pyridazines

Summary

Top Publications

  1. ncbi Glucose inhibition of glucagon secretion from rat alpha-cells is mediated by GABA released from neighboring beta-cells
    Anna Wendt
    Department of Physiological Sciences, Lund University, Lund, Sweden
    Diabetes 53:1038-45. 2004
  2. pmc Microscopic kinetics and energetics distinguish GABA(A) receptor agonists from antagonists
    M V Jones
    Department of Physiology, University of Wisconsin, Madison, Wisconsin 53706, USA
    Biophys J 81:2660-70. 2001
  3. ncbi Postconditioning with levosimendan reduces the infarct size involving the PI3K pathway and KATP-channel activation but is independent of PDE-III inhibition
    Antje Hönisch
    Department of Medicine and Cardiology, Heart Center Dresden University Hospital, University of Technology Dresden, Fetscherstr 74, 01307 Dresden, Germany
    Basic Res Cardiol 105:155-67. 2010
  4. doi Effects of rotenone and pyridaben on complex I electron transfer and on mitochondrial nitric oxide synthase functional activity
    Ana Navarro
    Department of Biochemistry and Molecular Biology, School of Medicine, University of Cadiz, Plaza Fragela 9, 11003 Cadiz, Spain
    J Bioenerg Biomembr 42:405-12. 2010
  5. pmc Ponatinib in refractory Philadelphia chromosome-positive leukemias
    Jorge E Cortes
    Division of Cancer Medicine, University of Texas M D Anderson Cancer Center, Houston, TX 77030, USA
    N Engl J Med 367:2075-88. 2012
  6. ncbi TPA023 [7-(1,1-dimethylethyl)-6-(2-ethyl-2H-1,2,4-triazol-3-ylmethoxy)-3-(2-fluorophenyl)-1,2,4-triazolo[4,3-b]pyridazine], an agonist selective for alpha2- and alpha3-containing GABAA receptors, is a nonsedating anxiolytic in rodents and primates
    John R Atack
    Neuroscience Research Centre, Merck Sharp and Dohme Research Laboratories, Terlings Park, Eastwick Road, Harlow, Essex CM20 2QR, UK
    J Pharmacol Exp Ther 316:410-22. 2006
  7. doi Subtype-selective GABA(A) receptor modulation yields a novel pharmacological profile: the design and development of TPA023
    John R Atack
    Department of Neuroscience, Johnson and Johnson Pharmaceutical Research and Development, Turnhoutseweg 30, Beerse B 2340, Belgium
    Adv Pharmacol 57:137-85. 2009
  8. ncbi Discovery of 3-[2-(imidazo[1,2-b]pyridazin-3-yl)ethynyl]-4-methyl-N-{4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl}benzamide (AP24534), a potent, orally active pan-inhibitor of breakpoint cluster region-abelson (BCR-ABL) kinase including th
    Wei Sheng Huang
    ARIAD Pharmaceuticals, Inc, 26 Landsdowne Street, Cambridge, Massachusetts 02139, USA
    J Med Chem 53:4701-19. 2010
  9. ncbi Ambrisentan for the treatment of pulmonary arterial hypertension: results of the ambrisentan in pulmonary arterial hypertension, randomized, double-blind, placebo-controlled, multicenter, efficacy (ARIES) study 1 and 2
    Nazzareno Galie
    Institute of Cardiology, University of Bologna, Via Massarenti, 9, 40138 Bologna, Italy
    Circulation 117:3010-9. 2008
  10. pmc A role for the RISK pathway and K(ATP) channels in pre- and post-conditioning induced by levosimendan in the isolated guinea pig heart
    E F Du Toit
    Department of Biomedical Sciences, Faculty of Health Sciences, University of Stellenbosch, Western Cape, South Africa
    Br J Pharmacol 154:41-50. 2008

Detail Information

Publications256 found, 100 shown here

  1. ncbi Glucose inhibition of glucagon secretion from rat alpha-cells is mediated by GABA released from neighboring beta-cells
    Anna Wendt
    Department of Physiological Sciences, Lund University, Lund, Sweden
    Diabetes 53:1038-45. 2004
    ..This effect was not observed in the presence of SR95531, and we therefore conclude that isradipine stimulates glucagon secretion by inhibition of GABA release...
  2. pmc Microscopic kinetics and energetics distinguish GABA(A) receptor agonists from antagonists
    M V Jones
    Department of Physiology, University of Wisconsin, Madison, Wisconsin 53706, USA
    Biophys J 81:2660-70. 2001
    ..Antagonist binding does not appear to produce such movements, and may in fact prevent them...
  3. ncbi Postconditioning with levosimendan reduces the infarct size involving the PI3K pathway and KATP-channel activation but is independent of PDE-III inhibition
    Antje Hönisch
    Department of Medicine and Cardiology, Heart Center Dresden University Hospital, University of Technology Dresden, Fetscherstr 74, 01307 Dresden, Germany
    Basic Res Cardiol 105:155-67. 2010
    ..Whether the reduction of mortality in cardiogenic shock by levosimendan may in part be based on this postconditioning effect remains to be elucidated in clinical setting...
  4. doi Effects of rotenone and pyridaben on complex I electron transfer and on mitochondrial nitric oxide synthase functional activity
    Ana Navarro
    Department of Biochemistry and Molecular Biology, School of Medicine, University of Cadiz, Plaza Fragela 9, 11003 Cadiz, Spain
    J Bioenerg Biomembr 42:405-12. 2010
    ..This fact is interpreted as an indication of mtNOS being structurally adjacent to complex I with an intermolecular mtNOS-complex I hydrophobic bonding that is stronger at high Δψ and weaker at low Δψ...
  5. pmc Ponatinib in refractory Philadelphia chromosome-positive leukemias
    Jorge E Cortes
    Division of Cancer Medicine, University of Texas M D Anderson Cancer Center, Houston, TX 77030, USA
    N Engl J Med 367:2075-88. 2012
    ..Ponatinib (AP24534) is a potent oral tyrosine kinase inhibitor that blocks native and mutated BCR-ABL, including the gatekeeper mutant T315I, which is uniformly resistant to tyrosine kinase inhibitors...
  6. ncbi TPA023 [7-(1,1-dimethylethyl)-6-(2-ethyl-2H-1,2,4-triazol-3-ylmethoxy)-3-(2-fluorophenyl)-1,2,4-triazolo[4,3-b]pyridazine], an agonist selective for alpha2- and alpha3-containing GABAA receptors, is a nonsedating anxiolytic in rodents and primates
    John R Atack
    Neuroscience Research Centre, Merck Sharp and Dohme Research Laboratories, Terlings Park, Eastwick Road, Harlow, Essex CM20 2QR, UK
    J Pharmacol Exp Ther 316:410-22. 2006
    ..In summary, the novel alpha2/alpha3-selective efficacy profile of TPA023 translates into a nonsedating anxiolytic profile that is distinct from nonselective agonists...
  7. doi Subtype-selective GABA(A) receptor modulation yields a novel pharmacological profile: the design and development of TPA023
    John R Atack
    Department of Neuroscience, Johnson and Johnson Pharmaceutical Research and Development, Turnhoutseweg 30, Beerse B 2340, Belgium
    Adv Pharmacol 57:137-85. 2009
    ..Collectively, these data demonstrate that the alpha2/alpha3-selective partial agonist efficacy of TPA023 translates into a novel pharmacological profile...
  8. ncbi Discovery of 3-[2-(imidazo[1,2-b]pyridazin-3-yl)ethynyl]-4-methyl-N-{4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl}benzamide (AP24534), a potent, orally active pan-inhibitor of breakpoint cluster region-abelson (BCR-ABL) kinase including th
    Wei Sheng Huang
    ARIAD Pharmaceuticals, Inc, 26 Landsdowne Street, Cambridge, Massachusetts 02139, USA
    J Med Chem 53:4701-19. 2010
    ..These data, coupled with a favorable ADME profile, support the potential of 20g to be an effective treatment for CML, including patients refractory to all currently approved therapies...
  9. ncbi Ambrisentan for the treatment of pulmonary arterial hypertension: results of the ambrisentan in pulmonary arterial hypertension, randomized, double-blind, placebo-controlled, multicenter, efficacy (ARIES) study 1 and 2
    Nazzareno Galie
    Institute of Cardiology, University of Bologna, Via Massarenti, 9, 40138 Bologna, Italy
    Circulation 117:3010-9. 2008
    ..Ambrisentan is a propanoic acid-based, A-selective endothelin receptor antagonist for the once-daily treatment of pulmonary arterial hypertension...
  10. pmc A role for the RISK pathway and K(ATP) channels in pre- and post-conditioning induced by levosimendan in the isolated guinea pig heart
    E F Du Toit
    Department of Biomedical Sciences, Faculty of Health Sciences, University of Stellenbosch, Western Cape, South Africa
    Br J Pharmacol 154:41-50. 2008
    ....
  11. ncbi Pharmacodynamic and pharmacokinetic effects of TPA023, a GABA(A) alpha(2,3) subtype-selective agonist, compared to lorazepam and placebo in healthy volunteers
    S L de Haas
    Centre for Human Drug Research, Leiden, The Netherlands
    J Psychopharmacol 21:374-83. 2007
    ..Contrary to lorazepam, TPA023 caused no detectable memory impairment or postural imbalance. These differences reflect the selectivity of TPA023 for different GABA(A) receptor subtypes...
  12. doi Inhibitors of PIM-1 kinase: a computational analysis of the binding free energies of a range of imidazo [1,2-b] pyridazines
    Slimane Doudou
    School of Chemistry, University of Manchester, Manchester, United Kingdom
    J Chem Inf Model 50:368-79. 2010
    ..The potential of mean force for the displacement of the glycine-rich phosphate binding loop (P-loop) has also been estimated and shown to be an important feature in the binding of these ligands...
  13. ncbi Levosimendan as a rescue drug in experimental propranolol-induced myocardial depression: a randomized study
    Heli Leppikangas
    Department of Anaesthesia, Tampere University Hospital, Tampere, Finland
    Ann Emerg Med 54:811-817.e1-3. 2009
    ..We hypothesize that levosimendan could reverse propranolol-induced severe negative inotropy in a porcine model of beta-blocker intoxication...
  14. pmc Postsynaptic mechanisms govern the differential excitation of cortical neurons by thalamic inputs
    Court Hull
    Neurobiology Section, Division of Biology, School of Medicine, University of California, San Diego, La Jolla, California 92093 0634, USA
    J Neurosci 29:9127-36. 2009
    ..Thus, thalamic afferent activity diverges into two routes that rely on unique complements of postsynaptic AMPARs and NMDARs to orchestrate the dynamic balance of excitation and inhibition as sensory input enters the cortex...
  15. pmc Inhibition of endothelin receptors in the treatment of pulmonary arterial hypertension: does selectivity matter?
    Christian F Opitz
    Department of Internal Medicine, DRK Kliniken Berlin, Köpenick, Berlin, Germany
    Eur Heart J 29:1936-48. 2008
    ..These characteristics bear more relation to the chemical or pharmacological properties of the drugs than to receptor selectivity itself...
  16. ncbi Endothelin antagonism prevents diabetic retinopathy in NOD mice: a potential role of the angiogenic factor adrenomedullin
    Sidney G Shaw
    Department of Clinical Experimental Research, University of Bern, Bern, CH 3010 Switzerland
    Exp Biol Med (Maywood) 231:1101-5. 2006
    ..ETRA antagonists may provide a novel therapeutic strategy to slow or prevent progression of retinal microvascular damage and proliferation in patients for whom there is clear evidence of activation of the ET-1 system...
  17. pmc Combination of V106I and V179D polymorphic mutations in human immunodeficiency virus type 1 reverse transcriptase confers resistance to efavirenz and nevirapine but not etravirine
    Hiroyuki Gatanaga
    AIDS Clinical Center, International Medical Center of Japan, 1 21 1 Toyama, Shinjuku ku, Tokyo 162 8655, Japan
    Antimicrob Agents Chemother 54:1596-602. 2010
    ..The combination of V106I and V179D is a newly identified NNRTI resistance pattern of mutations. The combination of polymorphic and minor resistance-associated mutations should be interpreted carefully...
  18. pmc Reducing abuse liability of GABAA/benzodiazepine ligands via selective partial agonist efficacy at alpha1 and alpha2/3 subtypes
    Nancy A Ator
    Division of Behavioral Biology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, Maryland, USA
    J Pharmacol Exp Ther 332:4-16. 2010
    ..In the context of other data, elimination of efficacy at the alpha(1) subtype of the GABA/benzodiazepine receptor is not sufficient to eliminate abuse liability but may do so when coupled with reduced alpha(2/3) subtype efficacy...
  19. ncbi The nuclear genes Lhcb and HEMA1 are differentially sensitive to plastid signals and suggest distinct roles for the GUN1 and GUN5 plastid-signalling pathways during de-etiolation
    Alex C McCormac
    School of Biological Sciences, University of Southampton, Bassett Crescent East, Southampton SO16 7PX, UK
    Plant J 40:672-85. 2004
    ..These results are consistent with plastid signals functioning in a feedback regulatory mechanism during chloroplast biogenesis, and suggest a key role for GUN1 during the early stages of chloroplast development...
  20. ncbi Levosimendan reduces mortality in critically ill patients. A meta-analysis of randomized controlled studies
    G Landoni
    Department of Anesthesiology and Intensive Care, Vita Salute San Raffaele University, Milan, Italy
    Minerva Anestesiol 76:276-86. 2010
    ..Levosimendan is a calcium sensitizer that is able to enhance myocardial contractility without increasing myocardial oxygen use. We conducted a meta-analysis to determine the impact of levosimendan on mortality in critically ill patients...
  21. doi Levosimendan facilitates weaning from cardiopulmonary bypass in patients undergoing coronary artery bypass grafting with impaired left ventricular function
    Heidi I Eriksson
    Department of Anesthesiology and Intensive Care, Helsinki University Central Hospital, Helsinki, Finland
    Ann Thorac Surg 87:448-54. 2009
    ..Levosimendan is a compound with vasodilatory and inotropic properties. Experimental data suggest effective reversal of stunning and cardioprotective properties...
  22. doi Structural mechanism of the Pan-BCR-ABL inhibitor ponatinib (AP24534): lessons for overcoming kinase inhibitor resistance
    Tianjun Zhou
    ARIAD Pharmaceuticals Inc, 26 Landsdowne Street, Cambridge, MA 02139, USA
    Chem Biol Drug Des 77:1-11. 2011
    ..The inhibitory mechanism exemplified by ponatinib may have broad relevance to designing inhibitors against other kinases with mutated gatekeeper residues...
  23. pmc The effects of levosimendan and glibenclamide on circulatory and metabolic variables in a canine model of acute hypoxia
    Lothar A Schwarte
    Department of Anaesthesiology, VU University Medical Center, Amsterdam, The Netherlands
    Intensive Care Med 37:701-10. 2011
    ....
  24. ncbi Selective modulation of tonic and phasic inhibitions in dentate gyrus granule cells
    Zoltan Nusser
    Department of Neurology, UCLA School of Medicine, Los Angeles, California 90095 1769, USA
    J Neurophysiol 87:2624-8. 2002
    ..Furthermore, we have identified distinct pharmacological tools to selectively modify tonic and phasic inhibitions, allowing future studies to investigate their specific roles in neuronal function...
  25. ncbi Bleaching herbicide norflurazon inhibits phytoene desaturase by competition with the cofactors
    J Breitenbach
    Botanisches Institut 213, , P.O. Box 111932, D-60054 Frankfurt, Germany
    J Agric Food Chem 49:5270-2. 2001
    ..6 mM and 0.23 microM, respectively. Inhibition of the phytoene desaturase from G. lutea by norflurazon was also competitive with respect to plastoquinone. The K(m) values of both enzymes for plastoquinone were very close...
  26. doi Monosynaptic and polysynaptic feed-forward inputs to mitral cells from olfactory sensory neurons
    Marion Najac
    Institut National de la Santé et de la Recherche Médicale Unité 603, Paris, France
    J Neurosci 31:8722-9. 2011
    ..These results confirm the existence of direct OSN to mitral cells synapses but also emphasize the prominence of intraglomerular feedforward pathways in the mitral cell response...
  27. pmc Neuroprotective properties of levosimendan in an in vitro model of traumatic brain injury
    Anna B Roehl
    Department of Anaesthesiology, RWTH Aachen University Hospital, Pauwelsstrase 30, 52074 Aachen, Germany
    BMC Neurol 10:97. 2010
    ..We investigated the neuroprotective properties of levosimendan, a novel inodilator, in an in vitro model of traumatic brain injury...
  28. ncbi Ambrisentan therapy in patients with pulmonary arterial hypertension who discontinued bosentan or sitaxsentan due to liver function test abnormalities
    Michael D McGoon
    Mayo Clinic, Rochester, MN 55905, USA
    Chest 135:122-9. 2009
    ..Because ambrisentan may provide benefits in PAH patients who have discontinued ERA therapy due to LFT abnormalities, we evaluated the safety and efficacy of ambrisentan in this patient population...
  29. ncbi Evidence-based use of levosimendan in different clinical settings
    Leonardo De Luca
    Division of Cardiology, European Hospital, Rome, Italy
    Eur Heart J 27:1908-20. 2006
    ..This review summarizes the evidence from published scientific literature regarding the use of levosimendan in various clinical settings...
  30. pmc Endogenous GABA and glutamate finely tune the bursting of olfactory bulb external tufted cells
    Abdallah Hayar
    Department of Neurobiology and Developmental Sciences, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, USA
    J Neurophysiol 98:1052-6. 2007
    ..We suggest that ET cell excitatory and inhibitory inputs may be encoded as a change in the pattern of spike bursting in ET cells, which together with mitral/tufted cells constitute the output circuit of the olfactory bulb...
  31. doi Synthesis and evaluation of pyrazolo[1,5-b]pyridazines as selective cyclin dependent kinase inhibitors
    Kirk L Stevens
    Department of Oncology, GlaxoSmithKline, Research Triangle Park, NC 27709, USA
    Bioorg Med Chem Lett 18:5758-62. 2008
    A novel series of pyrazolo[1,5-b]pyridazines have been synthesized and identified as cyclin dependant kinase inhibitors potentially useful for the treatment of solid tumors...
  32. pmc Potent activity of ponatinib (AP24534) in models of FLT3-driven acute myeloid leukemia and other hematologic malignancies
    Joseph M Gozgit
    ARIAD Pharmaceuticals, Inc, 26 Landsdowne Street, Cambridge, MA 02139, USA
    Mol Cancer Ther 10:1028-35. 2011
    ..Overall, these results support the investigation of ponatinib in patients with FLT3-ITD-driven AML and other hematologic malignancies driven by KIT, FGFR1, or PDGFRα...
  33. ncbi A double-blind, randomized, placebo-controlled study of pimobendan in dogs with dilated cardiomyopathy
    Virginia Luis Fuentes
    Department of Veterinary Clinical Studies, Royal Dick School of Veterinary Studies, Summerhall, Edinburgh, UK
    J Vet Intern Med 16:255-61. 2002
    ..4 (95% confidence interval 1.4-39.8). Pimobendan resulted in significant improvement in heart failure class when added to standard therapy in this group of dogs with DCM, and may have contributed to improved survival in DPs...
  34. doi Pharmacology of JNJ-37822681, a specific and fast-dissociating D2 antagonist for the treatment of schizophrenia
    Xavier Langlois
    Neuroscience, Janssen Research and Development, Janssen Pharmaceutica NV, Beerse, Belgium
    J Pharmacol Exp Ther 342:91-105. 2012
    ....
  35. doi Anti-ischemic effects of inotropic agents in experimental right ventricular infarction
    M Hein
    Department of Anesthesiology, University Hospital of Aachen, Aachen, Germany
    Acta Anaesthesiol Scand 53:941-8. 2009
    ..Therefore, we used a porcine model of RV ischemia and reperfusion (IR) injury to study the influence of milrinone, levosimendan and dobutamine on the extent and degree of myocardial injury...
  36. ncbi Levosimendan is a mitochondrial K(ATP) channel opener
    D M Kopustinskiene
    Institute for Biomedical Research, Kaunas University of Medicine, Kaunas, Lithuania
    Eur J Pharmacol 428:311-4. 2001
    ..Our results indicate that levosimendan opens mitochondrial K(ATP) channels...
  37. ncbi Mechanism of irregular firing of suprachiasmatic nucleus neurons in rat hypothalamic slices
    Nikolai I Kononenko
    Department of Biomedical Sciences, Colorado State University, Fort Collins, Colorado 80523, USA
    J Neurophysiol 91:267-73. 2004
    ..Thus GABAA receptor-mediated IPSPs appear responsible for irregular firing of SCN neurons in hypothalamic slices...
  38. ncbi Levosimendan effect on spinal cord ischemia-reperfusion injury following aortic clamping
    S Fehmi Katircioglu
    Cardiovascular Surgery Clinic, Turkiye Yuksek Ihtisas Hospital, Ankara, Turkey
    J Card Surg 23:44-8. 2008
    ..The aim of this experimental study was to investigate whether levosimendan has protective effects on spinal cord ischemia-reperfusion injury...
  39. ncbi Distinct functional and pharmacological properties of tonic and quantal inhibitory postsynaptic currents mediated by gamma-aminobutyric acid(A) receptors in hippocampal neurons
    D Bai
    Department of Physiology, University of Toronto, Toronto, Ontario, Canada
    Mol Pharmacol 59:814-24. 2001
    ..In summary, the receptors underlying the tonic current are functionally and pharmacologically distinct from quantally activated synaptic receptors and these receptors represent a novel target for neurodepressive drugs...
  40. doi Acute effects of levosimendan on cerebral and systemic perfusion and oxygenation in newborns: an observational study
    María Carmen Bravo
    Department of Neonatology, La Paz University Hospital, Madrid, Spain
    Neonatology 99:217-23. 2011
    ..Levosimendan, a novel inodilator agent, enhances myocardial contractility and causes peripheral and coronary vasodilation...
  41. ncbi An analysis of responses to levosimendan in the pulmonary vascular bed of the cat
    Bracken J De Witt
    Department of Anesthesiology, Texas Tech University Health Sciences Center, 3601 4th Street, Lubbock, TX 79430, USA
    Anesth Analg 94:1427-33, table of contents. 2002
    ....
  42. ncbi Endothelin receptor antagonists for pulmonary arterial hypertension: rationale and place in therapy
    Laura C Price
    Department of Cardiac Sciences, National Pulmonary Hypertension Service, Hammersmith Hospital, Imperial College Healthcare NHS Trust, London, UK
    Am J Cardiovasc Drugs 8:171-85. 2008
    ..Although their use as part of combination therapy with other agents is widespread, the evidence for this is not as robust, but appropriate investigation is underway...
  43. ncbi Pharmacological preconditioning by levosimendan is mediated by inducible nitric oxide synthase and mitochondrial KATP channel activation in the in vivo anesthetized rabbit heart model
    Biswadeep Das
    Department of Pharmacology, Sikkim Manipal Institute of Medical Sciences, 5th Mile, Tadong, Gangtok, Sikkim, India
    Vascul Pharmacol 47:248-56. 2007
    ..Levosimendan (LEV) is a new inodilator, whose mechanism of action includes calcium sensitization of contractile proteins and the opening of ATP-dependent potassium channels...
  44. ncbi Canine dilated cardiomyopathy: a retrospective study of prognostic findings in 367 clinical cases
    M W S Martin
    Veterinary Cardiorespiratory Centre, Thera House, Waverley Road, Kenilworth, UK
    J Small Anim Pract 51:428-36. 2010
    ..To review the association between clinical signs and diagnostic findings and the survival time of dogs with dilated cardiomyopathy (DCM), and any influence of treatment prescribed...
  45. ncbi Comparative cue generalization profiles of L-838, 417, SL651498, zolpidem, CL218,872, ocinaplon, bretazenil, zopiclone, and various benzodiazepines in chlordiazepoxide and zolpidem drug discrimination
    N R Mirza
    Department of In Vivo Pharmacology, Neurosearch A S, 93 Pederstrupvej, DK 2750 Ballerup, Denmark
    J Pharmacol Exp Ther 316:1291-9. 2006
    ....
  46. ncbi Beneficial effects of levosimendan on cerebral vasospasm induced by subarachnoid haemorrhage: an experimental study
    Sahika Liva Cengiz
    Neurosurgery Department, Selcuk University, Meram School of Medicine, Konya, Turkey
    Brain Inj 24:877-85. 2010
    ..The aim of this study was to investigate the ability of levosimendan to prevent cerebral vasospasm in a rabbit model of subarachnoid haemorrhage (SAH)...
  47. pmc Differences in spike train variability in rat vasopressin and oxytocin neurons and their relationship to synaptic activity
    Chunyan Li
    Department of Anatomy and Neurobiology, University of Tennessee Health Science Center, Memphis, TN 38163, USA
    J Physiol 581:221-40. 2007
    ..For example, the increased firing variability that precedes bursting in OT neurons during lactation could be related to significant changes in synaptic activity...
  48. doi Long-term efficacy and safety of raltegravir, etravirine, and darunavir/ritonavir in treatment-experienced patients: week 96 results from the ANRS 139 TRIO trial
    Catherine Fagard
    INSERM, ISPED, Centre INSERM U897 Epidemiologie Biostatistique, F 33000 Bordeaux, France
    J Acquir Immune Defic Syndr 59:489-93. 2012
    ..CD4 response was maintained (median change of +150 cells/mm(3)). No major toxicity was reported. This triple drug combination showed sustained efficacy and thus should be strongly considered for patients with multiclass-resistant virus...
  49. pmc Mechanistic characterization of GS-9190 (Tegobuvir), a novel nonnucleoside inhibitor of hepatitis C virus NS5B polymerase
    I Hung Shih
    Gilead Sciences, Inc, 333 Lakeside Dr, Foster City, CA 94404, USA
    Antimicrob Agents Chemother 55:4196-203. 2011
    ..Collectively, these data demonstrate that GS-9190 represents a novel class of nonnucleoside polymerase inhibitors that interact with NS5B likely through involvement of the β-hairpin in the thumb subdomain...
  50. ncbi Site dependent bioavailability and metabolism of levosimendan in dogs
    S Antila
    Orion Pharma, PO Box 65, 02101, Espoo, Finland
    Eur J Pharm Sci 9:85-91. 1999
    ..The bacteria or enzymes responsible for the metabolism of levosimendan are located in the lower parts of the gastrointestinal tract...
  51. doi Intracoronary levosimendan prevents myocardial ischemic damages and activates survival signaling through ATP-sensitive potassium channel and nitric oxide
    Philippe Primo Caimmi
    Department of Cardiac Surgery, Azienda Ospedaliera Universitaria Maggiore della Carità and University of East Piedmont A Avogadro, Corso Mazzini 18, 28100, Novara, Italy
    Eur J Cardiothorac Surg 39:e59-67. 2011
    ..In this study, we have examined the cardiac effects of different doses of intracoronary levosimendan on ischemia/reperfusion injuries, and the involvement of K(ATP) channels and nitric oxide (NO)...
  52. ncbi Effects of levosimendan on systemic and regional hemodynamics in septic myocardial depression
    Jacques Creteur
    Intensive Care Med 32:790; author reply 791-2. 2006
  53. doi Levosimendan for the treatment of acute severe heart failure: a meta-analysis of randomised controlled trials
    Anthony Delaney
    Intensive Care Unit, Royal North Shore Hospital, Pacific Highway, St Leonards, NSW, 2065, Australia
    Int J Cardiol 138:281-9. 2010
    ..The objective of this study was to critically review the literature to evaluate whether levosimendan compared to standard therapy, in patients with acute severe heart failure, is associated with improved clinical outcomes...
  54. ncbi An HPLC-PDA method for the simultaneous quantification of the HIV integrase inhibitor raltegravir, the new nonnucleoside reverse transcriptase inhibitor etravirine, and 11 other antiretroviral agents in the plasma of HIV-infected patients
    Antonio D'Avolio
    Department of Infectious Diseases, University of Torino, Amedeo di Savoia Hospital, Turin, Italy
    Ther Drug Monit 30:662-9. 2008
    ....
  55. ncbi Phase I dose escalation study of telatinib, a tyrosine kinase inhibitor of vascular endothelial growth factor receptor 2 and 3, platelet-derived growth factor receptor beta, and c-Kit, in patients with advanced or metastatic solid tumors
    Ferry A L M Eskens
    Department of Medical Oncology, Erasmus University Medical Center, PO Box 2040, Rotterdam, 3000 CA, The Netherlands
    J Clin Oncol 27:4169-76. 2009
    ..This phase I dose escalation study was conducted to evaluate the safety and tolerability of telatinib, with additional pharmacokinetic, pharmacodynamic, and efficacy assessments...
  56. ncbi Levosimendan in septic shock: another piece in the puzzle, but many pieces are still lacking
    Daniel De Backer
    Intensive Care Med 33:403-5. 2007
  57. ncbi Levosimendan improves hemodynamics and coronary flow reserve after percutaneous coronary intervention in patients with acute myocardial infarction and left ventricular dysfunction
    Leonardo De Luca
    Department of Cardiovascular and Respiratory Sciences, La Sapienza University, Rome, Italy
    Am Heart J 150:563-8. 2005
    ....
  58. ncbi Reducing the risk of major elective non-cardiac surgery: is there a role for levosimendan in the preoperative optimization of cardiac function?
    A Morelli
    Department of Anesthesiology and Intensive Care, University of Rome, La Sapienza, Rome, Italy
    Curr Drug Targets 10:863-71. 2009
    ..Nevertheless, large-scale trials are needed before final conclusions can be drawn on the use of levosimendan in this indication...
  59. ncbi Electrophysiologic effects of a calcium sensitizer inotrope levosimendan administered intravenously in patients with normal cardiac function
    L Toivonen
    Division of Cardiology, Helsinki University Central Hospital, Finland
    J Cardiovasc Pharmacol 35:664-9. 2000
    ..The effects on the ventricle were not substantial, and therefore the likelihood of provoking serious cardiac arrhythmias is not estimated to be high...
  60. ncbi 5-aryl-pyrazolo[3,4-b]pyridazines: potent inhibitors of glycogen synthase kinase-3 (GSK-3)
    Jason Witherington
    Department of Medicinal Chemistry, Neurology Centre of Excellence for Drug Discovery, GlaxoSmithKline Research Limited, New Frontiers Science Park, Third Avenue, Essex CM19 5AW, Harlow, UK
    Bioorg Med Chem Lett 13:1581-4. 2003
    ..Rationalisation of the binding mode suggested participation of a putative structural water molecule, which was subsequently confirmed by X-ray crystallography...
  61. pmc Pim kinase inhibitor, SGI-1776, induces apoptosis in chronic lymphocytic leukemia cells
    Lisa S Chen
    Department of Experimental Therapeutics, University of Texas M D Anderson Cancer Center, Houston, TX 77030, USA
    Blood 114:4150-7. 2009
    ..Consistent with a decline in new RNA synthesis, MCL-1 transcript levels were decreased after treatment with SGI-1776. These data suggest that SGI-1776 induces apoptosis in CLL and that the mechanism involves Mcl-1 reduction...
  62. ncbi Levosimendan restores both systolic and diastolic cardiac performance in lipopolysaccharide-treated rabbits: comparison with dobutamine and milrinone
    Damien Barraud
    Equipe d Accueil 322, Universite, Paris, France
    Crit Care Med 35:1376-82. 2007
    ..Our study aimed to fully characterize both systolic and diastolic abnormalities of sepsis-associated heart failure and to identify treatment that would support full-cycle cardiac improvement...
  63. doi Targeting the BCR-ABL signaling pathway in therapy-resistant Philadelphia chromosome-positive leukemia
    Thomas O'Hare
    Division of Hematology and Medical Oncology, Oregon Health and Science University Knight Cancer Institute, Portland, Oregon, USA
    Clin Cancer Res 17:212-21. 2011
    ....
  64. ncbi Differential effects of iontophoretic in vivo application of the GABA(A)-antagonists bicuculline and gabazine in sensory cortex
    Simone Kurt
    Leibniz Institute for Neurobiology, Brenneckestrasse 6, 39118 Magdeburg, Germany
    Hear Res 212:224-35. 2006
    ..The results have profound implications for microiontophoretic studies of the role of intracortical inhibition in sensory cortex...
  65. doi Inotropic agents improve the peripheral microcirculation of patients with end-stage chronic heart failure
    Serafim Nanas
    Pulmonary and Critical Care Medicine Department, Cardiopulmonary Exercise Testing and Rehabilitation Laboratory, Evgenidio Hospital, Athens, Greeece
    J Card Fail 14:400-6. 2008
    ..We evaluated the microcirculation by near-infrared spectroscopy (NIRS) occlusion technique before and after inotropic infusion...
  66. pmc The kinetics of inhibition of rat recombinant heteromeric alpha1beta glycine receptors by the low-affinity antagonist SR-95531
    Marco Beato
    Department of Pharmacology, University College London, Gower Street, London WC1E 6BT, UK
    J Physiol 580:171-9. 2007
    ..The fast unbinding rate of SR-95531 from the glycine receptor will make it useful for establishing the time course of glycine concentration at glycinergic synapses...
  67. doi Effects of levosimendan and dobutamine on experimental acute lung injury in rats
    Koray Erbuyun
    Department of Anesthesiology, Faculty of Medicine, Celal Bayar University, Manisa, Turkey
    Acta Histochem 111:404-14. 2009
    ..In this experimental sepsis model, treatment with levosimendan had a marked effect on attenuating or decreasing apoptosis and inflammation in the lung...
  68. doi Ambrisentan, an endothelin receptor type A-selective endothelin receptor antagonist, for the treatment of pulmonary arterial hypertension
    Martha Kingman
    University of Texas Southwestern Medical Center at Dallas, Heart and Lung Center, 5939 Harry Hines Blvd, Dallas, TX 75390, USA
    Expert Opin Pharmacother 10:1847-58. 2009
    ..Despite these data, the FDA requires monthly liver function tests monitoring. As with other ERAs, monthly pregnancy testing is required in all women of child bearing potential...
  69. doi Levosimendan but not norepinephrine improves microvascular oxygenation during experimental septic shock
    Michael Fries
    Department of Anesthesiology, University Hospital RWTH Aachen, Aachen, Germany
    Crit Care Med 36:1886-91. 2008
    ..To determine the effects of norepinephrine and levosimendan on microvascular perfusion and oxygenation in a rat model of septic shock...
  70. ncbi Tonically activated GABAA receptors in hippocampal neurons are high-affinity, low-conductance sensors for extracellular GABA
    Jacky Y T Yeung
    Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada
    Mol Pharmacol 63:2-8. 2003
    ..The receptors underlying tonic and phasic inhibitory conductances in hippocampal neurons are pharmacologically and biophysically distinct, suggesting that they serve different physiological roles...
  71. ncbi Levosimendan in patients with cardiogenic shock undergoing surgical revascularization: a case series
    Andreas Lehmann
    Department of Anesthesiology and Intensive Care Medicine, Municipal Hospital, Ludwigshafen, Germany
    Med Sci Monit 10:MT89-93. 2004
    ..These properties could be advantageous in patients with myocardial ischemia requiring inotropic support...
  72. pmc Levosimendan for resuscitating the microcirculation in patients with septic shock: a randomized controlled study
    Andrea Morelli
    Department of Anesthesiology and Intensive Care, University of Rome, La Sapienza, Viale del Policlinico 155, Rome 00161, Italy
    Crit Care 14:R232. 2010
    ..e. dobutamine). The primary end point was a difference of ≥ 20% in the microvascular flow index of small vessels (MFIs) among groups...
  73. ncbi Glia as a therapeutic target: selective suppression of human amyloid-beta-induced upregulation of brain proinflammatory cytokine production attenuates neurodegeneration
    Hantamalala Ralay Ranaivo
    Center for Drug Discovery and Chemical Biology, Chicago, Illinois 60611, USA
    J Neurosci 26:662-70. 2006
    ....
  74. pmc Resistance-associated mutations to etravirine (TMC-125) in antiretroviral-naïve patients infected with non-B HIV-1 subtypes
    Almoustapha Issiaka Maiga
    Laboratoire de Virologie, AP HP, Groupe Hospitalier Pitie Salpetriere, UPMC University Paris 06, INSERM U943, Paris, France
    Antimicrob Agents Chemother 54:728-33. 2010
    ..However, the transmission of drug-resistant viruses with Y181C in a non-B genetic background has a potential for impact on ETR susceptibility...
  75. ncbi Human amyloid beta-induced neuroinflammation is an early event in neurodegeneration
    Jeffrey M Craft
    Center for Drug Discovery and Chemical Biology, Northwestern University, Chicago, Illinois 60611, USA
    Glia 53:484-90. 2006
    ....
  76. pmc Factors associated with virological response to etravirine in nonnucleoside reverse transcriptase inhibitor-experienced HIV-1-infected patients
    Anne Genevieve Marcelin
    Department of Virology, Pitie Salpetriere Hospital, 83 Boulevard de l hopital, 75013 Paris, France
    Antimicrob Agents Chemother 54:72-7. 2010
    ..In conclusion, ETR was associated with high response rates in NNRTI-experienced patients in combination with other active drugs regardless of the therapeutic class used...
  77. pmc Development of a novel therapeutic suppressor of brain proinflammatory cytokine up-regulation that attenuates synaptic dysfunction and behavioral deficits
    Wenhui Hu
    Center for Drug Discovery and Chemical Biology, Northwestern University, 303 E Chicago Avenue, Mail Code W896, Chicago, IL 60611, USA
    Bioorg Med Chem Lett 17:414-8. 2007
    ..The development and large-scale availability of this novel compound allow exploration of new, potentially disease-modifying, therapeutic approaches to CNS disorders...
  78. doi Levosimendan pre-treatment improves outcomes in patients undergoing coronary artery bypass graft surgery
    L Tritapepe
    Department of Anesthesiology and Intensive Care, Sapienza University of Rome, Rome, Italy
    Br J Anaesth 102:198-204. 2009
    ..We thus decided to investigate whether pharmacological pre-treatment with levosimendan reduces intensive care unit (ICU) length of stay in patients undergoing elective myocardial revascularization under cardiopulmonary bypass...
  79. ncbi Efficacy and safety of perioperative infusion of levosimendan in patients with compromised cardiac function undergoing open-heart surgery: importance of early use
    Androniki Tasouli
    ICU, Onassis Cardiac Surgery Center, Marathonamahon 18, 14572 Athens, Greece
    Eur J Cardiothorac Surg 32:629-33. 2007
    ..Levosimendan is a promising new inotrope. We investigate the proper time for its infusion during or after open-heart surgery to avoid complications related with low-output syndrome and high dosage of inotropes...
  80. pmc TMC278, a next-generation nonnucleoside reverse transcriptase inhibitor (NNRTI), active against wild-type and NNRTI-resistant HIV-1
    Hilde Azijn
    Tibotec Virco BVBA, Generaal De Wittelaan L11 B3, B 2800 Mechelen, Belgium
    Antimicrob Agents Chemother 54:718-27. 2010
    ..E138R was identified as a new NNRTI RAM. These in vitro analyses demonstrate that TMC278 is a potent next-generation NNRTI, with a high genetic barrier to resistance development...
  81. ncbi Early and sustained haemodynamic improvement with levosimendan compared to intraaortic balloon counterpulsation (IABP) in cardiogenic shock complicating acute myocardial infarction
    Arnd Christoph
    Department of Medicine III, Martin Luther University Halle Wittenberg, Germany
    Acute Card Care 10:49-57. 2008
    ..To investigate the haemodynamic effects of levosimendan in patients with cardiogenic shock (CS) complicating acute myocardial infarction in comparison to the effects of intra-aortic balloon counterpulsation (IABP)...
  82. ncbi The cardioprotective effects of levosimendan: preclinical and clinical evidence
    Piero Pollesello
    Orion Pharma, Cardiology and Critical Care, Espoo, Finland
    J Cardiovasc Pharmacol 50:257-63. 2007
    ..A therapeutic approach to acute heart failure that includes a cardioprotective strategy could have a clinically meaningful benefit on disease progression beyond alleviation of symptoms...
  83. ncbi Is there a place for levosimendan in the intensive care unit?
    Anthony Delaney
    Northern Clinical School, Faculty of Medicine, University of Sydney, Sydney, NSW, Australia
    Crit Care Resusc 9:290-2. 2007
    ..However, before concluding that there is a place for routine use of levosimendan in the intensive care unit, a careful appraisal of all available evidence is needed...
  84. doi Overview of emerging pharmacologic agents for acute heart failure syndromes
    Leonardo De Luca
    Department of Cardiovascular Sciences, European Hospital, Rome, Italy
    Eur J Heart Fail 10:201-13. 2008
    ..There is, therefore, an unmet need for new pharmacologic agents for the early management of AHFS that may improve both short- and long-term outcomes...
  85. ncbi Levosimendan improves the initial outcome of cardiopulmonary resuscitation in a swine model of cardiac arrest
    E Koudouna
    Department of Experimental Surgery and Surgical Research, Medical School, University of Athens, 15B Agiou Thoma Street, 11527 Athens, Greece
    Acta Anaesthesiol Scand 51:1123-9. 2007
    ..The aim of this study was to assess whether a calcium sensitizer agent, such as levosimendan, administered in combination with epinephrine during cardiopulmonary resuscitation, would improve the initial resuscitation success...
  86. ncbi Role of levosimendan in sepsis and septic shock
    Bernardo Bollen Pinto
    Department of Anesthesiology and Intensive Care, University Hospital of Muenster, Muenster, Germany
    Curr Opin Anaesthesiol 21:168-77. 2008
    ..To present the pharmacologic and biologic profile of levosimendan and discuss potential indications in the treatment of sepsis and septic shock, with a special focus on myocardial and pulmonary dysfunction...
  87. ncbi Levosimendan vs dobutamine for patients with acute decompensated heart failure: the SURVIVE Randomized Trial
    Alexandre Mebazaa
    Department of Anesthesiology, Université Paris Diderot and Hospital Lariboisière AP HP, Paris, France
    JAMA 297:1883-91. 2007
    ..Because acute decompensated heart failure causes substantial morbidity and mortality, there is a need for agents that at least improve hemodynamics and relieve symptoms without adversely affecting survival...
  88. doi Preclinical characterization of A-582941: a novel alpha7 neuronal nicotinic receptor agonist with broad spectrum cognition-enhancing properties
    Karin R Tietje
    Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, Illinois 60064, USA
    CNS Neurosci Ther 14:65-82. 2008
    ....
  89. ncbi Signals from chloroplasts converge to regulate nuclear gene expression
    Shai Koussevitzky
    Howard Hughes Medical Institute, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA
    Science 316:715-9. 2007
    ..We propose a model in which multiple indicators of aberrant plastid function in Arabidopsis are integrated upstream of GUN1 within plastids, which leads to ABI4-mediated repression of nuclear-encoded genes...
  90. doi Pharmacokinetics of intravenous levosimendan and its metabolites in subjects with hepatic impairment
    Jaakko Puttonen
    Orion Pharma, Clinical R and D, Kuopio, Finland
    J Clin Pharmacol 48:445-54. 2008
    ..However, because the maximum duration of levosimendan infusion is 24 hours, dosing adjustments of levosimendan may not be required in subjects with impaired hepatic function...
  91. ncbi Levosimendan: from basic science to clinical practice
    John T Parissis
    Heart Failure Clinic and Second Cardiology Department, Attikon University Hospital, Maroussi, Athens, Greece
    Heart Fail Rev 14:265-75. 2009
    ....
  92. ncbi Effects of levosimendan and dobutamine in experimental acute endotoxemia: a preliminary controlled study
    Arnaldo Dubin
    Catedra de Farmacologia, Facultad de Ciencias Medicas, Universidad Nacional de La Plata, 42 No 577, 1900, La Plata, Argentina
    Intensive Care Med 33:485-94. 2007
    ..To test the hypothesis that levosimendan increases systemic and intestinal oxygen delivery (DO(2)) and prevents intramucosal acidosis in septic shock...
  93. ncbi Duration of the beneficial effects of levosimendan in decompensated heart failure as measured by echocardiographic indices and B-type natriuretic peptide
    Anthony S McLean
    Department of Intensive Care Medicine, University of Sydney, Nepean Hospital, Penrith, New South Wales 2750, Australia
    J Cardiovasc Pharmacol 46:830-5. 2005
    ..In conclusion, LS transiently improved the cardiac function, and the effects lasted for at least 7 days after discontinuation of infusion. Most effects, except LVEF, were not significantly different from baseline on day 30...
  94. ncbi Hemodynamic and neurohumoral effects of continuous infusion of levosimendan in patients with congestive heart failure
    M S Nieminen
    Helsinki University, Finland
    J Am Coll Cardiol 36:1903-12. 2000
    ..We sought to define the therapeutic dose range of levosimendan in patients with New York Heart Association class II-IV heart failure of ischemic origin...
  95. ncbi Pyridazines. Part 31: synthesis and antiplatelet activity of 4,5-disubstituted-6-phenyl-3(2H)-pyridazinones
    Eddy Sotelo
    Departamento de Quimica Organica, Laboratorio de Quimica Farmaceutica, Esapaña
    Chem Pharm Bull (Tokyo) 50:1574-7. 2002
    ..Some of these compounds show a dose-dependent activity and were found to be more active than their 5-substituted analogues...
  96. ncbi Levosimendan improves diastolic and systolic function in failing human myocardium
    P M Janssen
    Abt Kardiologie und Pneumologie, Universitat Gottingen, Gottingen, Germany
    Eur J Pharmacol 404:191-9. 2000
    ..Levosimendan improves both systolic and diastolic function in failing human myocardium. Effects are even more pronounced at higher heart rates and under prevailing diastolic dysfunction...
  97. ncbi Influence of the novel inotropic agent levosimendan on isometric tension and calcium cycling in failing human myocardium
    G Hasenfuss
    Zentrum Innere Medizin, Abteilung für Kardiologie und Pneumologie, Universitat Gottingen, Germany
    Circulation 98:2141-7. 1998
    ..Levosimendan was shown to increase calcium sensitivity by a novel mechanism and to inhibit phosphodiesterase III activity in animal myocardium...
  98. ncbi The contractile apparatus as a target for drugs against heart failure: interaction of levosimendan, a calcium sensitiser, with cardiac troponin c
    Tia Sorsa
    Orion Pharma, Cardiovascular Research, Espoo, Finland
    Mol Cell Biochem 266:87-107. 2004
    ..Finally, the binding of levosimendan to cTnC and its mechanism of action are described and the results discussed under the light of the action of this drug in vitro and in vivo...
  99. ncbi Vasodilating mechanisms of levosimendan
    Hisashi Yokoshiki
    Cardiovasc Drugs Ther 17:111-3. 2003
  100. ncbi Levosimendan is superior to milrinone and dobutamine in selectively increasing microvascular gastric mucosal oxygenation in dogs
    Lothar A Schwarte
    Department of Anesthesiology, University Hospital of Dusseldorf, Germany
    Crit Care Med 33:135-42; discussion 246-7. 2005
    ..We compared systemic and regional effects of levosimendan with those of established inotropes, milrinone and dobutamine...
  101. ncbi The novel calcium sensitizer levosimendan activates the ATP-sensitive K+ channel in rat ventricular cells
    H Yokoshiki
    Department of Molecular and Cellular Physiology, College of Medicine, University of Cincinnati, Ohio 45267 0576, USA
    J Pharmacol Exp Ther 283:375-83. 1997
    ....

Research Grants120 found, 100 shown here

  1. Integrative Chemical Biology of Neurodegeneration: Foundation to Novel Therapies
    D Watterson; Fiscal Year: 2008
    ..PUBLIC HEALTH RELEVANCE: Successful completion of the proposed studies will provide a foundation for immediate translation of basic science into potential disease-modifying clinical interventions using new classes of therapeutics. ..
  2. Development of a Novel Anti-Neuroinflammatory AD Therapeutic
    D Watterson; Fiscal Year: 2007
    ..This U01 project has highly feasible annual milestones, with the final one being development of a synthetic protocol compatible with GMP synthesis by an FDA compliant contract research organization. [unreadable] [unreadable] [unreadable]..
  3. Development of Novel p38 MAPK Inhibitors as Therapeutics for CNS Disorders
    D Watterson; Fiscal Year: 2008
    ..PUBLIC HEALTH RELEVANCE Successful completion of the proposed investigations will provide novel, efficacious compounds required for clinical development of new therapies for neurological disorders. ..
  4. Development of a Novel Anti-Neuroinflammatory AD Therapeutic
    D Watterson; Fiscal Year: 2008
    ..This U01 project has highly feasible annual milestones, with the final one being development of a synthetic protocol compatible with GMP synthesis by an FDA compliant contract research organization. [unreadable] [unreadable] [unreadable]..
  5. Development of a Novel Anti-Neuroinflammatory AD Therapeutic
    D Watterson; Fiscal Year: 2008
    ..This U01 project has highly feasible annual milestones, with the final one being development of a synthetic protocol compatible with GMP synthesis by an FDA compliant contract research organization. ..
  6. Functional analysis of retinal inhibitory processes
    Jozsef Vigh; Fiscal Year: 2009
    ..The proposed research investigates the natural mechanisms underlying contour detection. The results can be used to guide the design of prosthetic vision devices to restore some sight to blind people. ..
  7. TNF-ALPHA REGULATION OF AT1 RECEPTOR & POST-MI FIBROSIS
    Barry Greenberg; Fiscal Year: 2001
    ..This information will provide important insights into the pathogenesis of post-MI fibrosis. ..
  8. Acute Renal Failure: Mechanisms and Adaptive Responses
    RICHARD ZAGER; Fiscal Year: 2007
    ....
  9. Chemogenomics to Identify New Molecular Targets in PF
    William Henderson; Fiscal Year: 2005
    ..These studies represent a focused effort using chemogenomics to identify, develop, and validate small molecule inhibitors of AP-1/TGFBeta-driven profibrotic gene expression as novel therapies in PF patients. ..
  10. SLEEP/WAKE-RELATED NEURONAL ACTIVITY IN THE MOUSE
    Gerald Marks; Fiscal Year: 2001
    ..A valuable byproduct of this work will assist in providing rational interventions in disease states such as epilepsy when there is a failure of these mechanisms. ..
  11. TNF-ALPHA REGULATION OF AT1 RECEPTOR & POST-MI FIBROSIS
    Barry Greenberg; Fiscal Year: 2001
    ..This information will provide important insights into the pathogenesis of post-MI fibrosis. ..
  12. ACUTE RENAL FAILURE--IMPACT OF FLUORINATED ANESTHETICS
    RICHARD ZAGER; Fiscal Year: 2001
    ....
  13. 5-LIPOXYGENASE PRODUCTS IN ASTHMATIC IMMUNE RESPONSE
    William Henderson; Fiscal Year: 2001
    ....
  14. THE ROLE OF EPSILON SUBUNIT IN GABAA RECEPTOR FUNCTION
    TIM HALES; Fiscal Year: 2001
    ..Human homomeric and heteromeric 5-HT3 receptors are modulated by the intravenous anesthetic propofol which is reported to have anti-emetic properties. ..
  15. Natriuretic Peptides in Pulmonary Endothelial Cell Barrier Function
    James Klinger; Fiscal Year: 2008
    ..Findings from these studies will further our understanding of cellular mechanism that modulate pulmonary edema formation and determine if the NPs and their receptors are potential therapeutic targets for acute lung injury. ..
  16. Iron Therapy in Renal Disease: Potential Toxicities
    RICHARD ZAGER; Fiscal Year: 2008
    ..Potential reasons for these differences will be assessed, with the ultimate goal of defining the safest way of administering parenteral irons to renal disease patients. ..
  17. THE ROLE OF EPSILON SUBUNIT IN GABAA RECEPTOR FUNCTION
    TIM HALES; Fiscal Year: 2002
    ..Human homomeric and heteromeric 5-HT3 receptors are modulated by the intravenous anesthetic propofol which is reported to have anti-emetic properties. ..
  18. ORAL TOLERANCE IN PLP INDUCED EAE--MOLECULAR MECHANISMS
    William Karpus; Fiscal Year: 2002
    ..These studies should lead to a better understanding of the immunoregulatory mechanisms of oral tolerance which could potentially be used to control pathologic T cell-mediated immune responses. ..
  19. Functional Analysis of GABAerglc Sedative/Anxiolytics
    NANCY ATOR; Fiscal Year: 2005
    ..abstract_text> ..
  20. Altered Function of a GABA-A receptor epilepsy mutation
    Mathew Jones; Fiscal Year: 2005
    ..abstract_text> ..
  21. Clozapine Treatment of Schizophrenic Patients
    Robert Buchanan; Fiscal Year: 2005
    ..The study will provide new information on the clinical utility of adjunctive risperidone in treatment-resistant patients who fail to adequately respond to clozapine. ..
  22. Chemogenomics to Identify New Molecular Targets in PF
    William Henderson; Fiscal Year: 2004
    ..These studies represent a focused effort using chemogenomics to identify, develop, and validate small molecule inhibitors of AP-1/TGFBeta-driven profibrotic gene expression as novel therapies in PF patients. ..
  23. Clozapine Treatment of Schizophrenic Patients
    Robert Buchanan; Fiscal Year: 2003
    ..The study will provide new information on the clinical utility of adjunctive risperidone in treatment-resistant patients who fail to adequately respond to clozapine. ..
  24. 5-LIPOXYGENASE PRODUCTS IN ASTHMATIC IMMUNE RESPONSE
    William Henderson; Fiscal Year: 2004
    ..abstract_text> ..
  25. Altered Function of a GABA-A receptor epilepsy mutation
    Mathew Jones; Fiscal Year: 2004
    ..abstract_text> ..
  26. Functional Analysis of GABAerglc Sedative/Anxiolytics
    NANCY ATOR; Fiscal Year: 2006
    ..abstract_text> ..
  27. Chemogenomics to Identify New Molecular Targets in PF
    William Henderson; Fiscal Year: 2006
    ..These studies represent a focused effort using chemogenomics to identify, develop, and validate small molecule inhibitors of AP-1/TGFBeta-driven profibrotic gene expression as novel therapies in PF patients. ..
  28. The Role of Epsilon Subunit in GABA Receptor Function
    TIM HALES; Fiscal Year: 2007
    ..A better understanding of GABAA receptors and their potential for adaptation will help increase our understanding of changes in neuronal inhibition during epilepsy. ..
  29. Effect of Daily Exercise on Cardiac Autonomic Regulation
    GEORGE BILLMAN; Fiscal Year: 2003
    ..Ventricular contractile responses to Beta1- and Beta2-adrenoceptor stimulation will be examined in vivo by echocardiography and in vitro by single cell fluorescence microscopy/video edge detection. ..
  30. Altered Function of a GABA-A receptor epilepsy mutation
    Mathew Jones; Fiscal Year: 2007
    ..abstract_text> ..
  31. THE ROLE OF CHEMOKINES IN AUTOIMMUNE ENCEPHALOMYELITIS
    William Karpus; Fiscal Year: 2007
    ..These studies will help to understand the immunopathogenesis of MS and provide a basis for the development of novel chemokine and chemokine receptor therapies for treatment of ongoing disease. ..
  32. ANXIOLYTIC EFFECTS AND ABUSE OF BZ RECEPTOR LIGANDS
    JAMES ROWLETT; Fiscal Year: 2002
    ....
  33. 5-LIPOXYGENASE PRODUCTS IN ASTHMATIC IMMUNE RESPONSE
    William Henderson; Fiscal Year: 2002
    ....
  34. TNF-ALPHA REGULATION OF AT1 RECEPTOR & POST-MI FIBROSIS
    Barry Greenberg; Fiscal Year: 2000
    ..This information will provide important insights into the pathogenesis of post-MI fibrosis. ..
  35. THE ROLE OF CHEMOKINES IN AUTOIMMUNE ENCEPHALOMYELITIS
    William Karpus; Fiscal Year: 2000
    ..abstract_text> ..
  36. BLOOD PRESSURE CONTROL BY FOREBRAIN & BRAINSTEM NEURONS
    SUSAN BARMAN; Fiscal Year: 1990
    ..The electrophysiological techniques to be used include spike-triggered averaging of SND, antidromic mapping and tests for axonal branching, and unit minus or greater than unit crosscorrelation analysis...
  37. The reinforcing and discriminative stimulus effects of orally administered MDMA
    NANCY ATOR; Fiscal Year: 2009
    ..Our proposal will generate data fundamental to the future development of pharmacotherapies for MDMA abuse, thereby contributing to our long-term goal of facilitating treatment of MDMA intoxication, overdose, and use/abuse. ..
  38. The reinforcing and discriminative stimulus effects of orally administered MDMA
    Nancy A Ator; Fiscal Year: 2010
    ..Our proposal will generate data fundamental to the future development of pharmacotherapies for MDMA abuse, thereby contributing to our long-term goal of facilitating treatment of MDMA intoxication, overdose, and use/abuse. ..
  39. ANXIOLYTIC EFFECTS AND ABUSE OF BZ RECEPTOR LIGANDS
    JAMES ROWLETT; Fiscal Year: 2009
    ..The aim of this revision to our parent grant is to uncover sex differences in the abuse potential of benzodiazepines, with the overall goal of developing safer drugs for treating anxiety and sleep disorders regardless of gender. ..
  40. Natriuretic Peptides in Pulmonary Endothelial Cell Barrier Function
    James Klinger; Fiscal Year: 2009
    ..Findings from these studies will further our understanding of cellular mechanism that modulate pulmonary edema formation and determine if the NPs and their receptors are potential therapeutic targets for acute lung injury. ..
  41. GABA-A alpha5 cognitive enhancers: pharmacology and neuropsychology in macaques
    Nancy A Ator; Fiscal Year: 2010
    ....
  42. 5-LIPOXYGENASE PRODUCTS IN ASTHMATIC IMMUNE RESPONSE
    William Henderson; Fiscal Year: 1999
    ....
  43. HIV, Inflammation, and Endothelial Dysfunction
    Samir Gupta; Fiscal Year: 2008
    ..End of Abstract) ..
  44. SLEEP/WAKE-RELATED NEURONAL ACTIVITY
    Gerald Marks; Fiscal Year: 1999
    ..A valuable byproduct of this work will assist in providing rational interventions in disease states such as epilepsy when there is a failure of these mechanisms. ..
  45. THE ROLE OF CHEMOKINES IN AUTOIMMUNE ENCEPHALOMYELITIS
    William Karpus; Fiscal Year: 1999
    ..abstract_text> ..
  46. ANALYSIS OF ANXIOLYTICS AS DISCRIMINATIVE STIMULI
    NANCY ATOR; Fiscal Year: 1993
    ....
  47. BLOOD PRESSURE CONTROL BY FOREBRAIN & BRAINSTEM NEURONS
    SUSAN BARMAN; Fiscal Year: 2008
    ..unreadable] [unreadable]..
  48. ACISIR: Enhancing Recovery of People with Schizophrenia
    Robert Buchanan; Fiscal Year: 2008
    ..Operations Core ..
  49. ANXIOLYTIC EFFECTS AND ABUSE OF BZ RECEPTOR LIGANDS
    JAMES ROWLETT; Fiscal Year: 2000
    ....
  50. Novel GABA-A Modulators as Cognitive Enhancers
    James K Rowlett; Fiscal Year: 2010
    ..Because these compounds appear to be remarkably safe, they may provide a promising new approach for treating memory decline associated with Alzheimer's and other related disorders. ..
  51. Nonhuman Primate Model of Benzodiazepine Relapse
    JAMES ROWLETT; Fiscal Year: 2002
    ....
  52. Genes Underlying the Response to Inhaled Anesthetics
    James Sonner; Fiscal Year: 2008
    ....
  53. GABA-A alpha5 cognitive enhancers: pharmacology and neuropsychology in macaques
    NANCY ATOR; Fiscal Year: 2009
    ....
  54. Primate Model of the Transition to Cocaine Addiction
    JAMES ROWLETT; Fiscal Year: 2005
    ..The results will provide needed information for developing a nonhuman primate model that can serve as a quantitative platform for future research on neuroadaptations underlying the transition to persistent cocaine self-administration. ..
  55. The Mas Receptor is Required for Angiotensin-(1-7) Effects in Cardiac Remodeling
    Barry Greenberg; Fiscal Year: 2009
    ....
  56. ANALYSIS OF ANXIOLYTICS AS DISCRIMINATIVE STIMULI
    NANCY ATOR; Fiscal Year: 1991
    ....
  57. Progestins non-genomic actions for socio-sexual behavior
    Cheryl Frye; Fiscal Year: 2005
    ..abstract_text> ..
  58. BRAINSTEM MECHANISMS OF REM SLEEP
    Gerald Marks; Fiscal Year: 2006
    ..Information concerning these control mechanisms are essential to understanding the physiological processes manifested during both normal and pathological sleep/wake states. ..
  59. THE ROLE OF CHEMOKINES IN AUTOIMMUNE ENCEPHALOMYELITIS
    William Karpus; Fiscal Year: 2008
    ..These studies will help to understand the immunopathogenesis of MS and provide a basis for the development of novel chemokine and chemokine receptor therapies for treatment of ongoing disease. ..
  60. GABA-A alpha5 cognitive enhancers: pharmacology and neuropsychology in macaques
    NANCY ATOR; Fiscal Year: 2008
    ....
  61. THE ROLE OF CHEMOKINES IN AUTOIMMUNE ENCEPHALOMYELITIS
    William Karpus; Fiscal Year: 2006
    ..These studies will help to understand the immunopathogenesis of MS and provide a basis for the development of novel chemokine and chemokine receptor therapies for treatment of ongoing disease. ..
  62. The reinforcing and discriminative stimulus effects of orally administered MDMA
    NANCY ATOR; Fiscal Year: 2008
    ..Our proposal will generate data fundamental to the future development of pharmacotherapies for MDMA abuse, thereby contributing to our long-term goal of facilitating treatment of MDMA intoxication, overdose, and use/abuse. ..
  63. The FIOCRUZ Therapeutic and Prevention HIV/AIDS Clinical Trials Unit (FioTrials)
    Beatriz Grinsztejn; Fiscal Year: 2008
    ..administrative component: ..
  64. Brainstem Mechanisms of Rapid Eye Movement Sleep
    Gerald Marks; Fiscal Year: 2007
    ..Information concerning these control mechanisms are essential to understanding the physiological processes manifested during both normal and pathological sleep/wake states. ..
  65. THE ROLE OF CHEMOKINES IN AUTOIMMUNE ENCEPHALOMYELITIS
    William Karpus; Fiscal Year: 2009
    ..These studies will help to understand the immunopathogenesis of MS and provide a basis for the development of novel chemokine and chemokine receptor therapies for treatment of ongoing disease. ..
  66. Functional Analysis of GABAerglc Sedative/Anxiolytics
    NANCY ATOR; Fiscal Year: 2007
    ..abstract_text> ..
  67. THE ROLE OF CHEMOKINES IN AUTOIMMUNE ENCEPHALOMYELITIS
    William Karpus; Fiscal Year: 2005
    ..These studies will help to understand the immunopathogenesis of MS and provide a basis for the development of novel chemokine and chemokine receptor therapies for treatment of ongoing disease. ..
  68. ORAL TOLERANCE IN PLP INDUCED EAE--MOLECULAR MECHANISMS
    William Karpus; Fiscal Year: 2000
    ..These studies should lead to a better understanding of the immunoregulatory mechanisms of oral tolerance which could potentially be used to control pathologic T cell-mediated immune responses. ..
  69. BRAINSTEM MECHANISMS OF REM SLEEP
    Gerald Marks; Fiscal Year: 2000
    ..Preliminary data strongly indicate that cAMP has this role in the PRF. This project will begin to elucidate the mechanisms of the long-term control of REM sleep. ..
  70. ANALYSIS OF ANXIOLYTICS AS DISCRIMINATIVE STIMULI
    NANCY ATOR; Fiscal Year: 1990
    ....
  71. ANALYSIS OF ANXIOLYTICS AS DISCRIMINATIVE STIMULI
    NANCY ATOR; Fiscal Year: 1992
    ....
  72. FUNCTIONAL ANALYSIS OF GABAERGIC SEDATIVE/ANXIOLYTICS
    NANCY ATOR; Fiscal Year: 1999
    ..This research should inform current thinking over the ways in which stimulus control processes operate in determining chronic drug-taking. ..
  73. ORAL TOLERANCE IN PLP INDUCED EAE--MOLECULAR MECHANISMS
    William Karpus; Fiscal Year: 1999
    ..These studies should lead to a better understanding of the immunoregulatory mechanisms of oral tolerance which could potentially be used to control pathologic T cell-mediated immune responses. ..
  74. BRAINSTEM MECHANISMS OF REM SLEEP
    Gerald Marks; Fiscal Year: 1999
    ..Preliminary data strongly indicate that cAMP has this role in the PRF. This project will begin to elucidate the mechanisms of the long-term control of REM sleep. ..
  75. FUNCTIONAL ANALYSIS OF GABAERGIC SEDATIVE/ANXIOLYTICS
    NANCY ATOR; Fiscal Year: 2000
    ..This research should inform current thinking over the ways in which stimulus control processes operate in determining chronic drug-taking. ..
  76. SLEEP/WAKE-RELATED NEURONAL ACTIVITY IN THE MOUSE
    Gerald Marks; Fiscal Year: 2000
    ..A valuable byproduct of this work will assist in providing rational interventions in disease states such as epilepsy when there is a failure of these mechanisms. ..
  77. BRAINSTEM MECHANISMS OF REM SLEEP
    Gerald Marks; Fiscal Year: 2005
    ..Information concerning these control mechanisms are essential to understanding the physiological processes manifested during both normal and pathological sleep/wake states. ..