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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
Chemical Compound Review

Depakene     2-propylpentanoic acid

Synonyms: Depakine, Ergenyl, Valproate, Vupral, Convulsofin, ...
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Disease relevance of VALPROIC ACID

  • For the control of secondarily generalized tonic-clonic seizures, carbamazepine and valproate were comparably effective (in 136 patients and 138 patients, respectively) [1].
  • Valproate was associated more frequently than carbamazepine with a weight gain of more than 5.5 kg (12 lb) (20 percent vs. 8 percent, P less than 0.001), with hair loss or change in texture (12 percent vs. 6 percent, P = 0.02), and with tremor (45 percent vs. 22 percent, P less than 0.001) [1].
  • Eighty percent of the women treated with valproate before the age of 20 years had polycystic ovaries of hyperandrogenism [2].
  • Hepatic failure from valproic acid [3].
  • Valproate is approved for use primarily in patients with absence seizures, but the drug has a broad spectrum of activity against seizures of all types [1].
  • Forty-four patients were enrolled in the phase I part, with a disease-specific cohort expansion of 15 breast cancer patients (median age, 55 years; range, 28-66 years) receiving 120 mg/kg/day valproic acid followed by FEC100 [4].

Psychiatry related information on VALPROIC ACID


High impact information on VALPROIC ACID


Chemical compound and disease context of VALPROIC ACID


Biological context of VALPROIC ACID


Anatomical context of VALPROIC ACID


Associations of VALPROIC ACID with other chemical compounds

  • We conducted a placebo-controlled, double-blind study of valproate, a drug originally developed as an antiepileptic, in 36 patients with acute manic episodes who had previously failed to respond to or to tolerate lithium carbonate [26].
  • Cortisol, valproic acid, and ACTH suppression [27].
  • As shown in this review, there is substantial evidence that valproate increases GABA synthesis and release and thereby potentiates GABAergic functions in some specific brain regions, such as substantia nigra, thought to be involved in the control of seizure generation and propagation [28].
  • The anti-viral agents ganciclovir and phosphonoformic acid (PFA) blocked valproate-induced production of infectious virus without blocking entry into the lytic cascade, and apoptosis occurred at levels that were as high as when virus production was not blocked [25].
  • In addition, we demonstrate that expression of E-cadherin, a protein involved in the control of cell migration and invasion, is highly up-regulated in the presence of valproic acid and pioglitazone [17].

Gene context of VALPROIC ACID


Analytical, diagnostic and therapeutic context of VALPROIC ACID


  1. A comparison of valproate with carbamazepine for the treatment of complex partial seizures and secondarily generalized tonic-clonic seizures in adults. The Department of Veterans Affairs Epilepsy Cooperative Study No. 264 Group. Mattson, R.H., Cramer, J.A., Collins, J.F. N. Engl. J. Med. (1992) [Pubmed]
  2. Polycystic ovaries and hyperandrogenism in women taking valproate for epilepsy. Isojärvi, J.I., Laatikainen, T.J., Pakarinen, A.J., Juntunen, K.T., Myllylä, V.V. N. Engl. J. Med. (1993) [Pubmed]
  3. Hepatic failure from valproic acid. Mathis, R.K., Hanson, R.F., Sharp, H.L. N. Engl. J. Med. (1979) [Pubmed]
  4. Clinical and biological effects of valproic acid as a histone deacetylase inhibitor on tumor and surrogate tissues: phase I/II trial of valproic acid and epirubicin/FEC. Munster, P., Marchion, D., Bicaku, E., Lacevic, M., Kim, J., Centeno, B., Daud, A., Neuger, A., Minton, S., Sullivan, D. Clin. Cancer Res. (2009) [Pubmed]
  5. Improvement of Huntington's disease with olanzapine and valproate. Grove, V.E., Quintanilla, J., DeVaney, G.T. N. Engl. J. Med. (2000) [Pubmed]
  6. Finding the intracellular signaling pathways affected by mood disorder treatments. Coyle, J.T., Duman, R.S. Neuron (2003) [Pubmed]
  7. Efficacy of valproate maintenance in patients with bipolar disorder and alcoholism: a double-blind placebo-controlled study. Salloum, I.M., Cornelius, J.R., Daley, D.C., Kirisci, L., Himmelhoch, J.M., Thase, M.E. Arch. Gen. Psychiatry (2005) [Pubmed]
  8. Reversible dementia and apparent brain atrophy during valproate therapy. Papazian, O., Cañizales, E., Alfonso, I., Archila, R., Duchowny, M., Aicardi, J. Ann. Neurol. (1995) [Pubmed]
  9. Valproic acid treatment results in increased accumulation of prion proteins. Shaked, G.M., Engelstein, R., Avraham, I., Rosenmann, H., Gabizon, R. Ann. Neurol. (2002) [Pubmed]
  10. Impaired feedback regulation of XBP1 as a genetic risk factor for bipolar disorder. Kakiuchi, C., Iwamoto, K., Ishiwata, M., Bundo, M., Kasahara, T., Kusumi, I., Tsujita, T., Okazaki, Y., Nanko, S., Kunugi, H., Sasaki, T., Kato, T. Nat. Genet. (2003) [Pubmed]
  11. Post-anoxic action myoclonus: improvement with valproic acid. Fahn, S. N. Engl. J. Med. (1978) [Pubmed]
  12. A common mechanism of action for three mood-stabilizing drugs. Williams, R.S., Cheng, L., Mudge, A.W., Harwood, A.J. Nature (2002) [Pubmed]
  13. Molecular basis of environmentally induced birth defects. Finnell, R.H., Waes, J.G., Eudy, J.D., Rosenquist, T.H. Annu. Rev. Pharmacol. Toxicol. (2002) [Pubmed]
  14. Isoniazid-induced valproic-acid toxicity, or vice versa. Dockweiler, U. Lancet (1987) [Pubmed]
  15. Drug safety in porphyria: risks of valproate and metoclopramide. Doss, M., Becker, U., Peter, H.J., Kaffarnik, H. Lancet (1981) [Pubmed]
  16. FLT3-ITD-, but not BCR/ABL-transformed cells require concurrent Akt/mTor blockage to undergo apoptosis after histone deacetylase inhibitor treatment. Cai, D., Wang, Y., Ottmann, O.G., Barth, P.J., Neubauer, A., Burchert, A. Blood (2006) [Pubmed]
  17. Peroxisome Proliferator-Activated Receptor {gamma} Regulates E-Cadherin Expression and Inhibits Growth and Invasion of Prostate Cancer. Annicotte, J.S., Iankova, I., Miard, S., Fritz, V., Sarruf, D., Abella, A., Berthe, M.L., No??l, D., Pillon, A., Iborra, F., Dubus, P., Maudelonde, T., Culine, S., Fajas, L. Mol. Cell. Biol. (2006) [Pubmed]
  18. Valproate, in combination with pemetrexed and cisplatin, provides additional efficacy to the treatment of malignant mesothelioma. Vandermeers, F., Hubert, P., Delvenne, P., Mascaux, C., Grigoriu, B., Burny, A., Scherpereel, A., Willems, L. Clin. Cancer Res. (2009) [Pubmed]
  19. Histone modifications affect timing of oligodendrocyte progenitor differentiation in the developing rat brain. Shen, S., Li, J., Casaccia-Bonnefil, P. J. Cell Biol. (2005) [Pubmed]
  20. Omega 3 fatty acids in bipolar disorder: a preliminary double-blind, placebo-controlled trial. Stoll, A.L., Severus, W.E., Freeman, M.P., Rueter, S., Zboyan, H.A., Diamond, E., Cress, K.K., Marangell, L.B. Arch. Gen. Psychiatry (1999) [Pubmed]
  21. Valproate activates bovine leukemia virus gene expression, triggers apoptosis, and induces leukemia/lymphoma regression in vivo. Achachi, A., Florins, A., Gillet, N., Debacq, C., Urbain, P., Foutsop, G.M., Vandermeers, F., Jasik, A., Reichert, M., Kerkhofs, P., Lagneaux, L., Burny, A., Kettmann, R., Willems, L. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  22. An epigenetic mouse model for molecular and behavioral neuropathologies related to schizophrenia vulnerability. Tremolizzo, L., Carboni, G., Ruzicka, W.B., Mitchell, C.P., Sugaya, I., Tueting, P., Sharma, R., Grayson, D.R., Costa, E., Guidotti, A. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  23. Valproic acid defines a novel class of HDAC inhibitors inducing differentiation of transformed cells. Göttlicher, M., Minucci, S., Zhu, P., Krämer, O.H., Schimpf, A., Giavara, S., Sleeman, J.P., Lo Coco, F., Nervi, C., Pelicci, P.G., Heinzel, T. EMBO J. (2001) [Pubmed]
  24. Reelin and glutamic acid decarboxylase67 promoter remodeling in an epigenetic methionine-induced mouse model of schizophrenia. Dong, E., Agis-Balboa, R.C., Simonini, M.V., Grayson, D.R., Costa, E., Guidotti, A. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  25. The targeting of primary effusion lymphoma cells for apoptosis by inducing lytic replication of human herpesvirus 8 while blocking virus production. Klass, C.M., Krug, L.T., Pozharskaya, V.P., Offermann, M.K. Blood (2005) [Pubmed]
  26. Valproate in the treatment of acute mania. A placebo-controlled study. Pope, H.G., McElroy, S.L., Keck, P.E., Hudson, J.I. Arch. Gen. Psychiatry (1991) [Pubmed]
  27. Cortisol, valproic acid, and ACTH suppression. Elias, A.N., Gwinup, G. Ann. Intern. Med. (1982) [Pubmed]
  28. Valproate: a reappraisal of its pharmacodynamic properties and mechanisms of action. Löscher, W. Prog. Neurobiol. (1999) [Pubmed]
  29. Valproic acid increases the SMN2 protein level: a well-known drug as a potential therapy for spinal muscular atrophy. Brichta, L., Hofmann, Y., Hahnen, E., Siebzehnrubl, F.A., Raschke, H., Blumcke, I., Eyupoglu, I.Y., Wirth, B. Hum. Mol. Genet. (2003) [Pubmed]
  30. Lithium and valproate decrease inositol mass and increase expression of the yeast INO1 and INO2 genes for inositol biosynthesis. Vaden, D.L., Ding, D., Peterson, B., Greenberg, M.L. J. Biol. Chem. (2001) [Pubmed]
  31. Expression of yeast INM1 encoding inositol monophosphatase is regulated by inositol, carbon source and growth stage and is decreased by lithium and valproate. Murray, M., Greenberg, M.L. Mol. Microbiol. (2000) [Pubmed]
  32. Lithium and valproate decrease the membrane phosphatidylinositol/phosphatidylcholine ratio. Ding, D., Greenberg, M.L. Mol. Microbiol. (2003) [Pubmed]
  33. The mood stabilizer valproic acid stimulates GABA neurogenesis from rat forebrain stem cells. Laeng, P., Pitts, R.L., Lemire, A.L., Drabik, C.E., Weiner, A., Tang, H., Thyagarajan, R., Mallon, B.S., Altar, C.A. J. Neurochem. (2004) [Pubmed]
  34. Monozygotic twins with centrotemporal EEG spikes--differences in clinical expression and effects of valproate therapy. Skarpa, D., Barisić, N., Bulat, M. N. Engl. J. Med. (1991) [Pubmed]
  35. Drug therapy: Valproic acid. Koch-Weser, J., Browne, T.R. N. Engl. J. Med. (1980) [Pubmed]
  36. Valproic-acid-induced pancytopenia and Coombs test positivity. Kaya, I.S., Dilmen, U., Toppare, M., Senses, D.A., Prentice, H.G. Lancet (1991) [Pubmed]
  37. Short-chain fatty acid derivatives induce fetal globin expression and erythropoiesis in vivo. Pace, B.S., White, G.L., Dover, G.J., Boosalis, M.S., Faller, D.V., Perrine, S.P. Blood (2002) [Pubmed]
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