast in moderate-to-severe chronic obstructive pulmonary disease treated with longacting bronchodilators: two randomised clinical trials
    Leonardo M Fabbri
    University of Modena and Reggio Emilia, Modena, Italy
    Lancet 374:695-703. 2009
    ..The effect of roflumilast on lung function in patients with COPD that is moderate to severe who are already being treated with salmeterol or tiotropium was investigated...
  3. pmc N-myristoyltransferase inhibitors as new leads to treat sleeping sickness
    Julie A Frearson
    Drug Discovery Unit, Division of Biological Chemistry and Drug Discovery, University of Dundee, Dundee DD1 5EH, UK
    Nature 464:728-32. 2010
    ..Our studies validate T. brucei N-myristoyltransferase as a promising therapeutic target for human African trypanosomiasis...
  4. 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...
  5. 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...
  6. ncbi Roflumilast with long-acting β2-agonists for COPD: influence of exacerbation history
    E D Bateman
    University of Cape Town Lung Institute, Cape Town, South Africa
    Eur Respir J 38:553-60. 2011
    ..No differences arose in adverse events between these subgroups. Roflumilast may be used to reduce exacerbations and improve dyspnoea and lung function, without increasing adverse events in COPD patients receiving concomitant LABAs...
  7. pmc Reduction of exacerbations by the PDE4 inhibitor roflumilast--the importance of defining different subsets of patients with COPD
    Stephen I Rennard
    Nebraska Medical Center, Omaha, Nebraska, USA
    Respir Res 12:18. 2011
    ..This led to the question of whether a responsive subset existed that could be investigated further...
  8. pmc Cost-effectiveness of available treatment options for patients suffering from severe COPD in the UK: a fully incremental analysis
    Nadine Hertel
    IMS Consulting Group, London, UK
    Int J Chron Obstruct Pulmon Dis 7:183-99. 2012
    ..This study aimed to assess the lifetime costs and outcomes associated with alternative treatment regimens for patients with severe COPD in the UK setting...
  9. pmc Correctors of ΔF508 CFTR restore global conformational maturation without thermally stabilizing the mutant protein
    Lihua He
    Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, NC 27599 7248, USA
    FASEB J 27:536-45. 2013
    ..He, L., Kota, P., Aleksandrov, A. A., Cui, L., Jensen, T., Dokholyan, N. V., Riordan, J. R. Correctors of ΔF508 CFTR restore global conformational maturation without thermally stabilizing the mutant protein...
  10. ncbi 3,5-Diaryl-2-aminopyridines as a novel class of orally active antimalarials demonstrating single dose cure in mice and clinical candidate potential
    Yassir Younis
    Department of Chemistry, University of Cape Town, Rondebosch 7701, South Africa
    J Med Chem 55:3479-87. 2012
    A novel class of orally active antimalarial 3,5-diaryl-2-aminopyridines has been identified from phenotypic whole cell high-throughput screening of a commercially available SoftFocus kinase library...
  11. pmc Roflumilast inhibits the release of chemokines and TNF-α from human lung macrophages stimulated with lipopolysaccharide
    A Buenestado
    Laboratory of Pulmonary Pharmacology UPRES EA220, Foch Hospital, University Versailles Saint Quentin, Suresnes, France
    Br J Pharmacol 165:1877-90. 2012
    ....
  12. pmc Roflumilast N-oxide, a PDE4 inhibitor, improves cilia motility and ciliated human bronchial epithelial cells compromised by cigarette smoke in vitro
    J Milara
    Research Unit, University General Hospital Consortium, Valencia, Spain
    Br J Pharmacol 166:2243-62. 2012
    ....
  13. pmc Kv7 potassium channels in airway smooth muscle cells: signal transduction intermediates and pharmacological targets for bronchodilator therapy
    Lioubov I Brueggemann
    Department of Molecular Pharmacology and Therapeutics, Loyola University Chicago, Maywood, IL 60153, USA
    Am J Physiol Lung Cell Mol Physiol 302:L120-32. 2012
    ....
  14. pmc Transcriptional repression of the M channel subunit Kv7.2 in chronic nerve injury
    Kirstin Rose
    Institute of Membrane and Systems Biology, Faculty of Biological Science, University of Leeds, Leeds, UK
    Pain 152:742-54. 2011
    ..Our work suggests a novel mechanism for neuropathic overexcitability and brings focus on M channels and REST as peripheral targets for the treatment of neuropathic pain...
  15. ncbi Molecular pharmacology and therapeutic potential of neuronal Kv7-modulating drugs
    Francesco Miceli
    Section of Pharmacology, Department of Neuroscience, University of Naples Federico II, Naples, Italy
    Curr Opin Pharmacol 8:65-74. 2008
    ....
  16. ncbi Treatment of chronic obstructive pulmonary disease with roflumilast, a new phosphodiesterase 4 inhibitor
    Nicholas J Gross
    Department of Medicine, St Francis Hospital and Medical Center, Hartford, Connecticut 06105 1208, USA
    COPD 7:141-53. 2010
    ....
  17. ncbi Regulation of adipocyte differentiation by activation of serotonin (5-HT) receptors 5-HT2AR and 5-HT2CR and involvement of microRNA-448-mediated repression of KLF5
    Minako Kinoshita
    Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Sakyo ku, Kyoto, Japan
    Mol Endocrinol 24:1978-87. 2010
    ..In this study, we identified the regulation of adipocyte differentiation by 5-HT, 5-HT(2A)R, and 5-HT(2C)R. miR-448-mediated repression of KLF5 was identified as a negative regulator for adipocyte differentiation...
  18. pmc The reno-vascular A2B adenosine receptor protects the kidney from ischemia
    Almut Grenz
    Department of Pharmacology and Toxicology, Tubingen University Hospital, Tubingen, Germany Mucosal Inflammation Program, Department of Anesthesiology and Perioperative Medicine, University of Colorado Health Sciences Center, Denver, Colorado, USA
    PLoS Med 5:e137. 2008
    ..Here, we identified a novel pathway of renal protection from ischemia using ischemic preconditioning (IP)...
  19. pmc Reduction in sputum neutrophil and eosinophil numbers by the PDE4 inhibitor roflumilast in patients with COPD
    Diana C Grootendorst
    Department of Pulmonology, Leiden University Medical Center, Leiden, The Netherlands
    Thorax 62:1081-7. 2007
    ..Results from in vitro studies with roflumilast indicate that it has anti-inflammatory properties that may be applicable for the treatment of COPD...
  20. ncbi Inhibition of inflammation and remodeling by roflumilast and dexamethasone in murine chronic asthma
    Rakesh K Kumar
    Department of Pathology, University of New South Wales, Sydney, Australia
    J Pharmacol Exp Ther 307:349-55. 2003
    ..Roflumilast did not diminish accumulation of transforming growth factor-beta1, suggesting that it might affect remodeling by mechanisms distinct from glucocorticoids...
  21. pmc Roflumilast attenuates allergen-induced inflammation in mild asthmatic subjects
    Gail M Gauvreau
    Department of Medicine, McMaster University, Hamilton, Ontario, Canada
    Respir Res 12:140. 2011
    ..The objective of this study was to evaluate the effects of roflumilast on bronchoconstriction, airway hyperresponsiveness (AHR), and airway inflammation in mild asthmatic patients undergoing allergen inhalation challenge...
  22. pmc Bimodal effects of the Kv7 channel activator retigabine on vascular K+ currents
    Sym Yeung
    Division of Basic Medical Sciences, Ion Channels and Cell Signalling Research Centre, St George s University of London, London, UK
    Br J Pharmacol 155:62-72. 2008
    ..This study investigated the functional and electrophysiological effects of the Kv7 channel activator, retigabine, on murine portal vein smooth muscle...
  23. pmc Functional magnetic resonance imaging reveals different neural substrates for the effects of orexin-1 and orexin-2 receptor antagonists
    Alessandro Gozzi
    Center for Nanotechnology Innovation, Istituto Italiano di Tecnologia, Pisa, Italy
    PLoS ONE 6:e16406. 2011
    ..The subcortical and striatal pattern observed with GSK1059865 represent a possible neurofunctional correlate for the modulatory role of OX1R in controlling reward-processing and goal-oriented behaviours in the rat...
  24. ncbi Cardioprotection by ecto-5'-nucleotidase (CD73) and A2B adenosine receptors
    Tobias Eckle
    Department of Anesthesiology and Intensive Care Medicine, Tubingen University Hospital, Hoppe Seyler Str 3, D 72076 Tubingen, Germany
    Circulation 115:1581-90. 2007
    ..Once generated, adenosine can activate cell-surface adenosine receptors (A1 AR, A2A AR, A2B AR, A3 AR). In the present study, we define the contribution of adenosine to cardioprotection by ischemic preconditioning...
  25. ncbi Aminopyridines correct early dysfunction and delay neurodegeneration in a mouse model of spinocerebellar ataxia type 1
    Raphael Hourez
    Laboratory of Neurophysiology, Universite Libre de Bruxelles, 1070 Brussels, Belgium
    J Neurosci 31:11795-807. 2011
    ..SCA1 mice are treated with aminopyridines, acting as potassium channel blockers to test whether the treatment could improve neuronal dysfunction, motor ..
  26. pmc In vitro and in vivo activities of 2-aminopyrazines and 2-aminopyridines in experimental models of human African trypanosomiasis
    Suman K Vodnala
    Department of Microbiology, Karolinska Institutet, Stockholm, Sweden
    Antimicrob Agents Chemother 57:1012-8. 2013
    ..New drugs for the treatment of human African trypanosomiasis are urgently needed. A number of 2-aminopyrazines/2-aminopyridines were identified as promising leads following a focused screen of 5,500 compounds for Trypanosoma brucei subsp...
  27. ncbi Discovery of N-(4-(2-amino-3-chloropyridin-4-yloxy)-3-fluorophenyl)-4-ethoxy-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide (BMS-777607), a selective and orally efficacious inhibitor of the Met kinase superfamily
    Gretchen M Schroeder
    Bristol Myers Squibb Research and Development, Princeton, New Jersey, 08543 4000, USA
    J Med Chem 52:1251-4. 2009
    ..Because of its excellent in vivo efficacy and favorable pharmacokinetic and preclinical safety profiles, 10 has been advanced into phase I clinical trials...
  28. pmc LPS-induced lung inflammation in marmoset monkeys - an acute model for anti-inflammatory drug testing
    Sophie Seehase
    Airway Research, Fraunhofer Institute for Toxicology and Experimental Medicine, Hannover, Germany
    PLoS ONE 7:e43709. 2012
    ....
  29. pmc Functional dissociation between PIKfyve-synthesized PtdIns5P and PtdIns(3,5)P2 by means of the PIKfyve inhibitor YM201636
    Diego Sbrissa
    Department of Physiology, Wayne State University School of Medicine, Detroit, Michigan, USA
    Am J Physiol Cell Physiol 303:C436-46. 2012
    ....
  30. pmc Roflumilast, a phosphodiesterase 4 inhibitor, alleviates bleomycin-induced lung injury
    J Cortijo
    Department of Pharmacology, University of Valencia, Spain
    Br J Pharmacol 156:534-44. 2009
    ..The effects of a phosphodiesterase 4 (PDE4) inhibitor, roflumilast, on bleomycin-induced lung injury were explored in 'preventive' and 'therapeutic' protocols and compared with glucocorticoids...
  31. ncbi Stimulation of serotonin2C receptors influences cocaine-seeking behavior in response to drug-associated stimuli in rats
    Silvia Burbassi
    Experimental Psychopharmacology, Department of Neuroscience, Istituto di Ricerche Farmacologiche Mario Negri, Via La Masa 19, 20156 Milan, Italy
    Psychopharmacology (Berl) 196:15-27. 2008
    ....
  32. 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...
  33. 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...
  34. ncbi Differential effects of the 5-HT(2A) receptor antagonist M100907 and the 5-HT(2C) receptor antagonist SB242084 on cocaine-induced locomotor activity, cocaine self-administration and cocaine-induced reinstatement of responding
    Paul J Fletcher
    Departments of Psychiatry and Psychology, University of Toronto, Toronto, Ontario, Canada
    Neuropsychopharmacology 27:576-86. 2002
    ..These results indicate distinct, and in some cases opposite, effects of a 5-HT(2A) compared with a 5-HT(2C) receptor antagonist on various cocaine-mediated behavioral effects...
  35. ncbi A phosphodiesterase 4 inhibitor, roflumilast N-oxide, inhibits human lung fibroblast functions in vitro
    F Sabatini
    Pulmonary Disease Unit, G Gaslini Institute, Largo G Gaslini 5, 16147 Genoa, Italy
    Pulm Pharmacol Ther 23:283-91. 2010
    ..Taken together, these findings indicate that roflumilast N-oxide directly targets human lung fibroblasts, which may at least partially explain the efficacy of roflumilast to mitigate a pulmonary fibrotic response in vivo...
  36. ncbi AZD2184: a radioligand for sensitive detection of beta-amyloid deposits
    Allan E Johnson
    Disease Biology, AstraZeneca R and D, Sodertalje, Sweden
    J Neurochem 108:1177-86. 2009
    ..Taken together, the pre-clinical profile of AZD2184 in relation to the reference ligand PIB, suggests that (11)C-labeled AZD2184 is a potential radioligand for PET-visualization of beta-amyloid deposits in the living human brain...
  37. ncbi Retigabine and flupirtine exert neuroprotective actions in organotypic hippocampal cultures
    Francesca Boscia
    Division of Pharmacology, Department of Neuroscience, School of Medicine, University of Naples Federico II, Naples, Italy
    Neuropharmacology 51:283-94. 2006
    ....
  38. ncbi BMS-777607, a small-molecule met kinase inhibitor, suppresses hepatocyte growth factor-stimulated prostate cancer metastatic phenotype in vitro
    Yao Dai
    Department of Radiation Oncology, University of Florida, Cancer Genetic Research Complex, Room 485E, Gainesville, Florida 32610, USA
    Mol Cancer Ther 9:1554-61. 2010
    ....
  39. ncbi Population pharmacokinetic modelling of roflumilast and roflumilast N-oxide by total phosphodiesterase-4 inhibitory activity and development of a population pharmacodynamic-adverse event model
    Gezim Lahu
    Department of Pharmacometrics and Pharmacokinetics, Nycomed GmbH, Byk Gulden Strasse 2, Konstanz, Germany
    Clin Pharmacokinet 49:589-606. 2010
    ..Both roflumilast and its metabolite roflumilast N-oxide have anti-inflammatory properties that contribute to overall pharmacological activity...
  40. pmc Effect of roflumilast on inflammatory cells in the lungs of cigarette smoke-exposed mice
    Piero A Martorana
    Department of Physiopathology and Experimental Medicine, University of Siena, Siena, Italy
    BMC Pulm Med 8:17. 2008
    ..Here we investigated the effects of roflumilast on the volume density (VV) of the inflammatory cells present in the lungs after chronic cigarette smoke exposure...
  41. pmc Concomitant facilitation of GABAA receptors and KV7 channels by the non-opioid analgesic flupirtine
    Felicia Klinger
    Center for Physiology and Pharmacology, Department of Neurophysiology and Neuropharmacology, Medical University of Vienna, Austria
    Br J Pharmacol 166:1631-42. 2012
    ..It is characterized as a selective neuronal potassium channel opener (SNEPCO). Nevertheless, its mechanisms of action remain controversial and are the purpose of this study...
  42. ncbi PDE4 inhibition: a novel approach for the treatment of inflammatory bowel disease
    Katharine H Banner
    Pfizer Global Research and Development, Discovery Biology, Allergy and Respiratory Group, Ramsgate Road, Sandwich, Kent CT13 9NJ, UK
    Trends Pharmacol Sci 25:430-6. 2004
    ..In this review, we summarize for the first time the evidence that PDE4 inhibitors might have therapeutic benefit in IBD, and discuss mechanisms of action beyond the inhibition of inflammatory cells...
  43. ncbi A direct intramolecular C-H amination reaction cocatalyzed by copper(II) and iron(III) as part of an efficient route for the synthesis of pyrido[1,2-a]benzimidazoles from N-aryl-2-aminopyridines
    Honggen Wang
    State Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, 190 Kaiyuan Avenue, Guangzhou 510530, China
    J Am Chem Soc 132:13217-9. 2010
    ..synthesis of pyrido[1,2-a]benzimidazoles through direct intramolecular aromatic C-H amination of N-aryl-2-aminopyridines has been developed...
  44. pmc A selective PIKfyve inhibitor blocks PtdIns(3,5)P(2) production and disrupts endomembrane transport and retroviral budding
    Harold B J Jefferies
    London Research Institute Cancer Research UK, Lincoln s Inn Fields Laboratories, 44 Lincoln s Inn Fields, London WC2A 3PX, UK
    EMBO Rep 9:164-70. 2008
    ..We concluded that the phosphatidylinositol 3,5-bisphosphate pathway is integral to endosome formation, determining morphology and cargo flux...
  45. ncbi Roflumilast inhibits lipopolysaccharide-induced inflammatory mediators via suppression of nuclear factor-kappaB, p38 mitogen-activated protein kinase, and c-Jun NH2-terminal kinase activation
    Hyun Jeong Kwak
    Laboratory of Molecular Pharmacology and Physiology, Medicinal Science Division, Korea Research Institute of Chemical Technology, P O Box 107, Yusung Gu, TaeJon 305 343, Korea
    J Pharmacol Exp Ther 315:1188-95. 2005
    ..These results suggest that the inhibitory activity of roflumilast on the production of inflammatory mediators seems to be mediated via inhibition of NF-kappaB, p38 MAP kinase, and JNK activation in macrophages...
  46. ncbi Novel pyrrolyl 2-aminopyridines as potent and selective human beta-secretase (BACE1) inhibitors
    Michael S Malamas
    Department of Chemical Sciences, Wyeth, CN 8000, Princeton, NJ 08543 8000, USA
    Bioorg Med Chem Lett 20:2068-73. 2010
    ..X-ray crystallographic studies indicated that the 2-aminopyridine moiety interacts directly with the catalytic aspartic acids Asp32 and Asp228 via a hydrogen-bonding network...
  47. ncbi CS055 (Chidamide/HBI-8000), a novel histone deacetylase inhibitor, induces G1 arrest, ROS-dependent apoptosis and differentiation in human leukaemia cells
    Ke Gong
    College of Life Sciences, Wuhan University, Wuhan 430072, PR China
    Biochem J 443:735-46. 2012
    ..In conclusion, our findings demonstrate that CS055 is a novel HDACi with potential chemotherapeutic value in several haematological malignancies, especially leukaemia...
  48. ncbi A novel histone deacetylase inhibitor Chidamide induces apoptosis of human colon cancer cells
    Lin Liu
    Department of Oncology, Zhong Da Hospital of Southeast University, Nanjing 210009, Jiangsu, PR China
    Biochem Biophys Res Commun 392:190-5. 2010
    ..Our data support the potential application of Chidamide as an anticancer agent in treating colon cancer. Future studies are needed to demonstrate its in vivo efficacy...
  49. ncbi Additive anti-inflammatory effects of beta 2 adrenoceptor agonists or glucocorticosteroid with roflumilast in human peripheral blood mononuclear cells
    Stacey L Tannheimer
    Respiratory Research, Gilead Sciences Inc, 199 East Blaine St, Seattle, WA 98102, USA
    Pulm Pharmacol Ther 25:178-84. 2012
    ..Addition of roflumilast to either a β2 adrenoceptor agonist or a glucocorticosteroid may provide superior anti-inflammatory activity and greater efficacy in COPD patients and be dose sparing...
  50. ncbi Aminopyridines for the treatment of cerebellar and ocular motor disorders
    Michael Strupp
    Department of Neurology, University of Munich, Klinikum Grosshadern, Munich, Germany
    Prog Brain Res 171:535-41. 2008
    ..Animal experiments have shown that aminopyridines [3,4-diaminopyridine (3,4-DAP) and 4-aminopyridine (4-AP)], nonselective blockers of the Kv family of voltage-..
  51. pmc Roflumilast-N-oxide induces surfactant protein expression in human alveolar epithelial cells type II
    Kerstin Höhne
    Division of Internal Medicine, Department of Pneumology, University Medical Centre, Freiburg, Germany
    PLoS ONE 7:e38369. 2012
    ..Roflumilast-N-oxide fosters the expression of SPs in human AEC-II via increase of intracellular cAMP levels potentially contributing to improved alveolar host defence and enhanced resolution of inflammation...
  52. ncbi Highly potent aminopyridines as Syk kinase inhibitors
    Marcos Castillo
    Almirall Barcelona Science Park Unit, Barcelona Science Park, 08028 Barcelona, Spain
    Bioorg Med Chem Lett 22:5419-23. 2012
    ..Substitution by a 2-pyrazinyl motif and SAR expansion in position 4 of the central core provided diverse potent non-cytotoxic Syk inhibitors showing nanomolar activity inhibiting human mast cell line LAD2 degranulation...
  53. ncbi M channels containing KCNQ2 subunits modulate norepinephrine, aspartate, and GABA release from hippocampal nerve terminals
    Maria Martire
    Institute of Pharmacology, School of Medicine, Catholic University of Sacred Heart, 00168 Rome, Italy
    J Neurosci 24:592-7. 2004
    ..These findings provide novel evidence for a major regulatory role of KCNQ2 K+ channel subunits in neurotransmitter release from rat hippocampal nerve endings...
  54. ncbi Photoinduced amino-imino tautomerism: an infrared study of 2-amino-5-methylpyridine in a low-temperature argon matrix
    Nobuyuki Akai
    Center for Quantum Life Sciences, Hiroshima University, 1 3 1, Kagamiyama, Higashi Hiroshima, Hiroshima 739 8530, Japan
    J Phys Chem A 110:6016-22. 2006
    ..The IR spectra of 2-amino-5-methylpyridine in the T(1) state and 5-methyl-2-pyridinamino radical were also obtained by UV irradiation (lambda>or= 300 nm)...
  55. ncbi The use of aminopyridines in neurological disorders
    Saam Sedehizadeh
    Department of Clinical Neurology, Queen s Medical Centre, Nottingham, UK
    Clin Neuropharmacol 35:191-200. 2012
    b>Aminopyridines are members of a family of monoamino and diamino derivatives of pyridine, and their principal mechanism of action is dose-dependent blockade of voltage-gated potassium channels, in particular, fast voltage-gated potassium ..
  56. ncbi Determination of arylamines and aminopyridines in pharmaceutical products using in-situ derivatization and liquid chromatography-mass spectrometry
    Gerd Vanhoenacker
    Research Institute for Chromatography, Kortrijk, Belgium
    J Chromatogr A 1216:3563-70. 2009
    Arylamines and aminopyridines form a class of potentially genotoxic impurities (PGIs) that can be present at trace levels in active pharmaceutical ingredients (APIs)...
  57. ncbi Impact of the small molecule Met inhibitor BMS-777607 on the metastatic process in a rodent tumor model with constitutive c-Met activation
    Yao Dai
    Department of Radiation Oncology, University of Florida, Gainesville, FL 32610, USA
    Clin Exp Metastasis 29:253-61. 2012
    ..Together, the present findings demonstrate that the disruption of c-Met signaling by BMS-777607 significantly impairs the metastatic phenotype, suggesting that this agent may have therapeutic utility in targeting cancer metastasis...
  58. pmc CCT244747 is a novel potent and selective CHK1 inhibitor with oral efficacy alone and in combination with genotoxic anticancer drugs
    Mike I Walton
    Cancer Research UK Cancer Therapeutics Unit, Division of Cancer Therapeutics, The Institute of Cancer Research, Sutton, United Kingdom
    Clin Cancer Res 18:5650-61. 2012
    ..We have therefore discovered a novel potent, highly selective, orally active ATP-competitive CHK1 inhibitor, CCT244747, and present its preclinical pharmacology and therapeutic activity...
  59. ncbi Roflumilast, an oral, once-daily phosphodiesterase 4 inhibitor, attenuates allergen-induced asthmatic reactions
    Emmerentia van Schalkwyk
    Department of Internal Medicine, University of Stellenbosch, Cape Town
    J Allergy Clin Immunol 116:292-8. 2005
    ..Roflumilast is an oral, once-daily inhibitor of phosphodiesterase type 4 that prevents the breakdown of cyclic adenosine monophosphate levels, leading to inhibition of proinflammatory signaling...
  60. ncbi Radiosynthesis of the candidate beta-amyloid radioligand [(11)C]AZD2184: Positron emission tomography examination and metabolite analysis in cynomolgus monkeys
    Jan D Andersson
    Karolinska Institutet, Department of Clinical Neuroscience, Stockholm, Sweden
    Synapse 64:733-41. 2010
    ..On the basis of the labeling chemistry and the results of the biological evaluation, we conclude that [(11)C]5 should be useful for routine clinical studies...
  61. pmc Symmetric double-headed aminopyridines, a novel strategy for potent and membrane-permeable inhibitors of neuronal nitric oxide synthase
    Fengtian Xue
    Department of Chemistry, Center for Molecular Innovation and Drug Discovery, Chemistry of Life Processes Institute, Northwestern University, 2145 Sheridan Road, Evanston, Illinois 60208 3113, United States
    J Med Chem 54:2039-48. 2011
    ..These compounds provide a basis for further development of novel, potent, isoform selective, and bioavailable inhibitors for nNOS...
  62. ncbi Inflammation does not precede or accompany the induction of preneoplastic lesions in the colon of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine-fed rats
    Dana Kühnel
    Nutritional Toxicology, Institute of Nutritional Science, University of Potsdam, Nuthetal, Germany
    Arch Toxicol 83:763-8. 2009
    ....
  63. ncbi 5-Amino-6-chloro-N-[(1-isobutylpiperidin-4-yl)methyl]-2-methylimidazo[1,2-alpha]pyridine-8-carboxamide (CJ-033,466), a novel and selective 5-hydroxytryptamine4 receptor partial agonist: pharmacological profile in vitro and gastroprokinetic effect in consc
    Tadayoshi Mikami
    Drug Safety Research and Development, Tokyo Laboratories, Pfizer Global Research and Development, Pfizer Inc, 3 22 7 Yoyogi, Shibuya, Tokyo 151 8589, Japan
    J Pharmacol Exp Ther 325:190-9. 2008
    ..Therefore, CJ-033,466 could be used to treat gastroparesis, providing better gastroprokinetics and reduced side effects mediated by the other receptors...
  64. ncbi Differential regulation of the mesoaccumbens dopamine circuit by serotonin2C receptors in the ventral tegmental area and the nucleus accumbens: an in vivo microdialysis study with cocaine
    Sylvia Navailles
    Unité Mixte de Recherche Centre National de la Recherche Scientifique UMR CNRS 5541, Universite Victor Segalen Bordeaux 2, Bordeaux Cedex, France
    Neuropsychopharmacology 33:237-46. 2008
    ....
  65. ncbi Pyrazolopyridines as a novel structural class of potent and selective PDE4 inhibitors
    J Nicole Hamblin
    GlaxoSmithKline Medicines Research Centre, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, UK
    Bioorg Med Chem Lett 18:4237-41. 2008
    ....
  66. pmc Roflumilast inhibits leukocyte-endothelial cell interactions, expression of adhesion molecules and microvascular permeability
    M J Sanz
    Department of Pharmacology, University of Valencia, Valencia, Spain
    Br J Pharmacol 152:481-92. 2007
    ..The present study addressed the effects of the investigational PDE4 inhibitor roflumilast on leukocyte-endothelial cell interactions and endothelial permeability in vivo and in vitro...
  67. ncbi Analgesic efficacy of flupirtine in primary care of patients with osteoporosis related pain. A multivariate analysis
    Johann D Ringe
    Medical Clinic IV, Leverkusen Medical Center, University of Cologne, Cologne, Germany
    Arzneimittelforschung 53:496-502. 2003
    ..The efficacy and tolerability of flupirtine (CAS 56995-20-1, Trancopal Dolo) up to 600 mg/day was investigated under daily practice conditions...
  68. pmc Biochemical and behavioural characterization of EMPA, a novel high-affinity, selective antagonist for the OX(2) receptor
    P Malherbe
    Discovery Research CNS, F Hoffmann La Roche Ltd, Basel, Switzerland
    Br J Pharmacol 156:1326-41. 2009
    ..Herein, we describe the in vitro and in vivo properties of a selective OX(2) receptor antagonist, N-ethyl-2-[(6-methoxy-pyridin-3-yl)-(toluene-2-sulphonyl)-amino]-N-pyridin-3-ylmethyl-acetamide (EMPA)...
  69. ncbi Efficacy and safety of roflumilast in the treatment of asthma
    Eric D Bateman
    Division of Pulmonology, Department of Medicine, University of Cape Town, South Africa
    Ann Allergy Asthma Immunol 96:679-86. 2006
    ..Roflumilast is an oral, once-daily phosphodiesterase type 4 inhibitor with anti-inflammatory activity in preclinical models of asthma and chronic obstructive pulmonary disease...
  70. ncbi Identification and characterisation of 2-aminopyridine inhibitors of checkpoint kinase 2
    Stephen Hilton
    Cancer Research UK Centre for Cancer Therapeutics, The Institute of Cancer Research, 15 Cotswold Road, Sutton, Surrey SM2 5NG, UK
    Bioorg Med Chem 18:707-18. 2010
    ..Compounds from this series showed activity in cell-based mechanistic assays for inhibition of CHK2...
  71. pmc Inhibition of the PtdIns(5) kinase PIKfyve disrupts intracellular replication of Salmonella
    Markus C Kerr
    Institute for Molecular Bioscience and ARC Centre of Excellence in Bioinformatics, The University of Queensland, St Lucia, Queensland, Australia
    EMBO J 29:1331-47. 2010
    ..Finally, although inhibition of PIKfyve in macrophages did inhibit Salmonella replication, it also appears to disrupt the macrophage's bactericidal response...
  72. ncbi Stimulation of 5-hydroxytryptamine (5-HT(2C) ) receptors in the ventrotegmental area inhibits stress-induced but not basal dopamine release in the rat prefrontal cortex
    Laura Pozzi
    Mario Negri Institute of Pharmacological Research, Via Eritrea 62, 20157 Milan, Italy
    J Neurochem 82:93-100. 2002
    ....
  73. ncbi Investigation of the in vitro metabolism of the analgesic flupirtine
    Karen Methling
    Institute of Pharmacy, University of Greifswald, Greifswald, Germany
    Drug Metab Dispos 37:479-93. 2009
    ..Incubations of human liver microsomes with flupirtine or the metabolite D13223 together with UDP-glucuronic acid gave two isomeric N-glucuronides in both cases...
  74. ncbi Effect of steady-state enoxacin on single-dose pharmacokinetics of roflumilast and roflumilast N-oxide
    Gezim Lahu
    Nycomed GmbH, Konstanz, Germany
    J Clin Pharmacol 51:586-93. 2011
    ..Roflumilast was well tolerated both alone and in combination with enoxacin. A weak interaction was shown between roflumilast and enoxacin, as mean tPDE4i increased by 25%, but is unlikely to have clinical relevance...
  75. pmc Effects of rifampicin on the pharmacokinetics of roflumilast and roflumilast N-oxide in healthy subjects
    Nassr Nassr
    Nycomed GmbH, 78467 Konstanz, Germany
    Br J Clin Pharmacol 68:580-7. 2009
    ..Roflumilast is metabolized by CYP3A4 and CYP1A2, with further involvement of CYP2C19 and extrahepatic CYP1A1. In vivo, roflumilast N-oxide contributes >90% to the total PDE4 inhibitory activity...
  76. ncbi Effect of fluvoxamine on the pharmacokinetics of roflumilast and roflumilast N-oxide
    Oliver von Richter
    Exploratory Medicine, ALTANA Pharma AG, Konstanz, Germany
    Clin Pharmacokinet 46:613-22. 2007
    ....
  77. ncbi Roflumilast fully prevents emphysema in mice chronically exposed to cigarette smoke
    Piero A Martorana
    Department of Physiopathology and Experimental Medicine, University of Siena, Via Aldo Moro 6, I 53100 Siena, Italy
    Am J Respir Crit Care Med 172:848-53. 2005
    ..There is a need for new agents capable of suppressing the inflammatory response in chronic obstructive pulmonary disease...
  78. ncbi Flupirtine shows functional NMDA receptor antagonism by enhancing Mg2+ block via activation of voltage independent potassium channels. Rapid communication
    J Kornhuber
    Department of Psychiatry, University of Gottingen, Federal Republic of Germany
    J Neural Transm 106:857-67. 1999
    ..This makes flupirtine the prototype of a clinically applicable substance group with analgesic, muscle-relaxant and neuroprotective properties...
  79. ncbi [Analgesic and muscle tonus normalizing effect of flupirtine retard in chronic back pain. Results of a standardized therapeutic evaluation applying objective methods for measuring pain pressure threshold, pain pressure tolerance and muscle tension]
    G H H Müller-Schwefe
    Regionales Schmerz und Palliativzentrum DGS, Goppingen
    MMW Fortschr Med 149:153-61. 2008
    ..Flupirtine retard (Katadolon S long) has provided such an option since 2006...
  80. pmc YM201636, an inhibitor of retroviral budding and PIKfyve-catalyzed PtdIns(3,5)P2 synthesis, halts glucose entry by insulin in adipocytes
    Ognian C Ikonomov
    Department of Physiology, Wayne State University School of Medicine, 540 E Canfield, Detroit, MI 48201, United States
    Biochem Biophys Res Commun 382:566-70. 2009
    ....
  81. ncbi Phosphodiesterase-4 inhibitors for asthma and chronic obstructive pulmonary disease
    Brian J Lipworth
    Department of Medicine and Therapeutics, Asthma and Allergy Research Group, University of Dundee, Ninewells Hospital and Medical School, Dundee DD1 9SY, UK
    Lancet 365:167-75. 2005
    ..Ultimately, clinicians will want to know whether PDE4 inhibitors are anything more than expensive "designer" theophylline, the archetypal non-selective phosphodiesterase inhibitor...
  82. 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...
  83. pmc A clinical evaluation of amlexanox oral adhesive pellicles in the treatment of recurrent aphthous stomatitis and comparison with amlexanox oral tablets: a randomized, placebo controlled, blinded, multicenter clinical trial
    Wenxia Meng
    State Key Laboratory of Oral Diseases, West China College of Stomatology, Sichuan University, Sichuan, PR China
    Trials 10:30. 2009
    ....
  84. ncbi Attenuation of methamphetamine induced dopaminergic neurotoxicity by flupirtine: microdialysis study on dopamine release and free radical generation
    M Gassen
    Eve Topf and National Parkinson s Foundation Centers of Excellence, Bruce Rappaport Family Research Institute, and Department of Pharmacology, Technion Faculty of Medicine, Haifa, Israel
    J Neural Transm 110:171-82. 2003
    ..This suggests that other mechanisms rather than dopamine metabolism and autoxidation, may contribute to methamphetamine neurotoxicity...
  85. 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...
  86. ncbi S100A13 is involved in the regulation of fibroblast growth factor-1 and p40 synaptotagmin-1 release in vitro
    C Mouta Carreira
    Center for Molecular Medicine, Maine Medical Center Research Institute, South Portland, Maine 04106, USA
    J Biol Chem 273:22224-31. 1998
    ....
  87. ncbi Phosphodiesterase type 4 inhibitors cause proinflammatory effects in vivo
    Kerryn McCluskie
    Department of Pharmacology, Theravance Inc, South San Francisco, California, USA
    J Pharmacol Exp Ther 319:468-76. 2006
    ..The proinflammatory cytokines KC and IL-8 therefore may provide surrogate biomarkers, both in preclinical animal models and in the clinic, to assess potential proinflammatory effects of this class of compounds...
  88. ncbi A phosphodiesterase 4 inhibitor inhibits matrix protein deposition in airways in vitro
    Janette K Burgess
    Department of Pharmacology, University of Sydney, NSW, Australia
    J Allergy Clin Immunol 118:649-57. 2006
    ..Airway smooth muscle (ASM) cells may contribute to airway remodeling through the release of growth factors, cytokines, and extracellular matrix (ECM) proteins. The effect of current asthma therapies on this release is not known...
  89. ncbi Combination therapy with flupirtine and opioid: open-label case series in the treatment of neuropathic pain associated with cancer
    Colin S Goodchild
    Department of Anaesthesia and Perioperative Medicine, Monash University, Clayton, Victoria, Australia
    Pain Med 9:939-49. 2008
    ..This study is a case series that was designed to provide data on the efficacy and the incidence and duration of adverse effects of flupirtine in the treatment of cancer-related neuropathic pain...
  90. ncbi Flupirtine blocks apoptosis in batten patient lymphoblasts and in human postmitotic CLN3- and CLN2-deficient neurons
    Sumeer Dhar
    Department of Pediatrics, Duke University Medical Center, Durham, NC 27710, USA
    Ann Neurol 51:448-66. 2002
    ..Flupirtine may be useful as a drug capable of halting the progression of neurodegenerative diseases caused by dysregulated apoptosis...
  91. ncbi No dose adjustment on coadministration of the PDE4 inhibitor roflumilast with a weak CYP3A, CYP1A2, and CYP2C19 inhibitor: an investigation using cimetidine
    Gabriele M Böhmer
    Department of Clinical Pharmacology, University Hospital of Tubingen, Tubingen, Germany
    J Clin Pharmacol 51:594-602. 2011
    ..These moderate changes indicate that dose adjustment of roflumilast is not required when coadministered with a weak inhibitor of CYP1A2, CYP3A, and CYP2C19, such as cimetidine...
  92. ncbi [Use of katadolon in the treatment of abuse headache]
    M V Naprienko
    Zh Nevrol Psikhiatr Im S S Korsakova 106:38-41. 2006
    ..The period of withdrawal from drug abuse was painless. An effect of treatment remained during 1 month after the withdrawal from the drug in 11 patients, 2 patients continued to receive katadolon...
  93. ncbi Effect of inhaled roflumilast on the prevention and resolution of allergen-induced late phase airflow obstruction in Brown Norway rats
    Richard W Chapman
    Schering Plough Research Institute, Pulmonary and Peripheral Neurobiology M S 1700, 2015 Galloping Hill Road, Kenilworth, NJ 07033, United States
    Eur J Pharmacol 571:215-21. 2007
    ..These results support the development of inhaled PDE4 inhibitors for the treatment of asthma and COPD, particularly for the improvement of lung function...
  94. ncbi Single-dose pharmacokinetics of roflumilast in children and adolescents
    Kathleen A Neville
    Department of Pediatrics, University of Missouri Kansas City and the Children s Mercy Hospitals and Clinics, 2401 Gillham Road, Kansas City, MO 64079, USA
    J Clin Pharmacol 48:978-85. 2008
    ..1 and 0.8 microg/L per 1 microg/kg dose for adolescents and children, respectively), pharmacokinetic parameters for roflumilast and roflumilast N-oxide were not different between age groups and were similar to adults...
  95. ncbi Roflumilast--an oral anti-inflammatory treatment for chronic obstructive pulmonary disease: a randomised controlled trial
    Klaus F Rabe
    Leiden University Medical Centre, Leiden, Netherlands
    Lancet 366:563-71. 2005
    ..There are few treatment options for the disease. This study assessed the efficacy and safety of roflumilast, a phosphodiesterase-4 inhibitor, in patients with moderate to severe COPD...
  96. ncbi Phosphodiesterase 4 inhibitors for the treatment of COPD
    Graham Sturton
    Bayer plc, Pharma Research, Stoke Court, Stoke Poges, Slough SL2 4LY, Berkshire, UK
    Chest 121:192S-196S. 2002
    ..The initial clinical data on the most advanced compound, cilomilast, were indeed encouraging. However, full knowledge of the therapeutic value of this novel compound class awaits the outcome of longer term clinical trials...
  97. ncbi Metal-free catalysts for the hydrolysis of RNA derived from guanidines, 2-aminopyridines, and 2-aminobenzimidazoles
    Ute Scheffer
    Institute for Organic Chemistry and Chemical Biology, Goethe University Frankfurt, Marie Curie Str 11, 60439 Frankfurt am Main, Germany
    J Am Chem Soc 127:2211-7. 2005
    ..Conjugates of 10b with antisense oligonucleotides or RNA binding peptides, therefore, will be promising candidates as site specific artificial ribonucleases...
  98. ncbi Treatment strategies for recurrent oral aphthous ulcers
    R W Barrons
    Clinical Pharmacy, Xavier University of Louisiana, 1 Drexel Street, New Orleans, LA 70125 1098, USA
    Am J Health Syst Pharm 58:41-50; quiz 51-3. 2001
    ..Thalidomide is effective but, because of its toxicity and cost, should be used only as an alternative to oral corticosteroids. RAU can be effectively managed with a variety of topical and systemic medications...
  99. pmc PDE4 inhibitors as potential therapeutic agents in the treatment of COPD-focus on roflumilast
    Victoria Boswell-Smith
    The Sackler Institute of Pulmonary Pharmacology, King s College London School of Biomedical and Health Sciences, King s College London, Guys Campus, UK
    Int J Chron Obstruct Pulmon Dis 2:121-9. 2007
    ..This review will discuss the current standing of PDE4 inhibitors like roflumilast as novel treatments for COPD and the potential for developing nonemetic anti-inflammatory drugs...
  100. ncbi Magnesium hydroxide/aluminium hydroxide-containing antacid does not affect the pharmacokinetics of the targeted phosphodiesterase 4 inhibitor roflumilast
    Nassr Nassr
    Department of Exploratory Medicine, ALTANA Pharma AG, Byk Gulden Str 2, 78467 Konstanz, Germany
    J Clin Pharmacol 47:660-6. 2007
  101. ncbi PDE4 inhibitors as new anti-inflammatory drugs: effects on cell trafficking and cell adhesion molecules expression
    Maria Jesus Sanz
    Department of Pharmacology, Faculty of Medicine, University of Valencia, Avenida Blasco Ibanez 15, E 46010 Valencia, Spain
    Pharmacol Ther 106:269-97. 2005
    ..These new drugs may also offer opportunities for treatment of other inflammatory diseases...

Research Grants40

  1. Principles of Therapy in Cerebellar Disease: Explorations in Ion Channel Mutants
    JOHN SAMUEL STAHL; Fiscal Year: 2013
    ..Results of these experiments will allow us to test published speculations that aminopyridines exert their beneficial effects by restoring normal Purkinje cell activity...
  2. CHEMISTRY SUPPORT SERVICES TO THE ENVIRONMENTAL TOXICOLOGY PROGRAM
    STEVE GRAVES; Fiscal Year: 2010
    ..Purity analysis for a planned aminopyridines subchronic gavage study is complete...
  3. CHEMISTRY SUPPORT SERVICES TO THE ENVIRONMENTAL TOXICOLOGY PROGRAM
    STEVE GRAVES; Fiscal Year: 2009
    ..A collection Alkylanilines were procured and purity determined in support of in vitro studies. Aminopyridines to be used in a 90-day gavage study were analyzed for purity...
  4. PROPERTIES OF THE INWARD RECTIFIER OF SKELETAL MUSCLE
    PAUL HOROWICZ; Fiscal Year: 1980
    ..e., Barium, quaternary ammonium ions, aminopyridines) will be also studied...
  5. TAS::75 0862::TAS - NTP TOXICOLOGIC POTENTIAL OF SELECTED TEST AGENTS
    LU TAYLOR; Fiscal Year: 2011
    Studies to evaluate Aminopyridines by Gavage in F344/NTac Rats and B6C3F1 Mice
  6. Phase II SBIR: WHI-07: A Novel Dual-Function Microbicide
    OSMOND D CRUZ; Fiscal Year: 2005
    ....
  7. Stampidine: A Novel Broad-Spectrum Anti-HIV Microbicide
    OSMOND D CRUZ; Fiscal Year: 2005
    ..Specific Aims 1 and 2 may provide the foundation for the clinical development of STAMP in Phase II studies as a safe, effective broad-spectrum anti-HIV microbicide without conception-inhibiting functions. ..
  8. Transmitter Repletion: Key to Phrenic-Diaphragm Function
    Erik van Lunteren; Fiscal Year: 2005
    ..These studies may lead to novel therapeutic approaches to respiratory muscle impairment and resulting hypercapnic respiratory failure for conditions which produce neuromuscular junction dysfunction. ..
  9. Vanadocenes as a New Class of Spermicidal Drugs
    OSMOND D CRUZ; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  10. NOVEL CONTRACEPTIVES WITH ANTI-HIV ACTIVITY
    OSMOND D CRUZ; Fiscal Year: 2001
    ..The preclinical data on in vivo efficacies of WHI-05 and WHI-07 will be essential to further explore the utility of these novel drugs for clinical studies in human patients. ..
  11. PHI-443: Novel Non-Spermicidal Anti-HIV Microbicide
    OSMOND D CRUZ; Fiscal Year: 2003
    ..Specific Aims 1 and 2 may provide the foundation for the clinical development of PHI-443 in Phase II studies as a safe, effective broad-spectrum anti-HIV microbicide without conception-inhibiting functions. ..
  12. METVAN: A Novel Anticancer Agent
    OSMOND D CRUZ; Fiscal Year: 2003
    ..The knowledge gained from these studies described under Specific Aims 1-2 is expected to facilitate the design of innovative treatment regimens employing METVAN for metastatic breast cancer and brain tumor patients. ..
  13. PHI 346: A Novel Dual-Function Microbicide
    OSMOND D CRUZ; Fiscal Year: 2003
    ..Following successful completion of the Phase I in vivo efficacy studies, gel formulation of PHI-346 will be further explored as a vaginal dual-function microbicide in Phase II. ..
  14. FLP-102: Rationally Engineered Antiviral Protein
    OSMOND D CRUZ; Fiscal Year: 2003
    ..The preclinical data on FLP-102 will be essential to further explore the utility of this novel recombinant PAP mutant for Phase II. ..
  15. Joint Action Analysis of Poly-drug Withdrawal
    Robert Raffa; Fiscal Year: 2006
    ..g., electrophysiologic or molecular biology techniques. An improved understanding of how withdrawal is influenced by poly-drug abuse could lead to development of enhanced clinical treatment. ..
  16. The amygdaloid 5-HT2C receptor in anxiety-like behavior
    Qian Li; Fiscal Year: 2006
    ..Furthermore, the proposed studies have a high potential of leading to the development of novel drugs to treat anxiety disorders. ..
  17. Iron and Vitamin E in Childhood HIV-Associated Renal Disease
    Patricio Ray; Fiscal Year: 2006
    ..The proposed studies should have a substantial impact on the goals of the National Center for Complementary and Alternative Medicine and NIH, according to the program announcement PA-02-124. [unreadable] [unreadable]..
  18. LUNG HEALTH STUDY--LONG TERM FOLLOW UP
    Donald Tashkin; Fiscal Year: 2002
    ..All ten of the original LHS clinical centers plan to participate in this study. To minimize bias, all surviving participants of the LHS will be invited to participate, giving a potential sample size of 5600. ..
  19. CB1 Modulation of Opioid Peptides and Ethanol Intake
    Loren Parsons; Fiscal Year: 2008
    ..abstract_text> ..
  20. Distal Lung Inflammation Effect on Asthma Exacerbations
    Donald Tashkin; Fiscal Year: 2008
    ..This study has the potential to clarify the contribution of the "silent zone" to the persistent morbidity encountered with asthma. ..
  21. Novel Animal Model System of AIDS-Kaposi Sarcoma
    Patricio Ray; Fiscal Year: 2005
    ....
  22. COCAINE REWARD AND 5 HT 1B RECEPTORS--NEURAL MECHANISMS
    Loren Parsons; Fiscal Year: 2002
    ....
  23. SELECTIVE SEROTONERGIC AGENTS
    RICHARD GLENNON; Fiscal Year: 2004
    ..Radioligand binding and functional assays will be conducted. The 5-HT1F ligand is not selective; we propose to explore its structure-activity relationships and functional activity in an attempt to develop a 5-HT1F-selective ligand. ..
  24. SCLERODERMA LUNG STUDY
    Donald Tashkin; Fiscal Year: 2003
    ..abstract_text> ..
  25. Endocannabinoids and cue-induced drug-seeking behavior
    Loren Parsons; Fiscal Year: 2006
    ..unreadable] [unreadable]..
  26. Effects of Chronic THC in Adolescence
    Peter J Winsauer; Fiscal Year: 2010
    ..Together, data from these experiments will demonstrate how drug abuse and hormonal status during adolescence may permanently alter brain function and the liability of subsequent abuse of A9-THC. ..
  27. CHEMICAL/BEHAVIORAL STUDIES ON HALLUCINOGENIC AGENTS
    RICHARD GLENNON; Fiscal Year: 2007
    ..This will eventually lead to a better understanding of abuse prevention and treatment modalities. ..
  28. A Thermo Electron LTQ Mass Spectrometer
    Joseph Zaia; Fiscal Year: 2006
    ..The salary for the instrument operator will be provided by the Dean of BU School of Medicine. [unreadable] [unreadable]..
  29. 5-HTIB RECEPTORS AND MECHANISMS OF ETHANOL REINFORCEMENT
    Loren Parsons; Fiscal Year: 2005
    ..abstract_text> ..
  30. Limbic-cortical involvement in drug seeking
    Janet Neisewander; Fiscal Year: 2006
    ..The findings may be useful for developing behavioral and pharmacological treatments for cocaine dependence. ..
  31. EFFECTS OF DIOXINS (TCDD) ON CARDIAC ION CHANNELS
    Desuo Wang; Fiscal Year: 2003
    ....
  32. Viral neuropathology neuropeptides and epilepsy
    Marylou Solbrig; Fiscal Year: 2005
    ....
  33. BEHAVIORAL & PHARMACOLOGICAL ANALYSIS OF DRUGS OF ABUSE
    JERROLD WINTER; Fiscal Year: 2005
    ..abstract_text> ..
  34. Behavioral and Pharmacological Analysis of Drugs of Abuse
    JERROLD WINTER; Fiscal Year: 2008
    ..This likelihood coupled with continued interest in the therapeutic use of agents such as psilocybin makes a detailed pharmacological assessment of these drugs of utmost importance. ..
  35. Drugs as conditioned reinforcers and/or enhancers of social reward in adolescents
    Janet Neisewander; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable] [unreadable]..
  36. 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. ..
  37. AMBIENT PARTICULATE MATTERS POISON CARDIAC ION CHANNELS
    Desuo Wang; Fiscal Year: 2005
    ....
  38. CNS VIRAL INJURY AND VULNERABILITY TO OPIATE DRUG ABUSE
    Marylou Solbrig; Fiscal Year: 2002
    ..At the conclusion of the grant period, the requisite skills in behavioral pharmacology, neuropharmacology and molecular biology for continued work in the study and treatment of drug addiction will have been acquired by the candidate. ..
  39. Glycosaminoglycan-Protein Binding
    Joseph Zaia; Fiscal Year: 2006
    ..abstract_text> ..