- 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...
- 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...
- The preclinical pharmacology of roflumilast--a selective, oral phosphodiesterase 4 inhibitor in development for chronic obstructive pulmonary disease
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...
- Efficacy and safety of levomilnacipran sustained release in moderate to severe major depressive disorder: a randomized, double-blind, placebo-controlled, proof-of-concept study
Stuart A Montgomery
Imperial College School of Medicine, University of London, London, United Kingdom
J Clin Psychiatry 74:363-9. 2013
..To investigate the efficacy and safety of levomilnacipran sustained release (SR), an antidepressant candidate in late-stage development, in major depressive disorder (MDD)...
- 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...
- Efficacy and safety of levomilnacipran sustained release 40 mg, 80 mg, or 120 mg in major depressive disorder: a phase 3, randomized, double-blind, placebo-controlled study
Gregory M Asnis
Department of Psychiatry and Behavioral Sciences, Albert Einstein College of Medicine, Montefiore Medical Center, 111 East 210th St, Bronx, NY 10467, USA
J Clin Psychiatry 74:242-8. 2013
- Levomilnacipran (F2695), a norepinephrine-preferring SNRI: profile in vitro and in models of depression and anxiety
A L Auclair
Neuropsychopharmacology Division, Centre de Recherche Pierre Fabre, 17 avenue Jean Moulin, 81106 Castres, France
Neuropharmacology 70:338-47. 2013
..It is efficacious in models of anti-depressive/anti-stress activity, with minimal potential for locomotor side effects...
- 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...
- 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...
- Characterization and analysis of the cotton cyclopropane fatty acid synthase family and their contribution to cyclopropane fatty acid synthesis
Xiao Hong Yu
Department of Biochemistry and Cell Biology, Stony Brook University, NY, USA
BMC Plant Biol 11:97. 2011
- Roflumilast N-oxide, a PDE4 inhibitor, improves cilia motility and ciliated human bronchial epithelial cells compromised by cigarette smoke in vitro
Research Unit, University General Hospital Consortium, Valencia, Spain
Br J Pharmacol 166:2243-62. 2012
- Monoamine-dependent, opioid-independent antihypersensitivity effects of intrathecally administered milnacipran, a serotonin noradrenaline reuptake inhibitor, in a postoperative pain model in rats
Department of Anesthesiology, Gunma University Graduate School of Medicine, 3 39 22 Showa, Maebashi, Gunma 371 8511, Japan
J Pharmacol Exp Ther 334:1059-65. 2010
..Combined administration of an SNRI with morphine might be a promising treatment to suppress postoperative hypersensitivity...
- Roflumilast inhibits the release of chemokines and TNF-α from human lung macrophages stimulated with lipopolysaccharide
Laboratory of Pulmonary Pharmacology UPRES EA220, Foch Hospital, University Versailles Saint Quentin, Suresnes, France
Br J Pharmacol 165:1877-90. 2012
- Cost-effectiveness of available treatment options for patients suffering from severe COPD in the UK: a fully incremental analysis
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...
- Towards selective antagonists of T-type calcium channels: design, characterization and potential applications of NNC 55-0396
Department of Pharmacology SL 83, Tulane University Health Science Center, 1430 Tulane Avenue, New Orleans, LA 70112, USA
Cardiovasc Drug Rev 23:173-96. 2005
..We conclude that NNC 55-0396, by virtue of its modified structure, does not produce the metabolite that causes inhibition of L-type Ca2+ channel channels, thus rendering it more selective to T-type Ca2+ channels...
- CHF5074, a novel gamma-secretase modulator, restores hippocampal neurogenesis potential and reverses contextual memory deficit in a transgenic mouse model of Alzheimer's disease
Bruno P Imbimbo
Research and Development, Chiesi Farmaceutici, Parma, Italy
J Alzheimers Dis 20:159-73. 2010
..040). These effects were associated to a complete reversal of contextual memory deficit (p=0.006). Contextual memory significantly correlated with synaptophysin immunoreactivity in the cortex (r=0.548, p=0.0038)...
- 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
- Membrane cyclopropane fatty acid content is a major factor in acid resistance of Escherichia coli
Y Y Chang
Department of Microbiology, University of Illinois, Urbana 61801, USA
Mol Microbiol 33:249-59. 1999
..Much, but not all, of this variability can be explained by the partially or totally defective RpoS alleles carried by many strains...
- 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...
- 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...
- The monoamine-mediated antiallodynic effects of intrathecally administered milnacipran, a serotonin noradrenaline reuptake inhibitor, in a rat model of neuropathic pain
Department of Anesthesiology, Gunma University Graduate School of Medicine, 3 39 22 Showa, Maebashi, Gunma 371 8511, Japan
Anesth Analg 100:1406-10, table of contents. 2005
..These findings suggest that simultaneous inhibition of serotonin and noradrenaline reuptake in the spinal cord is essential to mediate antiallodynic effects. Milnacipran might be effective for suppression of neuropathic pain...
- 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...
- The γ-secretase modulator CHF5074 reduces the accumulation of native hyperphosphorylated tau in a transgenic mouse model of Alzheimer's disease
Division of Pharmacology and Experimental Therapeutics, Department of Biomedical Sciences and Biotechnologies, School of Medicine, University of Brescia and Istituto Nazionale di Neuroscienze Brescia, Italy
J Mol Neurosci 45:22-31. 2011
..Our data show that the novel γ-secretase modulator CHF5074 can fully reverse β-amyloid-associated tau pathology, thus representing a promising therapeutic agent for AD...
- Pd(II)-catalyzed enantioselective C-H activation of cyclopropanes
Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA
J Am Chem Soc 133:19598-601. 2011
..of novel mono-N-protected amino acid ligands for Pd(II)-catalyzed enantioselective C-H activation of cyclopropanes. A diverse range of organoboron reagents can be used as coupling partners, and the reaction proceeds under ..
- Ethylene-induced modulation of genes associated with the ethylene signalling pathway in ripening kiwifruit
Xue Ren Yin
Laboratory of Fruit Molecular Physiology and Biotechnology The State Agriculture Ministry Laboratory of Horticultural Plant Growth, Development and Biotechnology, Zhejiang University, Huajiachi Campus, Hangzhou 310029, PR China
J Exp Bot 59:2097-108. 2008
..The ethylene-induced down-regulation of AdETR1 suggests that it may have a role in sensing ethylene and transmitting this response to other members of the receptor family, thus activating the signal transduction pathway...
- Perinatal kynurenine 3-hydroxylase inhibition in rodents: pathophysiological implications
Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, Maryland 21228, USA
J Neurosci Res 85:845-54. 2007
..Selective inhibitors of this enzyme may therefore provide neuroprotection in newborns and will also be useful for the experimental evaluation of the long-term effects of perinatal KP impairment...
- Impairment of hippocampal mossy fiber LTD in mice lacking mGluR2
Department of Biological Sciences, Kyoto University Faculty of Medicine, Kyoto 606, Japan
Science 273:645-7. 1996
..The mutant mice performed normally in water maze learning tasks. Thus, the presynaptic mGluR2 is essential for inducing LTD at the mossy fiber-CA3 synapses, but this hippocampal LTD does not seem to be required for spatial learning...
- The γ-secretase modulator CHF5074 restores memory and hippocampal synaptic plasticity in plaque-free Tg2576 mice
Laboratory of Biology of Neurodegenerative Disorders, Department of Neuroscience, Mario Negri Institute for Pharmacological Research, Milan, Italy
J Alzheimers Dis 24:799-816. 2011
..We conclude that the beneficial effects of CHF5074 treatment in young transgenic mice occurred at a stage that precedes plaque formation and were associated with a reduction in intraneuronal AβPP/Aβ and hyperphosphorylated tau...
- LPS-induced lung inflammation in marmoset monkeys - an acute model for anti-inflammatory drug testing
Airway Research, Fraunhofer Institute for Toxicology and Experimental Medicine, Hannover, Germany
PLoS ONE 7:e43709. 2012
- Secretase-independent and RhoGTPase/PAK/ERK-dependent regulation of cytoskeleton dynamics in astrocytes by NSAIDs and derivatives
Mathieu P Lichtenstein
Institut de Neurociènces, Universitat Autonoma de Barcelona, Spain
J Alzheimers Dis 22:1135-55. 2010
- Roflumilast, a phosphodiesterase 4 inhibitor, alleviates bleomycin-induced lung injury
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...
- Peripheral nerve injury sensitizes the response to visceral distension but not its inhibition by the antidepressant milnacipran
Sang Wook Shin
Department of Anesthesiology, Wake Forest University School of Medicine, Winston Salem, North Carolina 27157, USA
Anesthesiology 100:671-5. 2004
- Changes in membrane lipid composition in ethanol- and acid-adapted Oenococcus oeni cells: characterization of the cfa gene by heterologous complementation
Laboratoire Recherche En Vigne et Vin, Universite de Bourgogne, Institut Universitaire de la Vigne et du Vin Jules Guyot, 1, Rue Claude Ladrey Campus Montmuzard, BP27877, F 21078 Dijon, France
Microbiology 154:2611-9. 2008
..oeni. In spite of this partial complementation, the complemented strain of E. coli totally recovered its viability after ethanol shock (10 %, v/v) whereas its viability was only partly recovered after an acid shock at pH 3.0...
- 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...
- 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...
- Acid habituation of Escherichia coli and the potential role of cyclopropane fatty acids in low pH tolerance
J L Brown
Department of Agricultural Science, University of Tasmania, Australia brown
Int J Food Microbiol 37:163-73. 1997
..The results presented illustrate the remarkable capacity of E. coli to adapt to environmental challenges, and have significant implications for the survival of spoilage and pathogenic bacteria, and hence for food safety...
- A phosphodiesterase 4 inhibitor, roflumilast N-oxide, inhibits human lung fibroblast functions in vitro
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...
- Carbocyclic fatty acids in plants: biochemical and molecular genetic characterization of cyclopropane fatty acid synthesis of Sterculiafoetida
Department of Plant Biology, Michigan State University, East Lansing, MI 48824, USA
Proc Natl Acad Sci U S A 99:7172-7. 2002
..Together, a CPA-FA synthase was identified from S. foetida, and the pathway in higher plants that produce carbocyclic fatty acids was defined as by transfer of C(1) units, most likely from S-adenosylmethionine to oleate...
- CHF5074, a novel gamma-secretase modulator, attenuates brain beta-amyloid pathology and learning deficit in a mouse model of Alzheimer's disease
B P Imbimbo
Research and Development, Chiesi Farmaceutici, Via Palermo, Parma, Italy
Br J Pharmacol 156:982-93. 2009
- Population pharmacokinetic modelling of roflumilast and roflumilast N-oxide by total phosphodiesterase-4 inhibitory activity and development of a population pharmacodynamic-adverse event model
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...
- Deletion of kasB in Mycobacterium tuberculosis causes loss of acid-fastness and subclinical latent tuberculosis in immunocompetent mice
Howard Hughes Medical Institute, Albert Einstein College of Medicine, Bronx, NY 10461, USA
Proc Natl Acad Sci U S A 104:5157-62. 2007
..This long-term persistence of DeltakasB represents a model for studying latent M. tuberculosis infections and suggests that this attenuated strain may represent a valuable vaccine candidate against tuberculosis...
- Trans-cyclopropanation of mycolic acids on trehalose dimycolate suppresses Mycobacterium tuberculosis -induced inflammation and virulence
Immunology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
J Clin Invest 116:1660-7. 2006
..tuberculosis-induced inflammation and virulence. In addition, cyclopropane stereochemistries on mycolic acids interact directly with host cells to both positively and negatively influence host innate immune activation...
- In vitro and in vivo profiling of CHF5022 and CHF5074 Two beta-amyloid1-42 lowering agents
Bruno P Imbimbo
Research and Development Department, Chiesi Farmaceutici, Via Palermo 26 A, 43100 Parma, Italy
Pharmacol Res 55:318-28. 2007
..105) with CHF5022 concentration in the brain. CHF5022 and CHF5074 thus appear to have a promising in vitro and in vivo profile. This warrants further evaluation of their long-term effects on Abeta brain pathology...
- Effects of rifampicin on the pharmacokinetics of roflumilast and roflumilast N-oxide in healthy subjects
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...
- Stereospecific formation of the (R)-gamma-hydroxytrimethylene interstrand N2-dG:N2-dG cross-link arising from the gamma-OH-1,N2-propano-2'-deoxyguanosine adduct in the 5'-CpG-3' DNA sequence
Department of Chemistry and Center in Molecular Toxicology, Vanderbilt University, Nashville, Tennessee 37235, USA
J Am Chem Soc 131:8416-24. 2009
..The formation of this hydrogen bond may, in part, explain the thermal stability of this carbinolamine interstrand cross-link and the stereochemical preference for the (R) configuration of the cross-link...
- Novel cyclopropane fatty acids from the phospholipids of the Caribbean sponge Pseudospongosorites suberitoides
Néstor M Carballeira
Department of Chemistry, University of Puerto Rico, Rio Piedras Campus, PO Box 23346, San Juan, 00931 3346 Puerto Rico
Lipids 42:519-24. 2007
..The novel cyclopropyl fatty acids could have originated from the phospholipids of a cyanobacterium living in symbiosis with the sponge...
- 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...
- Vinylcyclopropane derivatives in transition-metal-catalyzed cycloadditions for the synthesis of carbocyclic compounds
College of Chemistry, Peking University, Beijing 100871, China
J Org Chem 78:6842-8. 2013
..A tabular summary of applications of the VCP cycloadditions in natural product synthesis is also presented. ..
- 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...
- Rh(I)-catalyzed [(3 + 2) + 1] cycloaddition of 1-yne/ene-vinylcyclopropanes and CO: homologous Pauson-Khand reaction and total synthesis of (+/-)-alpha-agarofuran
Beijing National Laboratory of Molecular Sciences BNLMS, Key Laboratory of Bioorganic Chemistry and Molecular Engineering, College of Chemistry, Peking University, Beijing 100871, China
Org Lett 12:2528-31. 2010
- 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...
- Isolation of C₁₁ compounds and a cyclopropane fatty acid from an Okinawan ascidian, Diplosoma sp
Department of Chemistry, Biology and Marine Science, University of the Ryukyus, Nishihara cho Okinawa 903 0123, Japan
Molecules 16:9972-82. 2011
..The structures of 1-5 were determined by spectroscopic analysis and/or synthesis. Compound 1 inhibited the division of fertilized sea urchin eggs and compound 4 showed mild cytotoxity against HCT116 cells (human colorectal cancer cell)...
- Carbon dioxide action on ethylene biosynthesis of preclimacteric and climacteric pear fruit
Hans P J de Wild
Agrotechnological Research Institute ATO, PO Box 17, 6700 AA Wageningen, The Netherlands
J Exp Bot 54:1537-44. 2003
..Kinetic parameters derived from the models point to the conversion from ACC to ethylene by ACC oxidase as a possible action site for CO2 inhibition...
- 1-(3',4'-Dichloro-2-fluoro[1,1'-biphenyl]-4-yl)-cyclopropanecarboxylic acid (CHF5074), a novel gamma-secretase modulator, reduces brain beta-amyloid pathology in a transgenic mouse model of Alzheimer's disease without causing peripheral toxicity
Bruno P Imbimbo
Research and Development, Chiesi Farmaceutici, Via Palermo 26 A, 43100 Parma, Italy
J Pharmacol Exp Ther 323:822-30. 2007
..CHF5074 is therefore a promising therapeutic agent for Alzheimer's disease...
- Silver-promoted, palladium-catalyzed direct arylation of cyclopropanes: facile access to spiro 3,3'-cyclopropyl oxindoles
Carolyn L Ladd
Centre in Green Chemistry and Catalysis, Department of Chemistry, Universite de Montreal, P O Box 6128 Station Downtown, Montreal, Quebec, H3C 3J7, Canada
Org Lett 15:1350-3. 2013
..The kinetic isotope effect was determined and epimerization studies were conducted, suggesting that the formation of a putative Pd-enolate is not operative and that the reaction proceeds via a C-H arylation pathway...
- Roflumilast-N-oxide induces surfactant protein expression in human alveolar epithelial cells type II
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...
- Frequency facilitation at mossy fiber-CA3 synapses of freely behaving rats is regulated by adenosine A1 receptors
Department of Experimental Neurophysiology, Medical Faculty, Ruhr University Bochum, 44780 Bochum, Germany
J Neurosci 28:4836-40. 2008
- 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...
- Phosphodiesterase type 4 inhibitors cause proinflammatory effects in vivo
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...
- Phospholipid modifications in bacteria
John E Cronan
Department of Microbiology, University of Illinois, B103 Chemical and Life Sciences Laboratory, 601 South Goodwin Avenue, Urbana, Illinois 61801, USA
Curr Opin Microbiol 5:202-5. 2002
..Cyclopropanation has been shown to play a role in Mycobacterium tuberculosis pathogenesis and, in Escherichia coli, plays an important role in resistance to acidic conditions...
- Inhibition of the ethylene response by 1-MCP in tomato suggests that polyamines are not involved in delaying ripening, but may moderate the rate of ripening or over-ripening
Department of Plant Biology, Cornell University, Ithaca, NY 14853, USA
J Exp Bot 57:3313-25. 2006
..No effect of treatment on ornithine decarboxylase activity was detected. Polyamines are thus not directly associated with a delay in tomato fruit ripening, but may prolong the fully-ripe stage before the fruit tissues undergo senescence...
- Cyclopropane ring formation in membrane lipids of bacteria
D W Grogan
Department of Biological Sciences, University of Cincinnati, Ohio 45221 0006, USA
Microbiol Mol Biol Rev 61:429-41. 1997
- Cloning and functional analysis of 9-cis-epoxycarotenoid dioxygenase (NCED) genes encoding a key enzyme during abscisic acid biosynthesis from peach and grape fruits
College of Agronomy and Biotechnology, China Agricultural University, Beijing 100094, China
J Plant Physiol 166:1241-52. 2009
- Differential expression and internal feedback regulation of 1-aminocyclopropane-1-carboxylate synthase, 1-aminocyclopropane-1-carboxylate oxidase, and ethylene receptor genes in tomato fruit during development and ripening
Laboratory of Postharvest Agriculture, Faculty of Agriculture, Okayama University, Tsushima, Okayama, 700 8530 Japan
Plant Physiol 118:1295-305. 1998
..This transition from system 1 to system 2 ethylene production might be related to the accumulated level of NR mRNA...
- 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...
- 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...
- The efficacy and safety of milnacipran for treatment of fibromyalgia. a randomized, double-blind, placebo-controlled trial
Philip J Mease
Seattle Rheumatology Associates, 1101 Madison Street, Suite 1000, Seattle, WA 98104, USA
J Rheumatol 36:398-409. 2009
..To evaluate the safety and efficacy of milnacipran, a dual norepinephrine and serotonin reuptake inhibitor, in the treatment of fibromyalgia (FM)...
- Presynaptic inhibition of corticothalamic feedback by metabotropic glutamate receptors
Georgia M Alexander
Neuroscience Program, Wake Forest University School of Medicine, Medical Center Blvd Winston Salem, NC 27157, USA
J Neurophysiol 94:163-75. 2005
..This presynaptic inhibition may partially mute sensory feedback and prevent reentrant excitation from initiating abnormal thalamic rhythms...
- 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...
- The discovery and development of compounds counteracting ethylene at the receptor level
Edward C Sisler
Department of Molecular and Structural Biochemistry, North Carolina State University, Raleigh, North Carolina 27695 7722, USA
Biotechnol Adv 24:357-67. 2006
..1-MCP is likely to remain a primary means of controlling ethylene responses for the immediate future...
- Stereocontrolled synthesis of 3-(trans-2-aminocyclopropyl)alanine, a key component of belactosin A
Department of Chemistry, Imperial College London, South Kensington, London SW7 2AZ, UK
Org Lett 5:2331-4. 2003
..reaction: see text]..
- Ethylene is required for both the initiation and progression of softening in pear (Pyrus communis L.) fruit
Graduate School of Natural Science and Technology, Okayama University, Tsushima, Okayama 700 8530, Japan
J Exp Bot 54:771-9. 2003
..The results suggest that ethylene is required for PGs expression even in the late ripening stage, but not for EGases...
- 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...
- Gold(I)-catalyzed stereoselective olefin cyclopropanation
Magnus J Johansson
Department of Chemistry, University of California, Berkeley, California 94720, USA
J Am Chem Soc 127:18002-3. 2005
..This reaction provided the basis for the use of a DTBM-SEGPHOS gold(I) complex as a catalyst in the enantioselective (up to 94% ee) preparation of vinyl cyclopropanes with high cis-selectivity.
- Involvement of negative feedback regulation in wound-induced ethylene synthesis in 'Saijo' persimmon
Qiao Lin Zheng
The United Graduate School of Agricultural Sciences, Tottori University, Japan
J Agric Food Chem 54:5875-9. 2006
..Out of accord with DK-ACO1 gene expression, ACC oxidase activity was enhanced 48 h after wounding in 1-MCP pretreated tissues, reaching a peak 1.5-fold higher than that in control tissues at 60 h...
- The oral, once-daily phosphodiesterase 4 inhibitor roflumilast lacks relevant pharmacokinetic interactions with inhaled budesonide
ALTANA Pharma AG, Konstanz, Germany
J Clin Pharmacol 47:1005-13. 2007
..67, 1.50). Coadministration of roflumilast and budesonide did not alter the steady-state disposition of each other and did not affect safety and tolerability of either drug...
- 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
- 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...
- Differential feedback regulation of ethylene biosynthesis in pulp and peel tissues of banana fruit
Faculty of Agriculture, Okayama University, Tsushima, Okayama, 700 8530 Japan
J Exp Bot 58:1047-57. 2007
..This differential regulation by ethylene in pulp and peel tissues was also observed for MA-PL, MA-Exp, and MA-MADS genes...
- Transcriptional regulation of ethylene receptor and CTR genes involved in ethylene-induced flower opening in cut rose (Rosa hybrida) cv. Samantha
Department of Ornamental Horticulture, China Agricultural University, Beijing 100094, China
J Exp Bot 57:2763-73. 2006
..Samantha, and that continued ethylene perception results in flower opening. Ethylene may regulate flower opening mainly through expression of two ethylene receptor genes (Rh-ETR1 and Rh-ETR3) and two CTR (Rh-CTR1 and Rh-CTR2) genes...
- 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
- 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...
- Metabotropic glutamate receptors stimulate phospholipase D via different pathways in the adult and neonate rat hippocampus
Dipartimento di Farmacologia Preclinica e Clinica, , Italy
Neurochem Res 26:1151-5. 2001
..Our results lend support to the hypothesis that glutamatergic activation of PLD in the rat hippocampus is developmentally regulated...
- Expression of vascular endothelial growth factor, apoptosis inhibitors (survivin and p16) and CCL27 in alopecia areata before and after diphencyprone treatment: an immunohistochemical study
Clinica Dermatologica, Universita Politecnica delle Marche, Ospedale Regionale, Via Conca 20, 60020 Torrette, Ancona, Italy
Br J Dermatol 150:940-8. 2004
..The cutaneous lymphocyte-associated antigen (CLA) and the skin-associated chemokine CCL27 highlight an important role for epithelial cells in controlling homeostatic lymphocyte trafficking...
- PDE4 inhibitors: a review of current developments (2005 - 2009)
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...
- Laboratory and field evaluation of spatial repellency with metofluthrin-impregnated paper strip against mosquitoes in Lombok Island, Indonesia
Department of Vector Ecology and Environment, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Nagasaki 852 8523, Japan
J Am Mosq Control Assoc 20:292-8. 2004
..Metofluthrin treatment reduced mosquito collection by >80% during the 1st 4 weeks. However, repellency seemed to reduce with the loss of metofluthrin by evaporation within 6 wk after treatment...
- Evidence that phospholipase D activation prevents group I mGluR-induced persistent prolongation of epileptiform bursts
Marjorie J Rico
Neural and Behavioral Science Program, School of Graduate Studies, State University of New York Downstate Medical Center, Brooklyn, New York 11203, USA
J Neurophysiol 91:2385-8. 2004
..Hence, PLD activation with CSA may prevent the synthesis of a protein critical for the induction of group I mGluR-mediated epileptogenesis...
- Effect of steady-state enoxacin on single-dose pharmacokinetics of roflumilast and roflumilast N-oxide
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...
- 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...
- MMAS-1, the branch point between cis- and trans-cyclopropane-containing oxygenated mycolates in Mycobacterium tuberculosis
Tuberculosis Research Unit, Laboratory of Intracellular Parasites, Rocky Mountain Laboratories, NIAID, National Institutes of Health, Hamilton, Montana 59840, USA
J Biol Chem 272:10041-9. 1997
- Roflumilast, a phosphodiesterase 4 inhibitor, reduces airway hyperresponsiveness after allergen challenge
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...
- The use of topical diphenylcyclopropenone for the treatment of extensive alopecia areata
Department of Dermatology, University of L Aquila, Italy
J Am Acad Dermatol 44:73-6. 2001
..Highly variable results of topical diphenylcyclopropenone (DPCP) in the treatment of alopecia areata have been reported so far...
- Identification of a gene involved in the biosynthesis of cyclopropanated mycolic acids in Mycobacterium tuberculosis
Laboratory of Intracellular Parasites, National Institutes for Allergy and Infectious Diseases, Rocky Mountain Laboratories, Hamilton, MT 59840, USA
Proc Natl Acad Sci U S A 92:6630-4. 1995
..M. smegmatis overexpressing the cma1 gene product significantly resist killing by hydrogen peroxide, suggesting that this modification may be an important adaptation of slow-growing mycobacteria to oxidative stress...
- Lack of a pharmacokinetic interaction between steady-state roflumilast and single-dose midazolam in healthy subjects
ALTANA Pharma AG, 78467 Konstanz, Germany
Br J Clin Pharmacol 63:365-70. 2007
..The aim of this study was to investigate the effects of roflumilast, an investigational PDE4 inhibitor for the treatment of COPD and asthma, on the pharmacokinetics of the CYP3A probe drug midazolam and its major metabolites...
- Steady-state pharmacokinetics of roflumilast and roflumilast N-oxide in patients with mild and moderate liver cirrhosis
Exploratory Medicine, ALTANA Pharma AG, Konstanz, Germany
Clin Pharmacokinet 46:403-16. 2007
..Roflumilast is being developed for the treatment of inflammatory airway diseases such as chronic obstructive pulmonary disease and asthma...
- Restoration of hair growth with topical diphencyprone in mouse and rat models of alopecia areata
Division of Dermatology, University of British Columbia, Vancouver Hospital and Health Sciences Center, 835 W 10th Avenue, Vancouver, BC, Canada V5Z 4E8
J Am Acad Dermatol 49:1013-9. 2003
..The contact sensitizer, diphencyprone (DPCP), is one of the most effective therapies for the more severe forms of alopecia areata (AA)...
- Diphenylcyclopropenone treatment of alopecia areata induces apoptosis of perifollicular lymphocytes
Dept of Dermatology, Philipp University, Deutschhausstrasse 9, 35033 Marburg, Germany
Eur J Dermatol 16:537-42. 2006
..In addition the replacement with newly activated autoreactive T-cells might be impaired due to a DCP-mediated hindrance of APC emigration...
- Roflumilast, a once-daily oral phosphodiesterase 4 inhibitor, lacks relevant pharmacokinetic interactions with inhaled salbutamol when co-administered in healthy subjects
T D Bethke
ALTANA Pharma AG, Konstanz, Germany
Int J Clin Pharmacol Ther 44:572-9. 2006
..Therefore, this study investigated the pharmacokinetic characteristics of roflumilast and its pharmacodynamically active metabolite roflumilast N-oxide when co-administered with orally inhaled salbutamol in healthy subjects...
- The biosynthesis of cyclopropanated mycolic acids in Mycobacterium tuberculosis. Identification and functional analysis of CMAS-2
K M George
Laboratory of Intracellular Parasites, NIAID, National Institutes of Health, Rocky Mountain Laboratories, Hamilton, Montana 59840, USA
J Biol Chem 270:27292-8. 1995
The major mycolic acid produced by Mycobacterium tuberculosis contains two cis-cyclopropanes in the meromycolate chain...
- In vivo efficacy in airway disease models of roflumilast, a novel orally active PDE4 inhibitor
D S Bundschuh
Department of Pharmacology, Byk Gulden, P O Box 10 03 10, 78403 Konstanz, Germany
J Pharmacol Exp Ther 297:280-90. 2001
..These results, coupled with the in vitro effects of roflumilast on inflammatory cells, suggest that roflumilast represents a potential new drug for the treatment of asthma and chronic obstructive pulmonary disease...
- Priming of group 2 metabotropic glutamate receptors facilitates induction of long-term depression in the dentate gyrus of freely moving rats
Leibniz Institute for Neurobiology, Department of Neurophysiology, Magdeburg, Germany
Neuropharmacology 37:1459-64. 1998
..The present study demonstrates that priming of group 2 mGluRs leads to induction of persistent LTD in the dentate gyrus in vivo, consistent with a role for group 2 mGluRs in metaplasticity...