valproic acid

Summary

Summary: A fatty acid with anticonvulsant properties used in the treatment of epilepsy. The mechanisms of its therapeutic actions are not well understood. It may act by increasing GAMMA-AMINOBUTYRIC ACID levels in the brain or by altering the properties of voltage dependent sodium channels.

Top Publications

  1. pmc Attenuation of phospholipid signaling provides a novel mechanism for the action of valproic acid
    Xuehua Xu
    School of Biological Sciences, Royal Holloway University of London, Egham, United Kingdom
    Eukaryot Cell 6:899-906. 2007
  2. pmc Valproic acid defines a novel class of HDAC inhibitors inducing differentiation of transformed cells
    M Gottlicher
    Forschungszentrum Karlsruhe, Institute of Toxicology and Genetics, H v Helmholtz Platz 1, D 76344 Eggenstein, Germany
    EMBO J 20:6969-78. 2001
  3. ncbi Histone deacetylase is a direct target of valproic acid, a potent anticonvulsant, mood stabilizer, and teratogen
    C J Phiel
    Howard Hughes Medical Institute, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6148, USA
    J Biol Chem 276:36734-41. 2001
  4. pmc Histone deacetylase inhibition-mediated neuronal differentiation of multipotent adult neural progenitor cells
    Jenny Hsieh
    Laboratory of Genetics, The Salk Institute, La Jolla, CA 92037, USA
    Proc Natl Acad Sci U S A 101:16659-64. 2004
  5. pmc The histone deacetylase inhibitor valproic acid selectively induces proteasomal degradation of HDAC2
    Oliver H Kramer
    Georg Speyer Haus, Paul Ehrlich Strasse 42 44, D 60596 Frankfurt, Germany
    EMBO J 22:3411-20. 2003
  6. ncbi Induction of pluripotent stem cells by defined factors is greatly improved by small-molecule compounds
    Danwei Huangfu
    Department of Stem Cell and Regenerative Biology, Howard Hughes Medical Institute, Harvard Stem Cell Institute, Harvard University, 7 Divinity Avenue, Cambridge, Massachusetts 02138, USA
    Nat Biotechnol 26:795-7. 2008
  7. ncbi Valproic acid in association with highly active antiretroviral therapy for reducing systemic HIV-1 reservoirs: results from a multicentre randomized clinical study
    J P Routy
    Division of Hematology, Royal Victoria Hospital, McGill University Health Centre, Montreal, QC, Canada
    HIV Med 13:291-6. 2012
  8. pmc Therapeutic potential of mood stabilizers lithium and valproic acid: beyond bipolar disorder
    Chi Tso Chiu
    Molecular Neurobiology Section, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland, USA
    Pharmacol Rev 65:105-42. 2013
  9. ncbi Synergistic induction of p53 mediated apoptosis by valproic acid and nutlin-3 in acute myeloid leukemia
    E McCormack
    Department of Medicine, Hematology Section, Haukeland University Hospital, Bergen, Norway
    Leukemia 26:910-7. 2012
  10. ncbi Phase I study of decitabine alone or in combination with valproic acid in acute myeloid leukemia
    William Blum
    Department of Medicine, Division of Hematology and Oncology, The Ohio State University, Columbus, OH 43210, USA
    J Clin Oncol 25:3884-91. 2007

Detail Information

Publications303 found, 100 shown here

  1. pmc Attenuation of phospholipid signaling provides a novel mechanism for the action of valproic acid
    Xuehua Xu
    School of Biological Sciences, Royal Holloway University of London, Egham, United Kingdom
    Eukaryot Cell 6:899-906. 2007
    b>Valproic acid (VPA) is used to treat epilepsy and bipolar disorder and to prevent migraine. It is also undergoing trials for cancer therapy. However, the biochemical and molecular biological actions of VPA are poorly understood...
  2. pmc Valproic acid defines a novel class of HDAC inhibitors inducing differentiation of transformed cells
    M Gottlicher
    Forschungszentrum Karlsruhe, Institute of Toxicology and Genetics, H v Helmholtz Platz 1, D 76344 Eggenstein, Germany
    EMBO J 20:6969-78. 2001
    ..Here, we show that the well-tolerated antiepileptic drug valproic acid is a powerful HDAC inhibitor...
  3. ncbi Histone deacetylase is a direct target of valproic acid, a potent anticonvulsant, mood stabilizer, and teratogen
    C J Phiel
    Howard Hughes Medical Institute, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6148, USA
    J Biol Chem 276:36734-41. 2001
    b>Valproic acid is widely used to treat epilepsy and bipolar disorder and is also a potent teratogen, but its mechanisms of action in any of these settings are unknown...
  4. pmc Histone deacetylase inhibition-mediated neuronal differentiation of multipotent adult neural progenitor cells
    Jenny Hsieh
    Laboratory of Genetics, The Salk Institute, La Jolla, CA 92037, USA
    Proc Natl Acad Sci U S A 101:16659-64. 2004
    ..Here, we show that an inhibitor of histone deacetylase, valproic acid (VPA), induced neuronal differentiation of adult hippocampal neural progenitors...
  5. pmc The histone deacetylase inhibitor valproic acid selectively induces proteasomal degradation of HDAC2
    Oliver H Kramer
    Georg Speyer Haus, Paul Ehrlich Strasse 42 44, D 60596 Frankfurt, Germany
    EMBO J 22:3411-20. 2003
    ..We show that HDAC2 undergoes basal turnover by the ubiquitin-proteasome pathway. Valproic acid (VPA), in addition to selectively inhibiting the catalytic activity of class I HDACs, induces proteasomal ..
  6. ncbi Induction of pluripotent stem cells by defined factors is greatly improved by small-molecule compounds
    Danwei Huangfu
    Department of Stem Cell and Regenerative Biology, Howard Hughes Medical Institute, Harvard Stem Cell Institute, Harvard University, 7 Divinity Avenue, Cambridge, Massachusetts 02138, USA
    Nat Biotechnol 26:795-7. 2008
    ..In particular, valproic acid (VPA), an HDAC inhibitor, improves reprogramming efficiency by more than 100-fold, using Oct4-GFP as a ..
  7. ncbi Valproic acid in association with highly active antiretroviral therapy for reducing systemic HIV-1 reservoirs: results from a multicentre randomized clinical study
    J P Routy
    Division of Hematology, Royal Victoria Hospital, McGill University Health Centre, Montreal, QC, Canada
    HIV Med 13:291-6. 2012
    Conflicting results have been reported regarding the ability of valproic acid (VPA) to reduce the size of HIV reservoirs in patients receiving suppressive highly active antiretroviral therapy (HAART)...
  8. pmc Therapeutic potential of mood stabilizers lithium and valproic acid: beyond bipolar disorder
    Chi Tso Chiu
    Molecular Neurobiology Section, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland, USA
    Pharmacol Rev 65:105-42. 2013
    The mood stabilizers lithium and valproic acid (VPA) are traditionally used to treat bipolar disorder (BD), a severe mental illness arising from complex interactions between genes and environment that drive deficits in cellular ..
  9. ncbi Synergistic induction of p53 mediated apoptosis by valproic acid and nutlin-3 in acute myeloid leukemia
    E McCormack
    Department of Medicine, Hematology Section, Haukeland University Hospital, Bergen, Norway
    Leukemia 26:910-7. 2012
    ..We hypothesized that co-inhibition of MDM2 and HDACs, with nutlin-3 and valproic acid (VPA) would additively inhibit growth in leukemic cells expressing wild type TP53 and induce p53-mediated ..
  10. ncbi Phase I study of decitabine alone or in combination with valproic acid in acute myeloid leukemia
    William Blum
    Department of Medicine, Division of Hematology and Oncology, The Ohio State University, Columbus, OH 43210, USA
    J Clin Oncol 25:3884-91. 2007
    To determine an optimal biologic dose (OBD) of decitabine as a single agent and then the maximum-tolerated dose (MTD) of valproic acid (VA) combined with decitabine in acute myeloid leukemia (AML).
  11. pmc Histone modifications around individual BDNF gene promoters in prefrontal cortex are associated with extinction of conditioned fear
    Timothy W Bredy
    Department of Psychiatry and Biobehavioral Sciences, Brain Research Institute, Semel Institute for Neuroscience and Human Behavior, Los Angeles, California 90095, USA
    Learn Mem 14:268-76. 2007
    ..b>Valproic acid (VPA), used for some time as an anticonvulsant and a mood stabilizer, modulates the expression of BDNF, and is ..
  12. pmc Depletion of latent HIV-1 infection in vivo: a proof-of-concept study
    Ginger Lehrman
    University of Texas Southwestern Medical Center at Dallas, Department of Medicine, Division of Infectious Diseases, 5323 Harry Hines Boulevard, Dallas, TX 753901, USA
    Lancet 366:549-55. 2005
    ..Since the chromatin remodeling enzyme histone deacetylase 1 (HDAC1) maintains latency of integrated HIV, we tested the ability of the HDAC inhibitor valproic acid to deplete persistent, latent infection in resting CD4+ T cells.
  13. ncbi Induction of HDAC2 expression upon loss of APC in colorectal tumorigenesis
    Ping Zhu
    Institute of Toxicology and Genetics, Forschungszentrum Karlsruhe Branch, H v H Platz 1, D 76344 Eggenstein, Germany
    Cancer Cell 5:455-63. 2004
    ..Interference with HDAC2 by valproic acid largely diminishes adenoma formation in APC(min) mice...
  14. ncbi Safety of long-term treatment of HAM/TSP patients with valproic acid
    Stephane Olindo
    Service de Neurologie, Centre Hospitalier Universitaire de Fort de France, Martinique, France
    Blood 118:6306-9. 2011
    ..approach, we previously suggested reducing the proviral load by modulating lysine deacetylase activity using valproic acid (VPA) and exposing virus-positive cells to the host immune response...
  15. pmc The histone deacetylase inhibitor valproic acid lessens NK cell action against oncolytic virus-infected glioblastoma cells by inhibition of STAT5/T-BET signaling and generation of gamma interferon
    Christopher A Alvarez-Breckenridge
    Medical Scientist Training Program, The Ohio State University Medical Center and The James Cancer Hospital and Solove Research Institute, Columbus, Ohio, USA
    J Virol 86:4566-77. 2012
    ..viral oncolysis, consisting of the interferon (IFN) response induced by viral infection, is inhibited by valproic acid (VPA) and other histone deacetylase inhibitors (HDACi)...
  16. ncbi A double-blind, placebo-controlled, randomized phase III trial of chemotherapy plus epigenetic therapy with hydralazine valproate for advanced cervical cancer. Preliminary results
    Jaime Coronel
    Division of Clinical Research, Instituto Nacional de Cancerologia, Mexico City, Mexico
    Med Oncol 28:S540-6. 2011
    ..Molecular correlates with response and survival from this trial are pending to analyze...
  17. pmc The histone deacetylase inhibitor valproic acid enhances acquisition, extinction, and reconsolidation of conditioned fear
    Timothy W Bredy
    Semel Institute for Neuroscience and Human Behavior, UCLA, Los Angeles, California 90095, USA
    Learn Mem 15:39-45. 2008
    ..b>Valproic acid (VPA), used for many years as an anticonvulsant and a mood stabilizer, has effects on learning and memory and ..
  18. ncbi Induction of pluripotent stem cells from primary human fibroblasts with only Oct4 and Sox2
    Danwei Huangfu
    Department of Stem Cell and Regenerative Biology, Howard Hughes Medical Institute, Harvard Stem Cell Institute, Harvard University, 7 Divinity Avenue, Cambridge, Massachusetts 02138, USA
    Nat Biotechnol 26:1269-75. 2008
    ..Here we report that valproic acid (VPA), a histone deacetylase inhibitor, enables reprogramming of primary human fibroblasts with only two ..
  19. ncbi Valproate protects cells from ER stress-induced lipid accumulation and apoptosis by inhibiting glycogen synthase kinase-3
    Anna J Kim
    Department of Biochemistry, McMaster University, Hamilton, Ontario, L8S 4LB, Canada
    J Cell Sci 118:89-99. 2005
    ..Strategies to protect cells from agents/conditions that induce ER stress may have potential in the treatment of the growing number of diseases and disorders linked to ER dysfunction...
  20. ncbi Transcriptomic concentration-response evaluation of valproic acid, cyproconazole, and hexaconazole in the neural embryonic stem cell test (ESTn)
    Peter T Theunissen
    Laboratory for Health Protection Research, National Institute for Public Health and the Environment RIVM, 3720 BA Bilthoven, The Netherlands
    Toxicol Sci 125:430-8. 2012
    ..developmental toxicants, two triazoles, cyproconazole (CYP) and hexaconazole (HEX), and the anticonvulsant valproic acid (VPA)...
  21. ncbi Valproic acid-mediated neuroprotection in retinal ischemia injury via histone deacetylase inhibition and transcriptional activation
    Zhenzhen Zhang
    Department of Ophthalmology, Shanghai Jiaotong University Affiliated Shanghai First People s Hospital, Wujin Road 85, Shanghai 200080, China
    Exp Eye Res 94:98-108. 2012
    ..The pathogenesis of retinal ischemia involves changes in gene expression. Valproic acid (VPA), a broad-spectrum histone deacetylase inhibitor, is an anticonvulsant and mood-stabilizing drug with ..
  22. pmc Valproic acid confers functional pluripotency to human amniotic fluid stem cells in a transgene-free approach
    Dafni Moschidou
    Imperial College London, London, UK
    Mol Ther 20:1953-67. 2012
    ..in human embryonic stem cell (hESC) medium supplemented with the histone deacetylase inhibitor (HDACi) valproic acid (VPA)...
  23. ncbi Valproate induces replication-independent active DNA demethylation
    Nancy Detich
    Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec H3G 1Y6 Canada
    J Biol Chem 278:27586-92. 2003
    In this report, we demonstrate that valproic acid (VPA), a drug that has been used for decades in the treatment of epilepsy and as a mood stabilizer, triggers replication-independent active demethylation of DNA...
  24. pmc Prolonged survival with valproic acid use in the EORTC/NCIC temozolomide trial for glioblastoma
    M Weller
    Department of Neurology, University Hospital Zurich, Frauenklinikstrasse 26, CH 8091 Zurich, Switzerland
    Neurology 77:1156-64. 2011
    ..This analysis was performed to assess whether antiepileptic drugs (AEDs) modulate the effectiveness of temozolomide radiochemotherapy in patients with newly diagnosed glioblastoma...
  25. ncbi In vivo evidence in the brain for lithium inhibition of glycogen synthase kinase-3
    Todd D Gould
    Laboratory of Molecular Pathophysiology, Mood and Anxiety Disorders Program, National Institute of Mental Health, Bethesda, MD 20892 4405, USA
    Neuropsychopharmacology 29:32-8. 2004
    ..These results strongly suggest that lithium significantly inhibits brain glycogen synthase kinase-3 in vivo at concentrations relevant for the treatment of bipolar disorder...
  26. pmc Valproic acid attenuates proteinuria and kidney injury
    Katrien Van Beneden
    Department of Human Anatomy, Liver Cell Biology Lab, Vrije Universiteit Brussel, Brussels, Belgium
    J Am Soc Nephrol 22:1863-75. 2011
    ..Here, we studied the effect of valproic acid in adriamycin-induced nephropathy in mice...
  27. ncbi The neuroprotective agent, valproic acid, regulates the mitogen-activated protein kinase pathway through modulation of protein kinase A signalling in Dictyostelium discoideum
    Katrina Boeckeler
    Department of Biology and the Wolfson Institute for Biomedical Research, University College London, London WC1E 6BT, UK
    Eur J Cell Biol 85:1047-57. 2006
    ..The bipolar disorder treatment, valproic acid (VPA), increases the activity of this pathway by modulating extracellular signal-regulated kinase 2 (ERK2) ..
  28. pmc Pluripotency-related, valproic acid (VPA)-induced genome-wide histone H3 lysine 9 (H3K9) acetylation patterns in embryonic stem cells
    Hadas Hezroni
    Department of Genetics, The Institute of Life Sciences, Hebrew University of Jerusalem, Edmond J Safra Campus, Jerusalem 91904, Israel
    J Biol Chem 286:35977-88. 2011
    ..and gene expression in E14 mouse ESCs before and after treatment with a low level of the HDAC inhibitor valproic acid, we show that H3K9ac is enriched at gene promoters and is highly correlated with gene expression and with ..
  29. ncbi Synergistic neuroprotective effects of lithium and valproic acid or other histone deacetylase inhibitors in neurons: roles of glycogen synthase kinase-3 inhibition
    Yan Leng
    Molecular Neurobiology Section, Mood and Anxiety Disorders Program, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892 1363, USA
    J Neurosci 28:2576-88. 2008
    Lithium and valproic acid (VPA) are two primary drugs used to treat bipolar mood disorder and have frequently been used in combination to treat bipolar patients resistant to monotherapy with either drug...
  30. ncbi Safety and clinical activity of the combination of 5-azacytidine, valproic acid, and all-trans retinoic acid in acute myeloid leukemia and myelodysplastic syndrome
    Andres O Soriano
    Department of Leukemia, University of Texas M D Anderson Cancer Center, Houston, TX 77030, USA
    Blood 110:2302-8. 2007
    ..We conducted a phase 1/2 study of the combination of 5-azacitidine (5-AZA), valproic acid (VPA), and ATRA in patients with acute myeloid leukemia or high-risk myelodysplastic syndrome...
  31. ncbi Hyperconnectivity of local neocortical microcircuitry induced by prenatal exposure to valproic acid
    Tania Rinaldi
    Laboratory of Neural Microcircuitry, Brain Mind Institute, Ecole Polytechnique Federale de Lausanne, Lausanne 1015, Switzerland
    Cereb Cortex 18:763-70. 2008
    Exposure to valproic acid (VPA) during embryogenesis can cause several teratogenic effects, including developmental delays and in particular autism in humans if exposure occurs during the third week of gestation...
  32. ncbi Valproic acid reduces brain damage induced by transient focal cerebral ischemia in rats: potential roles of histone deacetylase inhibition and heat shock protein induction
    Ming Ren
    Molecular Neurobiology Section, National Institute of Mental Health, National Institutes of Health, 10 Center Drive, MSC 1363, Bethesda, MD 20892 1363, USA
    J Neurochem 89:1358-67. 2004
    Growing evidence from in vitro studies supports that valproic acid (VPA), an anti-convulsant and mood-stabilizing drug, has neuroprotective effects...
  33. ncbi Valproate: a reappraisal of its pharmacodynamic properties and mechanisms of action
    W Loscher
    Department of Pharmacology, Toxicology and Pharmacy, School of Veterinary Medicine, Hannover, Germany
    Prog Neurobiol 58:31-59. 1999
    ..By the experimental observations summarized in this review, most clinical effects of valproate can be explained, although much remains to be learned at a number of different levels of valproate's mechanisms of action...
  34. ncbi The mood stabilizers lithium and valproate selectively activate the promoter IV of brain-derived neurotrophic factor in neurons
    S Yasuda
    Molecular Neurobiology Section, Mood and Anxiety Disorders Program, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892 1363, USA
    Mol Psychiatry 14:51-9. 2009
    ..Lithium and valproic acid (VPA) are two primary mood-stabilizing drugs used to treat bipolar disorder...
  35. pmc Phase 2 clinical trial of 5-azacitidine, valproic acid, and all-trans retinoic acid in patients with high-risk acute myeloid leukemia or myelodysplastic syndrome
    Emmanuel Raffoux
    Departement d Hematologie, Hopital Saint Louis, Assistance Publique Hopitaux de Paris, and Université Denis Diderot Paris 7, EA 3518, Institut Universitaire d Hematologie, Paris
    Oncotarget 1:34-42. 2010
    In this Phase 2 study, we evaluated the efficacy of combination of 5-azacitidine (AZA), valproic acid (VPA), and all-trans retinoic acid (ATRA) in patients with high-risk acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS)...
  36. ncbi Effect of D-cycloserine and valproic acid on the extinction of reinstated fear-conditioned responses and habituation of fear conditioning in healthy humans: a randomized controlled trial
    Kenichi Kuriyama
    Department of Adult Mental Health, National Institute of Mental Health, National Center of Neurology and Psychiatry, 4 1 1 Ogawa Higashi, Kodaira, Tokyo 187 8502, Japan
    Psychopharmacology (Berl) 218:589-97. 2011
    Although the effects of D: -cycloserine (DCS) and valproic acid (VPA) on the facilitation of the extinction of fear-conditioned memory have been elucidated in animals, these effects have not been clearly confirmed in humans.
  37. ncbi Histone deacetylase is a target of valproic acid-mediated cellular differentiation
    Nadia Gurvich
    Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
    Cancer Res 64:1079-86. 2004
    b>Valproic acid (VPA), a well-established therapy for seizures and bipolar disorder, has recently been shown to inhibit histone deacetylases (HDACs)...
  38. pmc Valproic acid without intensified antiviral therapy has limited impact on persistent HIV infection of resting CD4+ T cells
    Nancy M Archin
    University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
    AIDS 22:1131-5. 2008
    b>Valproic acid and intensified antiretroviral therapy may deplete resting CD4+ T-cell HIV infection. We tested the ability of valproic acid to deplete resting CD4+ T-cell infection in patients receiving standard antiretroviral therapy.
  39. ncbi A common mechanism of action for three mood-stabilizing drugs
    Robin S B Williams
    Intracellular Signalling Group, MRC Laboratory for Molecular Cell Biology, University College London, Gower St, London WC1E 6BT, UK
    Nature 417:292-5. 2002
    Lithium, carbamazepine and valproic acid are effective mood-stabilizing treatments for bipolar affective disorder. The molecular mechanisms underlying the actions of these drugs and the illness itself are unknown...
  40. ncbi Valproic acid metabolism and its effects on mitochondrial fatty acid oxidation: a review
    M F B Silva
    Centro de Patogénese Molecular UBMBE, iMed UL, Faculdade de Farmacia da Universidade de Lisboa, Lisboa, Portugal
    J Inherit Metab Dis 31:205-16. 2008
    b>Valproic acid (VPA; 2-n-propylpentanoic acid) is widely used as a major drug in the treatment of epilepsy and in the control of several types of seizures...
  41. ncbi HDAC2 mediates therapeutic resistance of pancreatic cancer cells via the BH3-only protein NOXA
    P Fritsche
    Technische Universitat Munchen, Klinikum rechts der Isar, II Medizinische Klinik, Ismaninger Str 22, 81675 Munich, Germany
    Gut 58:1399-409. 2009
    ..Although histone deacetylase inhibitors (HDACi) are promising cancer therapeutics regulating proliferation, differentiation and apoptosis, molecular pathways engaged by specific HDAC isoenzymes in cancer are ill defined...
  42. pmc Resistance after chronic application of the HDAC-inhibitor valproic acid is associated with elevated Akt activation in renal cell carcinoma in vivo
    Eva Juengel
    Department of Urology, Johann Wolfgang Goethe University, Frankfurt am Main, Germany
    PLoS ONE 8:e53100. 2013
    ..study, the molecular mechanisms of acquired resistance towards the histone deacetylase (HDAC) inhibitor valproic acid (VPA) in a RCC in vivo model were investigated...
  43. pmc Valproic acid affects membrane trafficking and cell-wall integrity in fission yeast
    Makoto Miyatake
    Division of Molecular Pharmacology and Pharmacogenomics, Department of Genome Sciences, Kobe University Graduate School of Medicine, Kobe, Hyogo 650 0017, Japan
    Genetics 175:1695-705. 2007
    b>Valproic acid (VPA) is widely used to treat epilepsy and manic-depressive illness. Although VPA has been reported to exert a variety of biochemical effects, the exact mechanisms underlying its therapeutic effects remain elusive...
  44. ncbi Histone deacetylase inhibitors exhibit anti-inflammatory and neuroprotective effects in a rat permanent ischemic model of stroke: multiple mechanisms of action
    Hyeon Ju Kim
    Molecular Neurobiology Section, National Institute of Mental Health, National Institutes of Health, Building 10, Bethesda, MD 20892 1363, USA
    J Pharmacol Exp Ther 321:892-901. 2007
    ..We found that post-pMCAO injections with HDAC inhibitors, valproic acid (VPA), sodium butyrate (SB), or trichostatin A (TSA), decreased brain infarct volume...
  45. ncbi Phase I study of 5-aza-2'-deoxycytidine in combination with valproic acid in non-small-cell lung cancer
    B F Chu
    Division of Medical Oncology, Department of Medicine, College of Medicine and Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA
    Cancer Chemother Pharmacol 71:115-21. 2013
    ..The development of epigenetic-modulating agents utilizing the synergism between hypomethylating agents and histone deacetylase (HDAC) inhibitors provides a novel therapeutic approach in treating NSCLC...
  46. ncbi Hippocampal synaptic plasticity, memory, and epilepsy: effects of long-term valproic acid treatment
    Carmelo Sgobio
    Fondazione Santa Lucia, Istituto di Ricovero e Cura a Carattere Scientifico, Rome, Italy
    Biol Psychiatry 67:567-74. 2010
    ..to investigate hippocampal synaptic plasticity and morphology as well as hippocampal-dependent memory in physiologic conditions and in a genetic model of epilepsy following chronic treatment with the widely used AED valproic acid (VPA).
  47. pmc Ethosuximide, valproic acid, and lamotrigine in childhood absence epilepsy
    Tracy A Glauser
    Comprehensive Epilepsy Center, Division of Neurology, Cincinnati Children s Hospital, 3333 Burnet Ave, MLC 2015, Cincinnati, OH 45229, USA
    N Engl J Med 362:790-9. 2010
    Childhood absence epilepsy, the most common pediatric epilepsy syndrome, is usually treated with ethosuximide, valproic acid, or lamotrigine. The most efficacious and tolerable initial empirical treatment has not been defined.
  48. ncbi Antileukemic activity of valproic acid in chronic lymphocytic leukemia B cells defined by microarray analysis
    B Stamatopoulos
    Laboratory of Experimental Hematology, Faculty of Medicine, Institut Jules Bordet, Universite Libre de Bruxelles, Boulevard de Waterloo 121, Brussels, Belgium
    Leukemia 23:2281-9. 2009
    ..In this study, we analyzed gene expression modifications in CLL B cells after treatment with valproic acid (VPA), a well-tolerated anti-epileptic drug with HDAC inhibitory activity...
  49. ncbi Behavioral and molecular changes in the mouse in response to prenatal exposure to the anti-epileptic drug valproic acid
    F I Roullet
    Department of Psychiatry and Behavioural Neurosciences, McMaster University, St Joseph s Healthcare, 50 Charlton Avenue East, Hamilton, ON, L8N 4A6 Canada
    Neuroscience 170:514-22. 2010
    Experiments in rodents have indicated that maternal valproic acid (VPA) exposure has permanent adverse effects upon neurological and behavioral development...
  50. ncbi Antitumor effects of a combined 5-aza-2'deoxycytidine and valproic acid treatment on rhabdomyosarcoma and medulloblastoma in Ptch mutant mice
    Ines Ecke
    Institute of Human Genetics, University of Goettingen, Gottingen, Germany
    Cancer Res 69:887-95. 2009
    ..with the Dnmt inhibitor 5-aza-2'deoxycytidine (5-aza-dC) and the histone deacetlyase (HDAC) inhibitor valproic acid (VPA) efficiently prevented MB and RMS formation, whereas monotherapies with either drug were less effective...
  51. ncbi Teratogenic effects mediated by inhibition of histone deacetylases: evidence from quantitative structure activity relationships of 20 valproic acid derivatives
    Daniel Eikel
    Department of Food Toxicology and Chemical Analysis Food Toxicology, Center for Systemic Neuroscience Hannover, University of Veterinary Medicine Hannover, Foundation, Bischofsholer Damm 15, D 30173 Hannover, Germany
    Chem Res Toxicol 19:272-8. 2006
    The widely used antiepileptic drug valproic acid (VPA), which is also used in migraine prophylaxis and the treatment of bipolar disorders, is also under trial as an anticancer agent...
  52. ncbi Quantifying in vivo phosphoinositide turnover in chemotactically competent Dictyostelium cells
    Nadine Pawolleck
    Bourne Laboratory, Biomedical Sciences Division, School of Biological Sciences, Royal Holloway University of London, Egham, Surrey, UK
    Methods Mol Biol 571:283-90. 2009
    ..acute reduction of PI phosphorylation in response to a widely used bipolar disorder and epilepsy treatment, valproic acid, as a potential therapeutic role for the drug using chemotactically competent Dictyostelium...
  53. ncbi Structure-function studies for the panacea, valproic acid
    Nicole Terbach
    Centre for Biomedical Sciences, School of Biological Sciences, Royal Holloway University of London, Egham, UK
    Biochem Soc Trans 37:1126-32. 2009
    The anticonvulsant properties of VPA (valproic acid), a branched short-chain fatty acid, were serendipitously discovered in 1963...
  54. pmc Antiretroviral intensification and valproic acid lack sustained effect on residual HIV-1 viremia or resting CD4+ cell infection
    Nancie M Archin
    University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America
    PLoS ONE 5:e9390. 2010
    ..evidence that resting CD4+ T cell infection (RCI) is affected by the histone deacetylase (HDAC) inhibitor valproic acid (VPA), we measured the stability of RCI and residual viremia in patients who added VPA with or without ..
  55. ncbi Prevention of hypoxia-induced neuronal apoptosis through histone deacetylase inhibition
    Yongqing Li
    Department of Surgery, Division of Trauma, Emergency Surgery and Surgical Critical Care, Massachusetts General Hospital Harvard Medical School, Boston, Massachusetts, USA
    J Trauma 64:863-70; discussion 870-1. 2008
    We have recently discovered that administration of valproic acid (VPA), a histone deacetylase inhibitor, enhances nuclear histone acetylation and improves survival after lethal hemorrhage in rats...
  56. ncbi Chronic administration of valproic acid inhibits activation of mouse hepatic stellate cells in vitro and in vivo
    Inge Mannaerts
    Department of Cell Biology, Vrije Universiteit Brussel, Brussels, Belgium
    Hepatology 51:603-14. 2010
    ..We analyzed the effect of a histone deacetylase inhibitor, valproic acid (VPA), on mouse HSC transdifferentiation in vitro and in vivo...
  57. pmc Valproic acid attenuates blood-brain barrier disruption in a rat model of transient focal cerebral ischemia: the roles of HDAC and MMP-9 inhibition
    Zhifei Wang
    Molecular Neurobiology Section, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892 1363, USA
    J Cereb Blood Flow Metab 31:52-7. 2011
    b>Valproic acid (VPA), a histone deacetylase (HDAC) inhibitor, is known to protect against cerebral ischemia...
  58. ncbi Lithium and valproic acid: parallels and contrasts in diverse signaling contexts
    Nadia Gurvich
    Graduate Group in Pharmacological Sciences, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Pharmacol Ther 96:45-66. 2002
    ..b>Valproic acid (VPA), a widely used anticonvulsant, is also an effective therapy for BPD, and again its mechanism of action ..
  59. ncbi Valproic acid increases the SMN2 protein level: a well-known drug as a potential therapy for spinal muscular atrophy
    L Brichta
    Institute of Human Genetics, University of Bonn, Wilhelmstrasse 31, 53111 Bonn, Germany
    Hum Mol Genet 12:2481-9. 2003
    ..5-500 microM) of valproic acid (VPA), the level of full-length SMN2 mRNA/protein increased 2- to 4-fold...
  60. ncbi Valproic acid, a mood stabilizer and anticonvulsant, protects rat cerebral cortical neurons from spontaneous cell death: a role of histone deacetylase inhibition
    Mi Ra Jeong
    Molecular Neurobiology Section, National Institute of Mental Health, National Institutes of Health, Bldg 10, Rm 4C 206, 10 Center Dr MSC 1363, Bethesda, MD 20892 1363, USA
    FEBS Lett 542:74-8. 2003
    We studied the neuroprotective effects of valproic acid (VPA), a primary mood stabilizer and anticonvulsant, in cultured rat cerebral cortical neurons (CCNs). CCNs underwent spontaneous cell death when their age increased in culture...
  61. ncbi Mood stabilizer valproate promotes ERK pathway-dependent cortical neuronal growth and neurogenesis
    Yanlei Hao
    Laboratory of Molecular Pathophysiology, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892 4405, USA
    J Neurosci 24:6590-9. 2004
    ..This cascade of events provides a potential mechanism whereby mood stabilizers alleviate cerebral morphometric deficits associated with manic-depressive illness...
  62. ncbi Sodium valproate: an old drug with new roles
    Natalia N Nalivaeva
    Institute of Molecular and Cellular Biology, University of Leeds, Leeds LS2 9JT, UK
    Trends Pharmacol Sci 30:509-14. 2009
    ..This article reviews the pharmacology of this remarkable molecule, focusing on its actions as a neuroprotectant and hence with new potential in the treatment of neurodegenerative diseases...
  63. pmc Valproic acid and other histone deacetylase inhibitors induce microglial apoptosis and attenuate lipopolysaccharide-induced dopaminergic neurotoxicity
    P S Chen
    Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA
    Neuroscience 149:203-12. 2007
    b>Valproic acid (VPA), a widely prescribed drug for seizures and bipolar disorder, has been shown to be an inhibitor of histone deacetylase (HDAC)...
  64. ncbi The mood-stabilizing agents lithium and valproate robustly increase the levels of the neuroprotective protein bcl-2 in the CNS
    G Chen
    Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, Michigan 48201, USA
    J Neurochem 72:879-82. 1999
    ..These novel findings represent the first report of medication-induced increases in CNS bcl-2 levels and may have implications not only for mood disorders, but also for long-term treatment of various neurodegenerative disorders...
  65. ncbi Valproic acid is neuroprotective in the rotenone rat model of Parkinson's disease: involvement of alpha-synuclein
    Barbara Monti
    Department of Biology, University of Bologna, Bologna, Italy
    Neurotox Res 17:130-41. 2010
    b>Valproic acid (VPA), an established antiepileptic and antimanic drug, has recently emerged as a promising neuroprotective agent...
  66. ncbi Valproic acid induces growth arrest, apoptosis, and senescence in medulloblastomas by increasing histone hyperacetylation and regulating expression of p21Cip1, CDK4, and CMYC
    Xiao Nan Li
    Laboratory of Molecular Neurooncology, Texas Children s Hospital, Baylor College of Medicine, Houston, TX 77030, USA
    Mol Cancer Ther 4:1912-22. 2005
    b>Valproic acid is a well-tolerated anticonvulsant that has been identified recently as a histone deacetylase inhibitor...
  67. ncbi Valproate may improve strength and function in patients with type III/IV spinal muscle atrophy
    Conrad C Weihl
    Department of Neurology, Washington University School of Medicine, 660 South Euclid Avenue, Box 8111, St Louis, MO 63110, USA
    Neurology 67:500-1. 2006
    ..The treated patients with SMA had increased quantitative muscle strength and subjective function. Further trials of valproate treatment for SMA type III/IV are warranted...
  68. pmc Phase II open label study of valproic acid in spinal muscular atrophy
    Kathryn J Swoboda
    Departments of Neurology, Pediatrics, Neonatology and General Clinical Research Center, University of Utah School of Medicine, Salt Lake City, Utah, United States of America
    PLoS ONE 4:e5268. 2009
    Preliminary in vitro and in vivo studies with valproic acid (VPA) in cell lines and patients with spinal muscular atrophy (SMA) demonstrate increased expression of SMN, supporting the possibility of therapeutic benefit...
  69. pmc Phase I study of epigenetic modulation with 5-azacytidine and valproic acid in patients with advanced cancers
    Fadi Braiteh
    Department of Investigational Cancer Therapeutics Phase I Program, Division of Cancer Medicine and Quantitative Sciences, University of Texas M D Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA
    Clin Cancer Res 14:6296-301. 2008
    5-Azacytidine (5-AZA) is a DNA-hypomethylating agent. Valproic acid is a histone deacetylase inhibitor. Combining hypomethylating agents and histone deacetylase inhibitors produces synergistic anticancer activity in vitro and in vivo...
  70. ncbi Valproic acid increases SMN levels in spinal muscular atrophy patient cells
    Charlotte J Sumner
    Neurogenetics Branch, National Institute of Neurologic Diseases and Stroke NIH, Building 10, Room 3B 14, MSC 1250, 10 Center Drive, Bethesda, MD 20892, USA
    Ann Neurol 54:647-54. 2003
    ..Here, we show that valproic acid increases levels of exon 7-containing SMN transcript and SMN protein in type I SMA patient-derived fibroblast ..
  71. pmc Valproic acid induces hair regeneration in murine model and activates alkaline phosphatase activity in human dermal papilla cells
    Soung Hoon Lee
    Translational Research Center for Protein Function Control, Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, South Korea
    PLoS ONE 7:e34152. 2012
    ..We have identified a new function for valproic acid (VPA), a GSK3β inhibitor that activates the Wnt/β-catenin pathway, to promote hair re-growth in vitro and in ..
  72. ncbi HDAC inhibition delays cell cycle progression of human bladder cancer cells in vitro
    Stefan Vallo
    Department of Urology, Johann Wolfgang Goethe University, Frankfurt am Main, Germany
    Anticancer Drugs 22:1002-9. 2011
    Our aim was to analyze the impact of the histone deacetylase (HDAC)-inhibitor valproic acid (VPA) on bladder cancer cell growth in vitro. RT-4, TCCSUP, UMUC-3, and RT-112 bladder cancer cells were treated with VPA (0...
  73. ncbi Neuroconnectivity and valproic acid: the myelin hypothesis
    Ivana Rosenzweig
    Academic Unit of Sleep and Department of Psychiatry, Royal Brompton Hospital, London, UK
    Neurosci Biobehav Rev 36:1848-56. 2012
    Neuropsychiatric medications that directly alter the epigenome, such as valproic acid, can under certain conditions reactivate critical developmental periods and thus impact adult neuroconnectivity...
  74. ncbi Valproate corrects the schizophrenia-like epigenetic behavioral modifications induced by methionine in mice
    Lucio Tremolizzo
    Department of Psychiatry, Psychiatric Institute, College of Medicine, University of Illinois at Chicago, Illinois 60612, USA
    Biol Psychiatry 57:500-9. 2005
    ..We studied whether MET-induced epigenetic reelin promoter hypermethylation and the associated behavioral alterations can be reduced by valproate in doses that inhibit histone deacetylases (HDACs)...
  75. pmc In vitro evaluation of valproic acid as an inhibitor of human cytochrome P450 isoforms: preferential inhibition of cytochrome P450 2C9 (CYP2C9)
    X Wen
    Department of Clinical Pharmacology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland
    Br J Clin Pharmacol 52:547-53. 2001
    AIMS: To evaluate the potency and specificity of valproic acid as an inhibitor of the activity of different human CYP isoforms in liver microsomes...
  76. pmc Role of histone acetylation in the stimulatory effect of valproic acid on vascular endothelial tissue-type plasminogen activator expression
    Pia Larsson
    The Wallenberg Laboratory for Cardiovascular Research, Institute of Medicine, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
    PLoS ONE 7:e31573. 2012
    ..We investigated if the anti-epileptic drug valproic acid (VPA) is capable of enhancing t-PA expression in vitro in vascular endothelial cells, and further examined if ..
  77. pmc SMA CARNIVAL TRIAL PART II: a prospective, single-armed trial of L-carnitine and valproic acid in ambulatory children with spinal muscular atrophy
    John T Kissel
    Department of Neurology, The Ohio State University, Columbus, Ohio, United States of America
    PLoS ONE 6:e21296. 2011
    Multiple lines of evidence have suggested that valproic acid (VPA) might benefit patients with spinal muscular atrophy (SMA). The SMA CARNIVAL TRIAL was a two part prospective trial to evaluate oral VPA and L-carnitine in SMA children...
  78. pmc Valproic acid inhibits Abeta production, neuritic plaque formation, and behavioral deficits in Alzheimer's disease mouse models
    Hong Qing
    Department of Psychiatry, Townsend Family Laboratories, Brain Research Center, University of British Columbia, Vancouver, BC, Canada
    J Exp Med 205:2781-9. 2008
    ..b>Valproic acid (VPA) is one of the most widely used anticonvulsant and mood-stabilizing agents for treating epilepsy and ..
  79. pmc Effect of valproic acid on acute lung injury in a rodent model of intestinal ischemia reperfusion
    Kyuseok Kim
    Department of Surgery, Division of Trauma, Emergency Surgery and Surgical Critical Care, Massachusetts General Hospital Harvard Medical School, Boston, MA, USA
    Resuscitation 83:243-8. 2012
    ..b>Valproic acid (VPA), a well-known anti-epileptic drug, has been shown to have anti-oxidant and anti-inflammatory effects in ..
  80. ncbi Histone deacetylase inhibitors augment antitumor efficacy of herpes-based oncolytic viruses
    Akihiro Otsuki
    Dardinger Laboratory for Neuro oncology and Neurosciences, Department of Neurological Surgery, The Ohio State University Medical Center and James Comprehensive Cancer Center, Columbus, Ohio, 43210 USA
    Mol Ther 16:1546-55. 2008
    ..b>Valproic acid (VPA), a commonly used antiepileptic agent with HDAC inhibitory activity, proved most effective when used to ..
  81. pmc Protective effects of valproic acid on the nigrostriatal dopamine system in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson's disease
    S K Kidd
    Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, 1020 Locust Street, JAH 521, Philadelphia, PA 19107, USA
    Neuroscience 194:189-94. 2011
    ..The present study was conducted to extend these findings to an in vivo PD model. The HDACi valproic acid (VPA) was co-administered with MPTP for 5 days to male FVBn mice and continued for an additional 2 weeks, ..
  82. ncbi Valproic acid is not a substrate for P-glycoprotein or multidrug resistance proteins 1 and 2 in a number of in vitro and in vivo transport assays
    Steffen Baltes
    Department of Pharmacology, Toxicology, and Pharmacy, University of Veterinary Medicine, Bunteweg 17, D 30559 Hannover, Germany
    J Pharmacol Exp Ther 320:331-43. 2007
    The antiepileptic drug valproic acid (VPA) is widely used in the treatment of epilepsy, bipolar disorders, and migraine...
  83. ncbi Anti-tumor mechanisms of valproate: a novel role for an old drug
    Roman A Blaheta
    Zentrum der Hygiene, Institut fur Medizinische Virologie, Interdisziplinäres Labor für Tumor und Virus for schung, Klinikum der J W Goethe Universitat, Frankfurt am Main, Germany
    Med Res Rev 22:492-511. 2002
    b>Valproic acid (VPA, 2-propylpentanoic acid) is an established drug in the long-term therapy of epilepsy. During the past years, it has become evident that VPA is also associated with anti-cancer activity...
  84. pmc Brain delivery of valproic acid via intranasal administration of nanostructured lipid carriers: in vivo pharmacodynamic studies using rat electroshock model
    Sharareh Eskandari
    Department of Pharmaceutics, School of Pharmacy and Isfahan Pharmaceutical Sciences Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
    Int J Nanomedicine 6:363-71. 2011
    ..The objective of this study was delivery of valproic acid (VPA) to the brain by intranasal route...
  85. pmc Antiplatelet activity of valproic acid contributes to decreased soluble CD40 ligand production in HIV type 1-infected individuals
    Donna C Davidson
    Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA
    J Immunol 186:584-91. 2011
    ..In this study, we demonstrate that the mood-stabilizing drug valproic acid (VPA) reduces sCD40L levels in plasma samples of HIV-1-infected patients (n = 23) and in washed human ..
  86. ncbi Valproic acid but not D-cycloserine facilitates sleep-dependent offline learning of extinction and habituation of conditioned fear in humans
    Kenichi Kuriyama
    Department of Adult Mental Health, National Institute of Mental Health, National Center of Neurology and Psychiatry, 4 1 1 Ogawa Higashi, Kodaira, Tokyo 187 8502, Japan
    Neuropharmacology 64:424-31. 2013
    The effectiveness of D-cycloserine (DCS), an N-methyl-D-aspartate glutamate receptor partial agonist, and valproic acid (VPA), a histone deacetylase inhibitor, in facilitating the extinction of fear-conditioned memory has been explored ..
  87. pmc Deep brain stimulation, histone deacetylase inhibitors and glutamatergic drugs rescue resistance to fear extinction in a genetic mouse model
    Nigel Whittle
    Department of Pharmacology and Toxicology, Institute of Pharmacy and Center for Molecular Biosciences Innsbruck CMBI, University of Innsbruck, Innrain 80 82 III, A 6020 Innsbruck, Austria
    Neuropharmacology 64:414-23. 2013
    ..and deficient extinction consolidation/retrieval was achieved with prior extinction training administration of valproic acid (a GABAergic enhancer and HDAC inhibitor) or AMN082 [metabotropic glutamate receptor 7 (mGlu7) agonist], while ..
  88. ncbi Valproic acid induces microglial dysfunction, not apoptosis, in human glial cultures
    Hannah M Gibbons
    Department of Pharmacology and Clinical Pharmacology, The University of Auckland, Auckland, New Zealand
    Neurobiol Dis 41:96-103. 2011
    b>Valproic acid (VPA) is widely used for the treatment of mood disorders and epilepsy, but its mechanism of action is unclear...
  89. pmc Low-dose valproic acid enhances radiosensitivity of prostate cancer through acetylated p53-dependent modulation of mitochondrial membrane potential and apoptosis
    Xufeng Chen
    Department of Radiation Oncology, City of Hope National Medical Center and Beckman Research Institute, Duarte, California 91010, USA
    Mol Cancer Res 9:448-61. 2011
    ..In this study, we show in prostate cancer cells that valproic acid (VPA) at low concentrations has minimal cytotoxic effects yet can significantly increase radiation-induced ..
  90. pmc mGluR5-antagonist mediated reversal of elevated stereotyped, repetitive behaviors in the VPA model of autism
    Mili V Mehta
    Translational Neuroscience Program, Department of Psychiatry, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America
    PLoS ONE 6:e26077. 2011
    ..MPEP), an mGluR5-receptor antagonist, on repetitive and anxiety-like behaviors in the valproic acid (VPA) mouse model of autism...
  91. ncbi Prenatal exposure to valproic acid leads to reduced expression of synaptic adhesion molecule neuroligin 3 in mice
    E Kolozsi
    Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, Ontario, Canada
    Neuroscience 163:1201-10. 2009
    In rodents, a single administration of valproic acid (VPA) in utero leads to developmental delays and lifelong deficits in motor performance, social behavior, and anxiety-like behavior in the offspring...
  92. ncbi Valproic acid enhances bosutinib cytotoxicity in colon cancer cells
    Luca Mologni
    Department of Clinical Medicine and Prevention, University of Milano Bicocca, Monza, Italy
    Int J Cancer 124:1990-6. 2009
    ..Inhibition of HDAC activity is often associated with cancer cell growth impairment and death. Valproic acid (VPA) is a HDAC inhibitor used for the treatment of epilepsy...
  93. ncbi Valproic acid perturbs hematopoietic homeostasis by inhibition of erythroid differentiation and activation of the myelo-monocytic pathway
    Sebastien Chateauvieux
    Laboratoire de Biologie Moléculaire et Cellulaire du Cancer, Hopital Kirchberg, L 2540 Luxembourg, Luxembourg
    Biochem Pharmacol 81:498-509. 2011
    As a histone deacetylase inhibitor, valproic acid (VPA) is a candidate for anticancer therapy. Besides, VPA exhibits various mechanisms of action and its effects on the molecular basis of hematopoiesis remain unclear...
  94. ncbi Combination of the histone deacetylase inhibitor valproic acid with oral hydroxyurea or 6-mercaptopurin can be safe and effective in patients with advanced acute myeloid leukaemia--a report of five cases
    Hanne Fredly
    Section for Hematology, Institute of Medicine and Dentistry, University of Bergen, Bergen, Norway
    Hematology 15:338-43. 2010
    Disease-stabilizing therapy with the histone deacetylase inhibitor valproic acid and all-trans retinoic acid (ATRA) has been investigated in acute myelogenous leukemia (AML) in a number of trials...
  95. ncbi Valproic acid increases formation of reactive oxygen species and induces apoptosis in postimplantation embryos: a role for oxidative stress in valproic acid-induced neural tube defects
    Emily W Y Tung
    Department of Biomedical and Molecular Sciences, Graduate Program in Pharmacology and Toxicology, Queen s University, Kingston, Ontario, Canada
    Mol Pharmacol 80:979-87. 2011
    Exposure to the anticonvulsant valproic acid (VPA) during the first trimester of pregnancy is associated with an increased risk of congenital malformations including heart defects, craniofacial abnormalities, skeletal and limb defects, ..
  96. ncbi Antitumor activities of valproic acid on Epstein-Barr virus-associated T and natural killer lymphoma cells
    Seiko Iwata
    Departments of Virology Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan
    Cancer Sci 103:375-81. 2012
    ..In the present study, we evaluated the killing effect of valproic acid (VPA), which acts as an HDAC inhibitor, on EBV-positive and -negative T and NK lymphoma cells...
  97. ncbi Valproate attenuates the risk of myocardial infarction in patients with epilepsy: a nationwide cohort study
    Jonas Bjerring Olesen
    Department of Cardiology, Gentofte University Hospital, Hellerup, Denmark
    Pharmacoepidemiol Drug Saf 20:146-53. 2011
    ..Patients with epilepsy have increased risk of myocardial infarction (MI). Valproate can exert anti-atherosclerotic effects. We therefore examined the risk of MI in patients with epilepsy receiving valproate...
  98. ncbi The histone deacetylase inhibitor valproic acid alters growth properties of renal cell carcinoma in vitro and in vivo
    Jon Jones
    Department of Urology and Pediatric Urology, Goethe University, Frankfurt am Main, Germany
    J Cell Mol Med 13:2376-85. 2009
    ..The effects of the HDAC inhibitor valproic acid (VPA) were tested in vitro and in vivo on pre-clinical renal cell carcinoma (RCC) models...
  99. ncbi Synaptic and intrinsic balancing during postnatal development in rat pups exposed to valproic acid in utero
    Elisabeth C Walcott
    The Neurosciences Institute, San Diego, California 92121, USA
    J Neurosci 31:13097-109. 2011
    b>Valproic acid (VPA) is among the most teratogenic of commonly prescribed anticonvulsants, increasing the risk in humans of major malformations and impaired cognitive development...
  100. pmc The antiepileptic drug valproic acid and other medium-chain fatty acids acutely reduce phosphoinositide levels independently of inositol in Dictyostelium
    Pishan Chang
    Centre for Biomedical Sciences, School of Biological Sciences, Royal Holloway University of London, Egham, TW20 0EX, UK
    Dis Model Mech 5:115-24. 2012
    b>Valproic acid (VPA) is the most widely prescribed epilepsy treatment worldwide, but its mechanism of action remains unclear...
  101. ncbi Gadd45a, the gene induced by the mood stabilizer valproic acid, regulates neurite outgrowth through JNK and the substrate paxillin in N1E-115 neuroblastoma cells
    Junji Yamauchi
    Department of Pharmacology, National Research Institute for Child Health and Development, 2 10 1 Oukura, Setagaya, Tokyo 157 8535, Japan
    Exp Cell Res 313:1886-96. 2007
    b>Valproic acid (VPA), a mood stabilizer and anticonvulsant, has a variety of neurotrophic functions; however, less is known about how VPA regulates neurite outgrowth...

Research Grants65

  1. COMMON POLYMORPHISM EFFECTS ON UREA CYCLE FUNCTION
    Marshall Summar; Fiscal Year: 2001
    ..A common example is the frequent hyperammonemia observed in patients following administration of the drug valproic acid. With the increase in bone marrow transplant procedures (BMT), a number of hyperammonemic deaths have been ..
  2. MOLECULAR TARGETS OF LITHIUM AND VALPROATE
    MIRIAM GREENBERG; Fiscal Year: 2004
    ..The yeast model system may also be utilized in future testing of safer and more effective treatments. ..
  3. MAGNESIUM SULFATE FOR NEUROPROTECTION AFTER BRAIN TRAUMA
    Nancy Temkin; Fiscal Year: 2004
    ..abstract_text> ..
  4. Patient-Derived Stem Cells for Phosphoproteomic Profiling Neuropsychopathology
    Dieter A Wolf; Fiscal Year: 2011
    ..has been the standard of treatment for BPD, but, because of its side effects, anti-convulsants (including valproic acid, lamotrigine, topiramate &carbamazepine) &atypical anti-psychotics have also been prescribed...
  5. Therapeutic Approaches for Extinction of Conditioned Drug Reward
    Gary B Kaplan; Fiscal Year: 2013
    ..This proposal examines new treatment approaches using pharmacological and behavioral treatments to extinguish cue reactivity in an animal model. Such approaches can inform future clinical trials for opiate abusing veterans. ..
  6. Epigenetic downregulation of the antibody response and inhibition of autoimmunity
    Paolo Casali; Fiscal Year: 2013
    ..We will analyze the impact of HDIs (valproic acid, butyrate, suberoylanilide hydroxamic acid) on T-dependent and T-independent antibody responses in normal ..
  7. Estradiol-Induced Sialyation Of NCAM Prevents Leucocyte:Endothelial Adhesion
    Frederick Naftolin; Fiscal Year: 2010
    ..We will compare the results with effects of the Ras pathway inducer valproic acid which is known to induce PSA-NCAM...
  8. Aging and Antipsychotic Efficacy - Epigenetic Mechanisms
    Hongxin Dong; Fiscal Year: 2013
    ..Co-treatment with valproic acid (VPA), a histone deacetylase HDAC inhibitor, was shown to restore antipsychotic induced c-Fos induction and ..
  9. Reprogramming of endothelial cells for improved cardiomyogenicity in vivo
    MELISSA ANN THAL; Fiscal Year: 2012
    ..Epigenetic reprogramming using chemical modifiers of DNA methylation (5-Azacytidine) and histone acetylation (valproic acid) have been shown to change the trans-differentiation capabilities of a given cell...
  10. Relationship between Hdac3 suppression and Wnt signaling in osteoblasts
    Meghan McGee-Lawrence; Fiscal Year: 2011
    ..g., ZolinzaTM, Valproate, used clinically as anti-cancer and anti-epileptic therapies) affect the skeleton. ..
  11. Excitotoxicity in Circulatory Arrest ? Brain Injury
    WILLIAM ANTHONY BAUMGARTNER; Fiscal Year: 2012
    ..To identify neuroprotective changes in gene expression that result from a novel therapeutic strategy (Valproic acid) and 3...
  12. Multigenerational FamIlial and Environmental Risk for Autism (MINERvA) Network
    Abraham Reichenberg; Fiscal Year: 2013
    ....
  13. Mechanisms of Valproic Acid-Induced Neurodevelopmental and Behavioral Defects
    Elizabeth M Powell; Fiscal Year: 2013
    ..b>Valproic acid (VPA) is an antiepileptic and mood stabilizing drug that, when administered during pregnancy, causes ..
  14. Effects of short-chain fatty acids on Epstein-Barr virus in B cell lymphoma
    Kelly L Gorres; Fiscal Year: 2013
    ..Another SCFA and HDAC inhibitor, valproic acid (VPA), does not reactivate EBV. In fact, VPA blocks viral reactivation by butyrate...
  15. microRNAs in Developmental Toxicology
    Mark E Hahn; Fiscal Year: 2010
    ..of Aim 1 and perform microRNA profiling in zebrafish embryos exposed to the known human teratogens ethanol, valproic acid, and retinoic acid...
  16. Validation of High-Throughput Screening of Candidate Antiepileptogenic Drugs
    Andrey Mazarati; Fiscal Year: 2009
    ..The current project is designed to introduce and validate an animal model of epileptogenesis that would allow for the quick and effective screening of emerging antiepileptogenic drugs on a large scale. ..
  17. The Effect of Bipolar Disorder and its Comorbidities on Cognition in Older Adults
    ARIEL GERARD GILDENGERS; Fiscal Year: 2013
    ..The knowledge gained from this research may benefit not only patients with Bipolar Disorder, but the broader population of older adults at high risk for disorders associated with neurodegeneration and premature cognitive decline. ..
  18. Optimization of the FPI model for epilepsy therapy development
    RAIMONDO D'AMBROSIO; Fiscal Year: 2013
    ....
  19. Rational polytherapy in the treatment of cholinergic seizures
    Claude G Wasterlain; Fiscal Year: 2013
    ....
  20. Design and synthesis of novel anticonvulsant molecules.
    Rajesh Kumar Mishra; Fiscal Year: 2011
    ..MB003), both exhibit lower ED50s than many other anti-convulsant drugs including valproic acid, felbamate, carbamazepine, phenytoin, and ethosuximide...
  21. Clavulanic acid: a potential abuse-deterrent and CNS-active therapeutic
    Scott M Rawls; Fiscal Year: 2012
    ..Utilization of this proven strategy here may identify a novel CNS-active therapeutic, in much the same way that valproic acid is used to manage prostate cancer and NSAIDs are used to manage Alzheimer's disease.
  22. Mood-Stabilizing Medications and the Inositol Signaling System
    Ranga N Parthasarathy; Fiscal Year: 2013
    ..Thus advancing our understanding of the pathophysiology of BD and disclosing new therapeutic targets for treating BD. ..
  23. N-acetylglutamate Synthase: Structure, Function &Defects
    Mendel Tuchman; Fiscal Year: 2012
    ..This will lead to constructing a structural model of mammalian NAGS, deriving at a catalytic mechanism, determining the mechanism of arginine effect, and the effects of mutations causing NAGS dysfunction and hyperammonemia. ..
  24. HDAC inhibition for the chemoprevention of lung cancer
    Johann Christoph Brandes; Fiscal Year: 2013
    ..With a 37% absolute risk reduction for lung cancer incidence, this would translate into 55,000 lives saved per year. ..
  25. Epigenetic regulation of microRNAs in neurogenesis
    Ronald P Hart; Fiscal Year: 2010
    ..We will use "deep sequencing" of microRNAs and gene regulatory regions to identify novel neurogenesis mechanisms. ..
  26. The Effects of Antiepileptic Drugs on Serologic Indices of Vascular Risk
    Scott Mintzer; Fiscal Year: 2012
    ....
  27. Role of Gut Associated Lymphoid Tissue in HIV Persistence
    Joseph K Wong; Fiscal Year: 2011
    ..from patients on ART will be studied before and after addition of the Histone Deacetylase I (HDAC) inhibitor, valproic acid to determine whether there is differential induction of HIV transcription in GALT...
  28. Histone Deacetylase Inhibitors and Inflammatory Bowel Disease
    EDWIN FULCO DEZOETEN; Fiscal Year: 2012
    ....
  29. Genetic Regulation of Valproic Acid Teratogenicity
    Richard H Finnell; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): The in utero exposure to the pharmaceutical compound Depakene (Valproic Acid;VPA) increases the incidence of congenital malformations and neurodevelopmental defects in humans...
  30. The H3K9 HISTONE SWITCH;'LEVELS'IN SCHIZOPHRENIA BLOOD AND BRAIN
    RAJIV PANDIT SHARMA; Fiscal Year: 2013
    ..levels of the permissive state (AceH3K9) that will respond preferentially to a clinical HDAC inhibitor such as valproic acid. Chromatin structure and function will be examined in both, postmortem brain samples from the Harvard brain ..
  31. Specific killing of latently HIV-1-infected cells after provirus reactivation
    Qigui Yu; Fiscal Year: 2013
    ..Several stimulants including IL-7, valproic acid (VPA), suberoylanilide hydroxamic acid (SAHA) and prostratin have been explored to force activation of ..
  32. Randomized study of combined epigenetic therapy
    Jean Pierre J Issa; Fiscal Year: 2011
    ..We recently completed a phase I study combining DAC with valproic acid (VPA), an orally available HDACi, initially approved as an anti-seizure medication but that also has ..
  33. COCAINE-BINDING DOPAMINE TRANSPORTER: MOLECULAR BIOLOGY
    Michael J Bannon; Fiscal Year: 2012
    ....
  34. A Phase II/II Investigation of the Effect of Vorinostat (VOR) in HIV Infection
    David M Margolis; Fiscal Year: 2013
    ..Studies of the weak HDAC inhibitor valproic acid failed to measure a consistent depletion of resting cell infection in patients on ART, but this effect is far ..
  35. Pilot PET Study Characterizing [1-11C] Arachadonic Acid in Bipolar Disorder
    M Elizabeth Sublette; Fiscal Year: 2013
    ....
  36. Pharmacogenomics of Mood Stabilizer Response in Bipolar Disorder
    John R Kelsoe; Fiscal Year: 2013
    ..The primary outcome measure will be time to relapse. Patients who fail lithium will be crossed over to valproic acid, those failing both drugs will enter the treatment as usual arm...
  37. Animal Model of Speech Sound Processing in Autism
    Michael P Kilgard; Fiscal Year: 2013
    ..We propose to evaluate speech sound coding in the valproic acid (VPA) animal model of autism, and quantify the beneficial effects of two common autism therapies: auditory ..
  38. MODULATORY ROLE OF GABA AND 5HT RECEPTORS IN MIGRAINE
    F Cutrer; Fiscal Year: 1999
    ..Preliminary data indicate that valproic acid, a drug which inhibits GABA aminotransferase and which has been effective in migraine prophylaxis, blocks ..
  39. EEG-fMRI in Patients with JME
    Jerzy P Szaflarski; Fiscal Year: 2010
    ..Although seizures are typically controlled with valproic acid (VPA) or other antiepileptic drugs (AED) in about 70-80% of patients with JME, many require frequent multiple ..
  40. Targeted Therapy of Neuroendocrine Cancers Via the Notch Signaling Pathway
    Shaoqin Gong; Fiscal Year: 2013
    ..In Aim #2, whether pharmacologic activation of Notch1 using HDAC inhibitors such as valproic acid (VPA) could be a novel treatment for NE cancer patients will be determined using a murine model of recurrent/..
  41. Modeling HIV-1 Eradication Therapies in the hu-Rag2-/- gamma c-/- Mouse Model
    Shailesh K Choudhary; Fiscal Year: 2010
    ..The histone deacetylase inhibitor (HDACi) valproic acid (VPA) has recently been shown to induce resting CD4 depletion in the context of intensified antiretroviral ..
  42. Validating Electrophysiological Endophenotypes as Tranlational Biomarkers of Auti
    Michael Gandal; Fiscal Year: 2011
    ..Proposed studies will investigate AEP changes in mice treated prenatally with the teratogen valproic acid, an established rodent model of autism-like behaviors...
  43. EFFECTS OF ANTICONVULSANTS ON GLIAL ION TRANSPORT
    Steve White; Fiscal Year: 1991
    ..Thus, through an increased understanding of the mechanisms of the currently available anticonvulsant drugs and the processes underlying seizure disorders, drugs with greater selectively and fewer adverse effects can be developed...
  44. Impact of Initial Therapy and Response on Long Term Outcome in Children with CAE
    Tracy A Glauser; Fiscal Year: 2013
    ..comparative trial (NS045911 and NS045803) comparing short term outcomes for ethosuximide, lamotrigine and valproic acid as initial therapy for children with newly diagnosed CAE characterized by only absence seizures...
  45. Stepped Pharmacotherapy for Aggressive Youth with ADHD
    Joseph C Blader; Fiscal Year: 2012
    ....
  46. PHENYTOIN PATHOGENESIS OF GINGIVAL OVERGROWTH
    Thomas Hassell; Fiscal Year: 1990
    ..Four new drugs also have this side effect (cyclosporine-A, nifedipine, valproic acid, felodipine). It is estimated that 30-35 million persons will be taking such drugs within the coming decade...
  47. Growth and Develoment of the Nervous System: Molecular Mechanisms
    Cheryl F Dreyfus; Fiscal Year: 2013
    ..To achieve our goals. Project 1 will examine mechanisms by which the anticonvulsant, valproic acid affects development of neurons and glia, ranging from proliferation control to differentiation, neurotrophin ..
  48. VALPROATE RESPONSE IN AGGRESSIVE AUTISTIC ADOLESCENTS
    Jessica Hellings; Fiscal Year: 2002
    ..Study results will be prepared and submitted as manuscripts for publications and presentations. Achievement of goals of the grant will be monitored by Dr. Schroeder weekly, quarterly and annually. ..
  49. Phospho-valproic acid for pancreatic cancer prevention
    Basil Rigas; Fiscal Year: 2013
    ..We propose to study phospho-valproic acid (P-V), a novel derivative of valproic acid, as an agent for the prevention of pancreatic cancer...
  50. MIGRAINE DRUG PROPHYLAXIS
    Michael Moskowitz; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  51. GENOTYPE AND PHENOTYPE OF BRAINSTEM INJURY IN AUTISM
    Patricia Rodier; Fiscal Year: 2002
    ..In Project I. Animal Models of Autism and Mechanisms of Injury, we shall compare the effects of valproic acid, hexanoic acid and retinoic acid on the Hox gene cascade, using mice transgenic for lacZ markers of Hoxa-1 ..
  52. Microarray Analysis of Limb Bud Reaction to Teratogen E*
    William Scott; Fiscal Year: 2003
    ..Moreover, a number of these agents are well documented human teratogens such as valproic acid, retinoic acid, and ethanol...
  53. EARLY DEVELOPMENTAL GENES AND AUTISM
    Patricia Rodier; Fiscal Year: 2000
    ..Using valproic acid, we have reproduced features of the thalidomide cases in a rat model...
  54. GABA NEURONAL DYSFUNCTION IN PANIC DISORDER
    Andrew Goddard; Fiscal Year: 2000
    ..Medications that augment GABA function such as the BZDs and valproic acid, are known to be effective clinical treatments for panic disorder (PD)...
  55. CNS DELIVERY OF ALKANOATE ANTIEPILEPTICS
    Danny Shen; Fiscal Year: 1999
    The antiepileptic drug valproic acid (VPA) is a branched-chain fatty acid with unique pharmacodynamic properties...
  56. VALPROATE VERSUS LITHIUM IN BIPOLAR RAPID CYCLING
    Joseph Calabrese; Fiscal Year: 1999
    ..This study should provide novel data describing the safety and efficacy of valproate compared to lithium in a patient population with high public health significance. ..
  57. NEURAL TUBE DEFECTS INDUCED BY ANIONS VIA INCREASED PHI
    Michael Collins; Fiscal Year: 1991
    Specific organic aliphatic monocarboxylic acids (or their anions), such as the anticonvulsant valproic acid or the metabolites of environmental contaminants, 2-methoxyacetic acid and 2-ethylhexanoic acid, are teratogenic in more than a ..
  58. DIVALPROEX SODIUM/PLACEBO IN BPD
    Eric Hollander; Fiscal Year: 2000
    ....
  59. Phase II trial of valproic acid in myelodysplasia
    Peter Klein; Fiscal Year: 2006
    ..We have found that valproic acid (VPA; depakote), a widely prescribed anticonvulsant, potently inhibits histone deacetylases (HDACs) at ..
  60. NEURAL TUBE DEFECTS
    LOWELL WEITKAMP; Fiscal Year: 1990
    ..syndromes or identifiable risk factors such as maternal insulin-dependent diabetes mellitus or in utero valproic acid exposure will be excluded...
  61. Antiepileptogenic & Disease Modifying Effects of AEDs
    Asla Pitkanen; Fiscal Year: 2005
    ..abstract_text> ..
  62. MRI/MRSI Studies of Bipolar Treatment Response
    Perry Renshaw; Fiscal Year: 2009
    ..measured changes toward normal values in brain Glx were associated with lithium treatment, but not valproic acid therapy;and (3) neuroanatomic alterations identified using voxel based morphometry and shape analyses were ..
  63. Ontogeny of Drug Bioactivation and Idiosyncratic ADRs
    JAMES LEEDER; Fiscal Year: 2007
    ..Using biomarkers of acetaminophen (APAP), carbamazepine (CBZ) and valproic acid (VPA) bioactivation (and detoxification) in vivo, the goals of this research program are 1...
  64. VALPROATE, PHENYTOIN AND INFANT OUTCOME
    NONA PHILLIPS; Fiscal Year: 1992
    ..The proposed project, based on previous PHT research (58, 59, 60) and ongoing studies of VPA will provide a complete analysis of the potential effects of these two important drugs on the developing fetus and subsequent infant...
  65. Epigenetic Targeted Therapy for Chronic Lymphocytic Leu*
    John Byrd; Fiscal Year: 2005
    ..Based upon this and our previous work with histone deacetylase inhibitors including valproic acid, we seek to test the overall hypothesis that application of epigenetic therapy targeting chromatin in CLL will ..