pyridazines

Summary

Top Publications

  1. pmc AP24534, a pan-BCR-ABL inhibitor for chronic myeloid leukemia, potently inhibits the T315I mutant and overcomes mutation-based resistance
    Thomas O'Hare
    Division of Hematology and Medical Oncology, Oregon Health and Science University Knight Cancer Institute, Portland, OR 97239, USA
    Cancer Cell 16:401-12. 2009
  2. 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
  3. ncbi 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
  4. ncbi Levosimendan protection against kidney ischemia/reperfusion injuries in anesthetized pigs
    Elena Grossini
    Department of Translational Medicine, University East Piedmont, Via Solaroli 17, I 28100 Novara, Italy
    J Pharmacol Exp Ther 342:376-88. 2012
  5. 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
  6. ncbi Levosimendan preserves the contractile responsiveness of hypoxic human myocardium via mitochondrial K(ATP) channel and potential pERK 1/2 activation
    Paul F Soeding
    Cardiovascular Therapeutics Unit, Department of Pharmacology, University of Melbourne, Parkville, Australia
    Eur J Pharmacol 655:59-66. 2011
  7. pmc Substituted imidazopyridazines are potent and selective inhibitors of Plasmodium falciparum calcium-dependent protein kinase 1 (PfCDPK1)
    Timothy M Chapman
    Centre for Therapeutics Discovery, MRC Technology, Mill Hill, London NW7 1AD, UK
    Bioorg Med Chem Lett 23:3064-9. 2013
  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 Broad-spectrum efficacy across cognitive domains by alpha7 nicotinic acetylcholine receptor agonism correlates with activation of ERK1/2 and CREB phosphorylation pathways
    Robert S Bitner
    Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, Illinois 60064, USA
    J Neurosci 27:10578-87. 2007
  10. ncbi 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

Research Grants

Detail Information

Publications291 found, 100 shown here

  1. pmc AP24534, a pan-BCR-ABL inhibitor for chronic myeloid leukemia, potently inhibits the T315I mutant and overcomes mutation-based resistance
    Thomas O'Hare
    Division of Hematology and Medical Oncology, Oregon Health and Science University Knight Cancer Institute, Portland, OR 97239, USA
    Cancer Cell 16:401-12. 2009
    ..Our work supports clinical evaluation of AP24534 as a pan-BCR-ABL inhibitor for treatment of CML...
  2. 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...
  3. ncbi 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...
  4. ncbi Levosimendan protection against kidney ischemia/reperfusion injuries in anesthetized pigs
    Elena Grossini
    Department of Translational Medicine, University East Piedmont, Via Solaroli 17, I 28100 Novara, Italy
    J Pharmacol Exp Ther 342:376-88. 2012
    ....
  5. 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...
  6. ncbi Levosimendan preserves the contractile responsiveness of hypoxic human myocardium via mitochondrial K(ATP) channel and potential pERK 1/2 activation
    Paul F Soeding
    Cardiovascular Therapeutics Unit, Department of Pharmacology, University of Melbourne, Parkville, Australia
    Eur J Pharmacol 655:59-66. 2011
    ..The significant increase in the activity of prosurvival mediators ERK 1/2 and P38 following hypoxia indicates a potential mechanism of action for levosimendan-induced cardioprotection...
  7. pmc Substituted imidazopyridazines are potent and selective inhibitors of Plasmodium falciparum calcium-dependent protein kinase 1 (PfCDPK1)
    Timothy M Chapman
    Centre for Therapeutics Discovery, MRC Technology, Mill Hill, London NW7 1AD, UK
    Bioorg Med Chem Lett 23:3064-9. 2013
    ..Initial in vivo testing has revealed good oral bioavailability in a mouse PK study and modest in vivo efficacy in a Plasmodium berghei mouse model of malaria...
  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 Broad-spectrum efficacy across cognitive domains by alpha7 nicotinic acetylcholine receptor agonism correlates with activation of ERK1/2 and CREB phosphorylation pathways
    Robert S Bitner
    Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, Illinois 60064, USA
    J Neurosci 27:10578-87. 2007
    ....
  10. ncbi 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...
  11. 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...
  12. 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...
  13. 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...
  14. ncbi 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
    ....
  15. 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...
  16. ncbi Receptors with different affinities mediate phasic and tonic GABA(A) conductances in hippocampal neurons
    Brandon M Stell
    Department of Neurology, University of California Los Angeles School of Medicine, Los Angeles, California 90095, USA
    J Neurosci 22:RC223. 2002
    ..These findings are consistent with tonic and phasic conductances being mediated by different GABA(A) receptor subtypes with different affinities for GABA...
  17. pmc Imidazopyridazines as potent inhibitors of Plasmodium falciparum calcium-dependent protein kinase 1 (PfCDPK1): Preparation and evaluation of pyrazole linked analogues
    Jonathan M Large
    Centre for Therapeutics Discovery, MRC Technology, Mill Hill, London NW7 1AD, UK Electronic address
    Bioorg Med Chem Lett 23:6019-24. 2013
    ..These new analogues thus provide a credible additional route to further development of the series. ..
  18. 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...
  19. pmc γ-Aminobutyric acid (GABA) signalling in human pancreatic islets is altered in type 2 diabetes
    J Taneera
    Department of Clinical Sciences, Lund University Diabetes Center, University Hospital Malmo, Lund University, Malmo, Sweden
    Diabetologia 55:1985-94. 2012
    ..We examined the expression and function of the GABA signalling system components in human pancreatic islets from normoglycaemic and type 2 diabetic individuals...
  20. ncbi Effects of levosimendan on the energy balance: preclinical and clinical evidence
    Markku S Nieminen
    Division of Cardiology, Helsinki University Central Hospital, Helsinki, Finland
    J Cardiovasc Pharmacol 53:302-10. 2009
    ..Moreover, levosimendan-evoked KATP channel opening may possess favorable effects on mitochondrial adenosine triphosphate synthesis conferring cardioprotection during ischemic insults...
  21. ncbi Biological activity and preclinical efficacy of azetidinyl pyridazines as potent systemically-distributed stearoyl-CoA desaturase inhibitors
    Elise Isabel
    Merck Frosst Centre for Therapeutic Research, PO Box 1005, Pointe Claire Dorval, Quebec, Canada
    Bioorg Med Chem Lett 21:479-83. 2011
    ..In preparation for an HTS campaign, a radiolabeled azetidinyl pyridazine displaying low non-specific binding in the scintillation proximity assay was prepared...
  22. ncbi 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...
  23. ncbi Levosimendan
    D P Figgitt
    Adis International Limited, Auckland, New Zealand
    Drugs 61:613-27; discussion 628-9. 2001
    ..Levosimendan has shown no clinically important pharmacokinetic interactions with captopril, felodipine, beta-blockers, digoxin, warfarin, isosorbide-5-mononitrate, carvedilol, alcohol (ethanol) or itraconazole...
  24. ncbi Levosimendan: a review of its use in the management of acute decompensated heart failure
    Carmen A Innes
    Adis International Limited, Auckland, New Zealand
    Drugs 63:2651-71. 2003
    ..More patients receiving dobutamine than those receiving levosimendan experienced angina pectoris/chest pain/myocardial ischaemia or rate/rhythm disorders...
  25. pmc A review of pulmonary arterial hypertension: role of ambrisentan
    Robyn J Barst
    New York Presbyterian Pulmonary Hypertension Center, Columbia University College of Physicians and Surgeons, 3959 Broadway, BHN 2 255, NewYork, NY 10032, USA
    Vasc Health Risk Manag 3:11-22. 2007
    ..The demonstration of clinical efficacy, low incidence of acute hepatic toxicity, and low risk of drug-drug interactions support the role of ambrisentan for the treatment of PAH...
  26. 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...
  27. ncbi 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...
  28. 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...
  29. ncbi 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...
  30. 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...
  31. ncbi Clinical pharmacokinetics and pharmacodynamics of etravirine
    Monika Schöller-Gyüre
    Tibotec BVBA, Generaal De Wittelaan L11B 3, Mechelen B 2800, Belgium
    Clin Pharmacokinet 48:561-74. 2009
    ..In the two phase III trials DUET-1 and DUET-2, no relationship was demonstrated between the pharmacokinetics of etravirine and the primary efficacy endpoint of viral load below 50 copies/mL or the safety profile of etravirine...
  32. ncbi The Ca2+-sensitizer levosimendan improves oxidative damage, BNP and pro-inflammatory cytokine levels in patients with advanced decompensated heart failure in comparison to dobutamine
    Catherine Avgeropoulou
    State Cardiology Department, Hippokration Hospital, 114 Vassilissis Sophias, Athens, Greece
    Eur J Heart Fail 7:882-7. 2005
    ....
  33. ncbi Sustained hemodynamic effects of intravenous levosimendan
    Matti Kivikko
    Orion Pharma, Clinical Research, Espoo, Finland
    Circulation 107:81-6. 2003
    ..The goal of this study was to determine whether the hemodynamic effects of Levo are sustained during a long-term infusion and beyond the discontinuation of drug infusion...
  34. 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...
  35. pmc Levosimendan inhibits release of reactive oxygen species in polymorphonuclear leukocytes in vitro and in patients with acute heart failure and septic shock: a prospective observational study
    Julia Hasslacher
    Intensive Care Unit and Laboratory of Inflammatory Research, Department of Internal Medicine I, Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria
    Crit Care 15:R166. 2011
    ..The aim of our study was to explore the influence of levosimendan on polymorphonuclear leucocytes (PMN), a main source of reactive oxygen species, in vitro and in patients with acute heart failure or septic myocardial depression...
  36. ncbi Levosimendan improves renal function in patients with advanced chronic heart failure awaiting cardiac transplantation
    Gregor Zemljic
    Advanced Heart Failure and Transplantation Center, Division of Cardiology, Ljubljana University Medical Center, Ljubljana, Slovenia
    J Card Fail 13:417-21. 2007
    ..Long-term impact of levosimendan on renal function remains undefined. Prospectively, we evaluated effects of levosimendan on renal function in patients with advanced chronic heart failure awaiting cardiac transplantation...
  37. 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...
  38. 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...
  39. 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...
  40. 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...
  41. 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...
  42. ncbi Efficacy and safety of TMC125 (etravirine) in treatment-experienced HIV-1-infected patients in DUET-1: 24-week results from a randomised, double-blind, placebo-controlled trial
    José Valdez Madruga
    Centro de Referência e Treinamento DST AIDS, Sao Paulo, Brazil
    Lancet 370:29-38. 2007
    ..The aim of this trial was to assess the efficacy, safety, and tolerability of TMC125 (etravirine), a non-nucleoside reverse transcriptase inhibitor (NNRTI)...
  43. ncbi Levosimendan protects against experimental endotoxemic acute renal failure
    Richard A Zager
    Department of Medicine, University of Washington, Seattle, USA
    Am J Physiol Renal Physiol 290:F1453-62. 2006
    ..This suggests that LS, and other K(ATP) channel agonists, have a margin of safety if employed in situations (sepsis syndrome, heart failure) in which severe renal vasoconstriction might lead to ischemic ARF...
  44. 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
    ....
  45. ncbi A 6-month follow-up of intermittent levosimendan administration effect on systolic function, specific activity questionnaire, and arrhythmia in advanced heart failure
    Sophie Mavrogeni
    Onassis Cardiac Surgery Center, Athens, Greece
    J Card Fail 13:556-9. 2007
    ..We administrated LS on a monthly intermittent 24-hour protocol and evaluated the clinical effect after 6 months in a randomized, open, prospective study...
  46. 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
    ....
  47. 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...
  48. ncbi 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...
  49. 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...
  50. 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...
  51. 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...
  52. 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...
  53. 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...
  54. 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...
  55. ncbi Levosimendan in cardiac surgery: current best available evidence
    Shahzad G Raja
    Department of Cardiac Surgery, Royal Hospital for Sick Children, Glasgow, United Kingdom
    Ann Thorac Surg 81:1536-46. 2006
    ..This review article briefly discusses the pharmacology of levosimendan and evaluates current best available evidence to assess the safety and efficacy of levosimendan usage in cardiac surgery...
  56. ncbi Synthesis and in vitro evaluation of imidazopyridazines as novel inhibitors of the malarial kinase PfPK7
    Nathalie Bouloc
    Drug Discovery Group, MRC Technology, 1 3 Burtonhole Lane, Mill Hill, London NW7 1AD, UK
    Bioorg Med Chem Lett 18:5294-8. 2008
    ..Although these compounds show likely broad spectrum inhibitory activity, they represent a useful starting point for further chemical optimisation...
  57. pmc Agents with inotropic properties for the management of acute heart failure syndromes. Traditional agents and beyond
    John R Teerlink
    San Francisco Veterans Affairs Medical Center, University of California, USA
    Heart Fail Rev 14:243-53. 2009
    ....
  58. pmc TMC125 displays a high genetic barrier to the development of resistance: evidence from in vitro selection experiments
    Johan Vingerhoets
    Tibotec, Mechelen, Belgium
    J Virol 79:12773-82. 2005
    ..These results demonstrate that TMC125 has a unique profile of activity against NNRTI-resistant virus and possesses a high genetic barrier to the development of resistance in vitro...
  59. ncbi Calcium sensitizer agents: a new class of inotropic agents in the treatment of decompensated heart failure
    Sergio V Perrone
    Heart Failure, Fundacion para la Lucha contra las Enfermedades Neurologicas de la Infancia, Instituto de Investigaciones Neurologicas Raul Carrea, FLENI, Montaneses 2325, Buenos Aires C1428AQK, Argentina
    Int J Cardiol 103:248-55. 2005
    ..Available clinical data suggest that calcium sensitizer agents represent a promising class of inotropic agents in a field that has seen few advances in recent decades...
  60. 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...
  61. ncbi Effects of calcium sensitizer OR-1986 on a cardiovascular mortality and myocardial remodelling in hypertensive Dahl/Rapp rats
    M Louhelainen
    Institute of Biomedicine, Pharmacology, University of Helsinki, Finland
    J Physiol Pharmacol 60:41-7. 2009
    ..The present study also underscores the importance of cellular senescence in the pathogenesis of salt-induced hypertensive heart disease...
  62. ncbi De novo and molecular target-independent discovery of orally bioavailable lead compounds for neurological disorders
    Laura K Wing
    Center for Drug Discovery and Chemical Biology, Northwestern University, Chicago, IL, USA
    Curr Alzheimer Res 3:205-14. 2006
    ..For the AD case study, novel lead compounds were developed in less than two years by a small academic group, and corporate sponsored clinical trials are planned...
  63. 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...
  64. ncbi The influence of levosimendan and iloprost on renal ischemia-reperfusion: an experimental study
    Necmettin Yakut
    Department of Cardiovascular Surgery, Ataturk Education and Research Hospital, Izmir, Turkey
    Interact Cardiovasc Thorac Surg 7:235-9. 2008
    ..Iloprost and pentoxyfillin reduced renal ischemia-reperfusion injury in rabbit model. There was no significant difference between these two medications...
  65. ncbi Repeated infusions of levosimendan: well tolerated and improves functional capacity in decompensated heart failure - a single-centre experience
    N M Parle
    Advanced Heart Failure and Cardiac Transplant Service, Royal Perth Hospital, Wellington Street, GPO Box X2213, Perth 6847, Western Australia, Australia
    Heart Lung Circ 17:206-10. 2008
    ..Recent clinical studies have demonstrated that single doses of levosimendan have positive symptomatic and haemodynamic benefits, few have explored the efficacy and safety of intermittent repeated doses of levosimendan...
  66. ncbi Levosimendan improves LV systolic and diastolic performance at rest and during exercise after heart failure
    Hideo Tachibana
    Cardiology Section, Wake Forest University School of Medicine, Winston Salem, North Carolina 27157 1045, USA
    Am J Physiol Heart Circ Physiol 288:H914-22. 2005
    ..After CHF, LSM produced arterial vasodilatation; improved LV relaxation and diastolic filling; increased contractility, LV arterial coupling, and mechanical efficiency; and normalized the response to Ex...
  67. 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...
  68. ncbi Levosimendan modulates programmed forms of cell death through K(ATP) channels and nitric oxide
    Francesca Uberti
    Laboratorio di Fisiologia, Dipartimento di Medicina Clinica e Sperimentale, Universita degli Studi del Piemonte Orientale A Avogadro, Via Solaroli 17 and Chirurgia Sperimentale, Azienda Ospedaliera Universitaria Maggiore Della Carità, corso Mazzini 36, Novara, Italy
    J Cardiovasc Pharmacol 57:246-58. 2011
    ..The mitoK(ATP) channels and NO may be involved in such cardioprotection through interference with mitochondrial functioning...
  69. ncbi Levosimendan increases diastolic coronary flow in isolated guinea-pig heart by opening ATP-sensitive potassium channels
    P Kaheinen
    Orion Pharma, Drug Discovery and Pharmacology, Cardiovascular Research, Espoo, Finland
    J Cardiovasc Pharmacol 37:367-74. 2001
    ..The additive effect of bisindolylmaleimide and levosimendan on the increase of DCFV suggests that the latter binds to the unphosphorylated form of the channel...
  70. ncbi Management of acute cardiac failure by intracoronary administration of levosimendan
    Philippe P Caimmi
    Department of Cardiac Surgery, Azienda Ospedaliero Universitaria Maggiore della Carita, Italy
    J Cardiovasc Pharmacol 58:246-53. 2011
    ..Therefore, IC Levosimendan administration in acute heart failure is safe and efficacious producing improved cardiac function without significant detrimental hypotension...
  71. ncbi No beneficial effects of levosimendan in acute porcine endotoxaemia
    Michelle S Chew
    Department of Intensive Care Medicine, Skåne University Hospital Malmö, Lund University, Sweden
    Acta Anaesthesiol Scand 55:851-61. 2011
    ..The secondary aims were to investigate its effect on renal and liver function, and the plasma cytokine response...
  72. ncbi Effects of combined arginine vasopressin and levosimendan on organ function in ovine septic shock
    Sebastian Rehberg
    Department of Anesthesiology and Intensive Care, University of Muenster, Muenster, Germany
    Crit Care Med 38:2016-23. 2010
    ..To compare the effects of a first-line therapy of combined arginine vasopressin, levosimendan, and norepinephrine with arginine vasopressin + norepinephrine or norepinephrine alone in ovine septic shock...
  73. 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...
  74. ncbi Sequential steps underlying neuronal plasticity induced by a transient exposure to gabazine
    Silvia Pegoraro
    International School for Advanced Studies, Area Science Park, Trieste, Italy
    J Cell Physiol 222:713-28. 2010
    ..iii) Genes in Cluster 3 are up-regulated at 24 h and are involved in cellular homeostasis. This approach allows relating different steps of neuronal plasticity to specific transcriptional profiles...
  75. ncbi Effects of levosimendan on renal function in patients undergoing coronary artery surgery
    Anne Ristikankare
    Department of Anaesthesiology and Intensive Care, Helsinki University Central Hospital, Helsinki, Finland
    J Cardiothorac Vasc Anesth 26:591-5. 2012
    ..To evaluate the effect of levosimendan on postoperative renal function in patients with compromised heart function undergoing on-pump coronary artery bypass graft surgery...
  76. ncbi Preoperative levosimendan infusion in combined aortic valve and coronary bypass surgery
    H Leppikangas
    Department of Anaesthesia, Tampere University Hospital, PO Box 2000, Tampere 33521, Finland
    Br J Anaesth 106:298-304. 2011
    ..The aim of this study was to evaluate the haemodynamic effects of preoperative levosimendan in patients undergoing high-risk cardiac surgery...
  77. ncbi 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
    ....
  78. 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...
  79. ncbi 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...
  80. 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...
  81. 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...
  82. ncbi 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...
  83. 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...
  84. ncbi 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...
  85. 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...
  86. 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
    ....
  87. 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...
  88. 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
    ....
  89. ncbi 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)...
  90. 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...
  91. 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...
  92. 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...
  93. ncbi 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...
  94. 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)...
  95. 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...
  96. 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...
  97. ncbi 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...
  98. 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
  99. 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
    ....
  100. 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...
  101. 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...

Research Grants32

  1. 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. ..
  2. HIV-Related Proteinuria and Endothelial Dysfunction
    Samir Gupta; Fiscal Year: 2007
    ..Dub6) in the fields of HIV metabolic and renal complications, renal vascular and glomerular pathology, and clinical trials design and implementation. ..
  3. Topomer selection by chemists from All structures
    Richard Cramer; Fiscal Year: 2006
    ..abstract_text> ..
  4. Clozapine Treatment of Schizophrenic Patients
    Robert Buchanan; Fiscal Year: 2006
    ..The study will provide new information on the clinical utility of adjunctive risperidone in treatment-resistant patients who fail to adequately respond to clozapine. ..
  5. 5-LIPOXYGENASE PRODUCTS IN ASTHMATIC IMMUNE RESPONSE
    William Henderson; Fiscal Year: 2008
    ..abstract_text> ..
  6. Effect of Daily Exercise on Cardiac Autonomic Regulation
    GEORGE BILLMAN; Fiscal Year: 2005
    ..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. ..
  7. Convergent central pathways for sympatho-inhibition
    CARON DEAN BERNHOFT; Fiscal Year: 2005
    ..These novel data will be of potential significance to an array of pathologies and behaviors including emotional behaviors, analgesia, shock, sexual function and fainting. ..
  8. Advanced Centers for Interventions and Services Research
    Robert Buchanan; Fiscal Year: 2007
    ....
  9. NO AND OXIDATIVE STRESS IN HUMAN MYOCARDIAL FAILURE
    Michael Givertz; Fiscal Year: 2003
    ..abstract_text> ..
  10. TNF-ALPHA REGULATION OF AT1 RECEPTOR & POST-MI FIBROSIS
    Barry Greenberg; Fiscal Year: 2003
    ..This information will provide important insights into the pathogenesis of post-MI fibrosis. ..
  11. Dendritic Processing in the Olfactory Bulb
    Jason Christie; Fiscal Year: 2003
    ..The specific aims are: (1) to determine the function of autoexcitation in mitral cell processing and (2) to determine how dendritic compartmentalization effects mitral cell processing. ..
  12. NOVEL NON-PEPTIDE ANTAGONIST OF THE MCH RECEPTOR
    David Schwarz; Fiscal Year: 2003
    ..Compounds successfully emerging from this process will be further evaluated in acute and chronic feeding paradigms in order to select candidates suitable for clinical trials. ..
  13. The Effects of the Cannabinoid-1 Receptor Antagonist Rimonabant on Weight...
    Robert Buchanan; Fiscal Year: 2008
    ..There should be direct evidence of efficacy and safety in these patients in order to provide truly effective treatments and further understanding of these disorders. [unreadable] [unreadable] [unreadable]..
  14. MOTOR CORTEX AND THALAMOCORTICAL NETWORK IN LOCOMOTION
    IRINA BELOOZEROVA; Fiscal Year: 2002
    ..compare with those of cortical neurons? What are the characteristics of the synaptic linkages between VL projection neurons and cortical recipient neurons and how do these linkages change under different conditions of locomotion? ..
  15. Dietary Omega-3 Fatty Acids and Sudden Cardiac Death
    GEORGE EDWARD BILLMAN; Fiscal Year: 2010
    ..This project will also determine the effectiveness of fish oil supplements in reducing sudden death due to a lethal abnormal heart rhythm after a heart attack. ..
  16. Northeast Under/Grad Research Organization for Neuroscience
    Cheryl Frye; Fiscal Year: 2008
    ..Both of these outcomes are congruous with the Public Health Service's mission to ensure that there is a resource of well-trained scientists and health-care providers in the United States. [unreadable] [unreadable] [unreadable]..
  17. 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. ..
  18. BLOOD PRESSURE CONTROL BY FOREBRAIN & BRAINSTEM NEURONS
    SUSAN BARMAN; Fiscal Year: 2008
    ..unreadable] [unreadable]..
  19. ACUTE RENAL FAILURE--IMPACT OF FLUORINATED ANESTHETICS
    RICHARD ZAGER; Fiscal Year: 2001
    ....
  20. Altered Function of a GABA-A receptor epilepsy mutation
    Mathew Jones; Fiscal Year: 2007
    ..abstract_text> ..
  21. 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. ..
  22. Genes Underlying the Response to Inhaled Anesthetics
    James Sonner; Fiscal Year: 2008
    ....
  23. Nonhuman Primate Model of Benzodiazepine Relapse
    JAMES ROWLETT; Fiscal Year: 2002
    ....
  24. 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. ..
  25. SLEEP/WAKE-RELATED NEURONAL ACTIVITY IN THE
    Gerald Marks; Fiscal Year: 2002
    ..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. ..
  26. ORAL TOLERANCE IN PLP INDUCED EAE--MOLECULAR MECHANISMS
    William Karpus; Fiscal Year: 2003
    ..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. ..
  27. Pulmonary Hypertension Scientific Conference
    Michael McGoon; Fiscal Year: 2004
    ....
  28. Functional Analysis of GABAerglc Sedative/Anxiolytics
    NANCY ATOR; Fiscal Year: 2007
    ..abstract_text> ..
  29. 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. ..
  30. Role of NTS POMC neurons in energy homeostasis
    SUZANNE APPLEYARD; Fiscal Year: 2008
    ..abstract_text> ..
  31. 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. ..