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| Systematic (IUPAC) name | |
|---|---|
| 2-Propylpentanoic acid | |
| Clinical data | |
| Trade names | Depakote, Epilim, Stavzor, Vilapro |
| AHFS/Drugs.com | monograph |
| MedlinePlus | a682412 |
| Licence data | US FDA:link |
| Pregnancy cat. | D (AU) X (US) |
| Legal status | Prescription Only (S4) (AU) ℞-only (CA) POM (UK) ℞-only (US) |
| Routes | Oral, intravenous |
| Pharmacokinetic data | |
| Bioavailability | Rapid absorption |
| Protein binding | 80-90%[1] |
| Metabolism | Hepatic—glucuronide conjugation 30–50%, mitochondrial β-oxidation over 40% |
| Half-life | 9–16 hours[1] |
| Excretion | Urine (30-50%)[1] |
| Identifiers | |
| CAS number | 99-66-1 Y |
| ATC code | N03AG01 |
| PubChem | CID 3121 |
| DrugBank | DB00313 |
| ChemSpider | 3009 Y |
| UNII | 614OI1Z5WI Y |
| KEGG | D00399 Y |
| ChEBI | CHEBI:39867 Y |
| ChEMBL | CHEMBL109 Y |
| NIAID ChemDB | 057177 |
| Synonyms | 2-Propylvaleric acid |
| Chemical data | |
| Formula | C8H16O2 |
| Mol. mass | 144.211 g/mol |
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SMILES
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InChI
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| Y (what is this?) (verify) | |
Valproic acid (VPA, valproate), an acidic chemical compound, has found clinical use as an anticonvulsant and mood-stabilizing drug, primarily in the treatment of epilepsy, bipolar disorder and prevention of migraine headaches. VPA is a liquid at room temperature, but it can be reacted with a base such as sodium hydroxide to form the salt sodium valproate, which is a solid.
The acid, salt, or a mixture of the two (valproate semisodium) are marketed under a number of different brand names, including: Depakote, Epilim, Valparin, Valpro, Vilapro and Stavzor. It is on the World Health Organization's List of Essential Medicines, a list of the most important medication needed in a basic health system.[2]
Contents
- 1 Medical uses
- 2 Adverse effects
- 2.1 By frequency
- 2.2 Other possible side effects
- 2.3 Pregnancy
- 2.4 Contraindications
- 2.5 Interactions
- 2.6 Overdose and toxicity
- 3 Mechanism of action
- 4 History
- 5 Society and culture
- 5.1 Approval status
- 6 Formulations
- 7 Chemistry
- 8 See also
- 9 References
- 10 Further reading
- 11 External links
Medical uses
Its primary use in medicine is in the treatment of epilepsy, bipolar mania and migraine prophylaxis.[3] It is also used off-label for bipolar maintenance.[3] Other off-label uses include impulse control disorders, suggested by recent evidence of efficacy in controlling this adverse effect of Parkinson's Disease medical therapy.[4] Recently, it has been trialled in the treatment of HIV and cancer, owing to its histone deacetylase-inhibiting effects.[5] Valproate has a broad spectrum of anticonvulsant activity, although it is primarily used as a first-line treatment for tonic-clonic seizures, absence seizures and myoclonic seizures and as a second-line treatment for partial seizures and infantile spasms.[3][6] It has also been successfully given intravenously to treat status epilepticus.[7][8][9]
Adverse effects
The most common adverse effects of valproic acid are digestive complaints like diarrhoea, nausea, vomiting and indigestion; vision problems like seeing double or lazy eye; hormonal disturbances (increased testosterone production in females and menstrual irregularities), hair loss, memory problems, weight gain, infections, low platelet count (which can make one bleed more easily), infection, dizziness, drowsiness, tremor and headache.[3][10] Less common, yet serious side effects include liver damage, brittle bones (becomes far more common with long-term use), polycystic ovaries, movement disorders (which may be irreversible like tardive dyskinesia), psychiatric/neurologic disturbances like hallucinations, anxiety and confusion; swollen pancreas, low body temperature and potentially life-threatening blood abnormalities.[3]
By frequency
Sources:[1][3][10][11]
Very common (>10% frequency):
- Nausea
- Vomiting
- Diarrhea
- Headache
- Low platelet count (dose-related)
- Tremor (dose-related)
- Hair loss (usually temporary)
- Drowsiness
- Dizziness
- Hyperandrogenism in females
- Seeing double
- Indigestion
- Lazy eye
- Infection
- Tinnitus
- Elevated aminotransferase concentrations (dose-related; indicative of liver injury)
Common (1-10% frequency):
- Paraesthesia
- Abdominal pain
- Tremor
- Increased appetite
- Weight gain
- Ataxia
- Polycystic ovaries
- Memory impairment
- Menstrual irregularities
- Rash
- Back pain
- Mood changes
- Anxiety
- Confusion
- Abnormal gait
- Hallucinations
- Catatonia
- Dysarthria
- Tardive dyskinesia
- Vertigo
- High blood levels of ammonia without symptoms
Uncommon (0.1-1% frequency):
- Peripheral oedema
- SIADH
Rare (<0.1% frequency):
- Liver failure
- Pancreatitis (these two usually occur in first 6 months and can be fatal)
- Leucopenia (low white blood cell count)
- Neutropenia (low neutrophil count)
- Pure red cell aplasia
- Agranulocytosis
- Extrapyramidal syndrome (including parkinsonism, may be reversible)
- Brain problems due to high ammonia levels
- Hypothermia
- Hypersensitivity reactions including multi-organ hypersensitivity syndrome
- Eosinophilic pleural effusion
- Bone fractures (reduced BMD with long-term use)
Other possible side effects
There is evidence that valproic acid may cause premature growth plate ossification in children and adolescents, resulting in short stature.[12][13][14][15]
Pregnancy
Valproate causes birth defects; exposure during pregnancy is associated with about three times as many major anomalies as usual, mainly spina bifida and, more rarely, with several other defects, possibly including a "valproate syndrome".[16] Characteristics of this valproate syndrome include facial features that tend to evolve with age, including trigonocephaly, tall forehead with bifrontal narrowing, epicanthic folds, medial deficiency of eyebrows, flat nasal bridge, broad nasal root, anteverted nares, shallow philtrum, long upper lip and thin vermillion borders, thick lower lip and small downturned mouth.[17]
Women who intend to become pregnant should switch to a different drug if possible.[18] Women who become pregnant while taking valproate should be warned that it causes birth defects and cognitive impairment in the newborn, especially at high doses (although vaproate is sometimes the only drug that can control seizures, and seizures in pregnancy could have even worse consequences.) They should take high-dose folic acid and be offered antenatal screening (alpha-fetoprotein and second-trimester ultrasound scans), although screening and scans do not find all birth defects.[19]
Valproate can cause neural tube defects. Folic acid supplements may reduce the risk of birth defects, however. A recent study showed children of mothers taking valproate during pregnancy are at risk for significantly lower IQs.[20][21][22] Maternal valproate use during pregnancy has been associated with a significantly higher risk of autism in the offspring.[23] Exposure of the human embryo to valproic acid is associated with risk of autism, and it is possible to duplicate features characteristic of autism by exposing rat embryos to valproic acid at the time of neural tube closure.[24] Valproate exposure on embryonic day 11.5 led to significant local recurrent connectivity in the juvenile rat neocortex, consistent with the underconnectivity theory of autism.[25] A 2009 study found that the 3 year old children of pregnant women taking valproate had an IQ nine points lower than that of a well-matched control group. However, further research in older children and adults is needed.[26][27][28]
Contraindications
Contraindications include:[11]
- Pregnancy
- Pre-existing acute or chronic hepatic dysfunction or family history of severe hepatitis, particularly medicine related.
- Known hypersensitivity to valproate or any of the excipients used in the preparation
- Urea cycle disorders
- Hepatic porphyria
- Hepatotoxicity[11]
- Mitochondrial disease[11]
- Pancreatitis[11]
Interactions
Valproate inhibits CYP2C9, glucuronyl transferase, and epoxide hydrolase and is highly protein bound and hence may interact with drugs that are substrates for any of these enzymes or are highly protein bound themselves.[11] It may also potentiate the CNS depressant effects of alcohol.[11] It should not be given in conjunction with other antiepileptics due to the potential for reduced clearance of other antiepileptics (including carbamazepine, lamotrigine, phenytoin and phenobarbitone) and itself.[11] It may also interact with:[11]
- Anticoagulants, due to its ability to prolong the bleeding time.
- Psychotropic agents; potential pharmacokinetic interactions.
- Benzodiazepines; may potentiate CNS depression and there are possible pharmacokinetic interactions.
- Ethosuximide; potential for ethosuximide toxicity.
- Primidone; may reduce pyrimidone's clearance leading to toxicity.
- Zidovudine; may raise its (zidovudine's) serum concentration and lead to toxicity.
- Aspirin; may displace valproate from plasma proteins, leading to increased plasma concentrations. Also interferes with valproate's metabolism.
- Felbalmate; may increase plasma concentrations of valproate.
- Mefloquine; potential for increased valproate metabolism combined with the direct epileptogenic effects of mefloquine.
- Cimetidine; inhibits valproate's metabolism in the liver, hence leading to reduced plasma concentrations of valproate.
- Erythromycin; inhibits valproate's metabolism in the liver, hence leading to increased plasma concentrations of valproate.
- Carbapenem antibiotics; reduces valproate levels, potentially leading to seizures.
Overdose and toxicity
Excessive amounts of valproic acid can result in tremor, stupor, respiratory depression, coma, metabolic acidosis, and death. Overdosage in children is usually of an accidental nature, whereas with adults it is more likely to be an intentional act. In general, serum or plasma valproic acid concentrations are in a range of 20–100 mg/l during controlled therapy, but may reach 150–1500 mg/l following acute poisoning. Monitoring of the serum level is often accomplished using commercial immunoassay techniques, although some laboratories employ gas or liquid chromatography.[29] In contrast to other antiepileptic drugs, at present there is little evidence favorable evidence for salivary therapeutic drug monitoring. Salivary levels of valproic acid correlate poorly with serum levels, at least in part due to valproate's weak acid property (pKa of 4.9).[30]
In severe intoxication, hemoperfusion or hemofiltration can be an effective means of hastening elimination of the drug from the body.[31][32] Supplemental L-carnitine is indicated in patients having an acute overdose[33][34] and also prophylactically[33] in high risk patients. Acetyl-L-carnitine lowers hyperammonemia less markedly[35] than L-carnitine.
Mechanism of action
Although the mechanism of action of valproate is not fully understood,[11] it has recently been shown to protect against a seizure-induced reduction in phosphatidylinositol (3,4,5)-trisphosphate (PIP3) as a potential therapeutic mechanism.[36] In addition, its anticonvulsant effect has been attributed to the blockade of voltage-dependent sodium channels and increased brain levels of gamma-aminobutyric acid (GABA).[11] The GABAergic effect is also believed to contribute towards the anti-manic properties of valproate.[11] In animals, sodium valproate raises cerebral and cerebellar levels of the inhibitory synaptic transmitter, GABA, possibly by inhibiting GABA degradative enzymes, such as GABA transaminase, succinate-semialdehyde dehydrogenase and by inhibiting the re-uptake of GABA by neuronal cells.[11] It also possesses histone deacetylase-inhibiting effects. The inhibition of histone deacetylase, by promoting more transcriptionally active chromatin structures, likely presents the epigenetic mechanism for regulation of many of the neuroprotective effects attributed to valproic acid. Intermediate molecules mediating these effects include VEGF, BDNF, and GDNF. [37][38]
History
Valproic acid was first synthesized in 1882 by B.S. Burton as an analogue of valeric acid, found naturally in valerian.[39] Valproic acid is a carboxylic acid, a clear liquid at room temperature. For many decades, its only use was in laboratories as a "metabolically inert" solvent for organic compounds. In 1962, the French researcher Pierre Eymard serendipitously discovered the anticonvulsant properties of valproic acid while using it as a vehicle for a number of other compounds that were being screened for antiseizure activity. He found it prevented pentylenetetrazol-induced convulsions in laboratory rats.[40] It was approved as an antiepileptic drug in 1967 in France and has become the most widely prescribed antiepileptic drug worldwide.[41] Valproic acid has also been used for migraine prophylaxis and bipolar disorder.[42]
Society and culture
Approval status
| Indications | FDA-labelled indication?[1] |
TGA-labelled indication?[3] |
MHRA-labelled indication?[10] |
Literature support |
|---|---|---|---|---|
| Epilepsy | Yes | Yes | Yes | Limited.[43] |
| Bipolar mania | Yes | Yes | Yes | Limited.[44] |
| Bipolar depression | No | No | No | Moderate.[45] |
| Bipolar maintenance | No | No | No | Limited.[46] |
| Migraine prophylaxis | Yes | No | No | Limited. |
| Acute migraine management | No | No | No | Only negative results.[47] |
| Schizophrenia | No | No | No | Weak and mostly negative evidence.[48] |
| Agitation in dementia | No | No | No | Weak and mostly negative evidence.[49] |
| Fragile X Syndrome | Yes (orphan) | No | No | Limited.[50] |
| Familial Adenomatous Polyposis | Yes (orphan) | No | No | Limited. |
| Chronic pain & fibromyalgia | No | No | No | Limited.[51] |
| Alcohol hallucinosis | No | No | No | One randomised double-blind placebo-controlled trial.[52] |
| Intractable hiccups | No | No | No | Limited, five case reports support its efficacy, however.[53] |
| Non-epileptic myoclonus | No | No | No | Limited, three case reports support its efficacy, however.[54] |
| Cluster headaches | No | No | No | Limited, two case reports support its efficacy.[55] |
| West syndrome | No | No | No | A prospective clinical trial supported its efficacy in treating infantile spasms.[56] |
| HIV infection eradication | No | No | No | Double-blind placebo-controlled trials have been negative.[57][58][59] |
| Myelodysplastic syndrome | No | No | No | Several clinical trials have confirmed its efficacy as a monotherapy,[60] as an adjunct to tretinoin[60] and as an adjunct to hydralazine.[61] |
| Acute myeloid leukaemia | No | No | No | Two clnical trials have confirmed its efficacy in this indication as both a monotherapy and as an adjunct to tretinoin.[62][63][64] |
| Cervical cancer | No | No | No | One clinical trial supports its use here.[65] |
| Malignant melanoma | No | No | No | One phase II study has seemed to discount its efficacy.[66] |
| Breast cancer | No | No | No | A phase II study has supported its efficacy.[67] |
| Impulse Control Disorder | No | No | No | Limited.[68][4] |
Formulations
Branded products include:
- Absenor (Orion Corporation Finland)
- Convulex (Pfizer in the UK and Byk Madaus in South Africa)
- Depakene (Abbott Laboratories in U.S. & Canada)
- Depakine (Sanofi Aventis France)
- Depakine (Sanofi Synthelabo Romania)
- Depalept (Sanofi Aventis Israel)
- Deprakine (Sanofi Aventis Finland)
- Encorate (Sun Pharmaceuticals India)
- Epival (Abbott Laboratories U.S. & Canada)
- Epilim (Sanofi Synthelabo Australia)
- Stavzor (Noven Pharmaceuticals Inc.)
- Valcote (Abbott Laboratories Argentina)
- Valpakine (Sanofi Aventis Brazil)
Chemistry
Valproic acid, 2-propylvaleric acid, is synthesized by the alkylation of ethyl cyanoacetate with two equivalents of propyl bromide, to give dipropylcyanoacetic ester. Hydrolysis and decarboxylation of the carboethoxy group gives 2-propylpentanenitrile, which is hydrolyzed into valproic acid.[69][70][71][72]
See also
- Sodium valproate
- Valproate semisodium
References
- ^ a b c d e "Depakene, Stavzor (valproic acid) dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD. Retrieved 13 February 2014.
- ^ "WHO Model List of EssentialMedicines". World Health Organization. October 2013. Retrieved 22 April 2014.
- ^ a b c d e f g Rossi, S, ed. (2013). Australian Medicines Handbook (2013 ed.). Adelaide: The Australian Medicines Handbook Unit Trust. ISBN 978-0-9805790-9-3. edit
- ^ a b Hicks, CW; Pandya, Itin, Fernandez (Jun 2011). "Valproate for the treatment of medication-induced impulse-control disorders in three patients with Parkinson's disease.". Parkinsonism & Related Disorders 17 (5): 379–81. PMID 21459656. Retrieved 20 April 2014. Cite uses deprecated parameters (help)
- ^ Činčárová, L; Zdráhal, Z; Fajkus, J (December 2013). "New perspectives of valproic acid in clinical practice". Expert Opinion on Investigational Drugs 22 (12): 1535–1547. doi:10.1517/13543784.2013.853037. PMID 24160174. Cite uses deprecated parameters (help)
- ^ Löscher, W (2002). "Basic pharmacology of valproate: a review after 35 years of clinical use for the treatment of epilepsy.". CNS drugs 16 (10): 669–694. doi:10.2165/00023210-200216100-00003. PMID 12269861.
- ^ Olsen, KB; Taubøll, E; Gjerstad, L (2007). "Valproate is an effective, well-tolerated drug for treatment of status epilepticus/serial attacks in adults.". Acta Neurologica Scandinavica 187: 51–4. doi:10.1111/j.1600-0404.2007.00847.x. PMID 17419829. Cite uses deprecated parameters (help)
- ^ Kwan, SY (June 2010). "The role of intravenous valproate in convulsive status epilepticus in the future." (PDF). Acta Neurologica Taiwanica 19 (2): 78–81. PMID 20830628.
- ^ Tiamkao, Somsak; Sawanyawisuth, Kittisak; Chancharoen, Alongkorn (2013). "The efficacy of intravenous sodium valproate and phenytoin as the first-line treatment in status epilepticus: a comparison study" (PDF). BMC Neurology 13 (1): 98. doi:10.1186/1471-2377-13-98. PMC 3727978. PMID 23889906. Cite uses deprecated parameters (help)
- ^ a b c Joint Formulary Committee (2013). British National Formulary (BNF) (65 ed.). London, UK: Pharmaceutical Press. ISBN 978-0-85711-084-8. edit
- ^ a b c d e f g h i j k l m "Valpro sodium valproate" (PDF). TGA eBusiness Services. Alphapharm Pty Limited. 16 December 2013. Retrieved 14 February 2014.
- ^ Effects of valproic acid on longitudinal bone... [J Child Neurol. 2004] - PubMed - NCBI
- ^ Inhibition of cartilage growth by the anticonvulsant drugs diphenylhydantoin and sodium valproate
- ^ Long-Term Valproate and Lamotrigine Treatment May Be a Marker for Reduced Growth and Bone Mass in Children with Epilepsy - Guo - 2002 - Epilepsia - Wiley Online Library
- ^ Long-term valproate and lamotrigine treatment may ... [Epilepsia. 2001] - PubMed - NCBI
- ^ Ornoy, A. (2009). "Valproic acid in pregnancy: How much are we endangering the embryo and fetus?". Reproductive Toxicology 28 (1): 1–10. doi:10.1016/j.reprotox.2009.02.014. PMID 19490988. edit
- ^ Kulkarni, M. L.; Zaheeruddin, M.; Shenoy, N.; Vani, H. N. (2006). "Fetal valproate syndrome". Indian journal of pediatrics 73 (10): 937–939. PMID 17090909. edit
- ^ Valproate Not To Be Used for Migraine During Pregnancy, FDA Warns
- ^ British National Formulary (March 2003) 45
- ^ Umur, A. S.; Selcuki, M.; Bursali, A.; Umur, N.; Kara, B.; Vatansever, H. S.; Duransoy, Y. K. (2012). "Simultaneous folate intake may prevent advers effect of valproic acid on neurulating nervous system". Child's Nervous System 28 (5): 729–737. doi:10.1007/s00381-011-1673-9. PMID 22246336. edit
- ^ Cassels, Caroline (December 8, 2006). "NEAD: In Utero Exposure To Valproate Linked to Poor Cognitive Outcomes in Kids". Medscape. Retrieved 2007-05-23.
- ^ Meador, K. J.; Baker, G. A.; Finnell, R. H.; Kalayjian, L. A.; Liporace, J. D.; Loring, D. W.; Mawer, G.; Pennell, P. B.; Smith, J. C.; Wolff, M. C.; Nead Study, G. (2006). "In utero antiepileptic drug exposure: Fetal death and malformations". Neurology 67 (3): 407–412. doi:10.1212/01.wnl.0000227919.81208.b2. PMC 1986655. PMID 16894099. edit
- ^ Christensen, J.; Grønborg, T. K.; Sørensen, M. J.; Schendel, D.; Parner, E. T.; Pedersen, L. H.; Vestergaard, M. (2013). "Prenatal Valproate Exposure and Risk of Autism Spectrum Disorders and Childhood Autism". JAMA 309 (16): 1696–1703. doi:10.1001/jama.2013.2270. PMID 23613074. edit
- ^ Arndt, T. L.; Stodgell, C. J.; Rodier, P. M. (2005). "The teratology of autism". International Journal of Developmental Neuroscience 23 (2–3): 189–199. doi:10.1016/j.ijdevneu.2004.11.001. PMID 15749245. edit
- ^ Rinaldi, T.; Silberberg, G.; Markram, H. (2007). "Hyperconnectivity of Local Neocortical Microcircuitry Induced by Prenatal Exposure to Valproic Acid". Cerebral Cortex 18 (4): 763–770. doi:10.1093/cercor/bhm117. PMID 17638926. edit
- ^ I.Q. Harmed by Epilepsy Drug in Utero By RONI CARYN RABIN, New York Times, April 15, 2009
- ^ Meador, K. J.; Baker, G. A.; Browning, N.; Clayton-Smith, J.; Combs-Cantrell, D. T.; Cohen, M.; Kalayjian, L. A.; Kanner, A.; Liporace, J. D.; Pennell, P. B.; Privitera, M.; Loring, D. W.; Nead Study, G. (2009). "Cognitive Function at 3 Years of Age after Fetal Exposure to Antiepileptic Drugs". New England Journal of Medicine 360 (16): 1597–1605. doi:10.1056/NEJMoa0803531. PMC 2737185. PMID 19369666. edit
- ^ Valproate Products: Drug Safety Communication - Risk of Impaired Cognitive Development in Children Exposed In Utero (During Pregnancy). FDA. June 2011
- ^ Sztajnkrycer, M. D. (2002). "Valproic acid toxicity: Overview and management". Journal of toxicology. Clinical toxicology 40 (6): 789–801. doi:10.1081/CLT-120014645. PMID 12475192. edit
- ^ Patsalos, PN; Berry (Feb 2013). "Therapeutic drug monitoring of antiepileptic drugs by use of saliva". Therapeutic Drug Monitoring 35 (1): 4–29. PMID 23288091. Cite uses deprecated parameters (help);
|accessdate=requires|url=(help) - ^ Thanacoody, R. H. K. (2009). "Extracorporeal elimination in acute valproic acid poisoning". Clinical Toxicology 47 (7): 609–616. doi:10.1080/15563650903167772. PMID 19656009. edit
- ^ R. Baselt, Disposition of Toxic Drugs and Chemicals in Man, 8th edition, Biomedical Publications, Foster City, CA, 2008, pp. 1622-1626.
- ^ a b Lheureux, P. E.; Penaloza, A.; Zahir, S.; Gris, M. (2005). "Science review: Carnitine in the treatment of valproic acid-induced toxicity - what is the evidence?". Critical Care 9 (5): 431–440. doi:10.1186/cc3742. PMC 1297603. PMID 16277730. edit
- ^ Mock, C. M.; Schwetschenau, K. H. (2011). "Levocarnitine for valproic-acid-induced hyperammonemic encephalopathy". American Journal of Health-System Pharmacy 69 (1): 35–39. doi:10.2146/ajhp110049. PMID 22180549. edit
- ^ Matsuoka, M.; Igisu, H. (1993). "Comparison of the effects of L-carnitine, D-carnitine and acetyl-L-carnitine on the neurotoxicity of ammonia". Biochemical pharmacology 46 (1): 159–164. doi:10.1016/0006-2952(93)90360-9. PMID 8347126. edit
- ^ Chang, P; Walker, M. C.; Williams, R. S. (2014). "Seizure-induced reduction in PIP3 levels contributes to seizure-activity and is rescued by valproic acid". Neurobiology of Disease 62: 296–306. doi:10.1016/j.nbd.2013.10.017. PMC 3898270. PMID 24148856. edit
- ^ Kostrouchová, M; Kostrouch, Z; Kostrouchová, M (2007). "Valproic acid, a molecular lead to multiple regulatory pathways." (PDF). Folia biologica 53 (2): 37–49. PMID 17448293. Cite uses deprecated parameters (help)
- ^ Chiu, CT; Wang, Hunsberger, Chuang (Jan 8, 2013). "Therapeutic potential of mood stabilizers lithium and calproic acid: beyond bipolar disorder". Pharmacological Reviews 65 (1): 105–142. PMID 23300133. Retrieved 20 April 2014. Cite uses deprecated parameters (help)
- ^ Burton B.S. (1882). "On the propyl derivatives and decomposition products of ethylacetoacetate". Am Chem J. 3: 385–395.
- ^ Meunier, H.; Carraz, G.; Neunier, Y.; Eymard, P.; Aimard, M. (1963). "Pharmacodynamic properties of N-dipropylacetic acid". Therapie 18: 435–438. PMID 13935231. edit
- ^ Perucca, E. (2002). "Pharmacological and therapeutic properties of valproate: A summary after 35 years of clinical experience". CNS drugs 16 (10): 695–714. doi:10.2165/00023210-200216100-00004. PMID 12269862. edit
- ^ Henry, T. R. (2003). "The history of valproate in clinical neuroscience". Psychopharmacology bulletin. 37 Suppl 2: 5–16. PMID 14624229. edit
- ^ Rimmer, EM; Richens, A (May–June 1985). "An update on sodium valproate.". Pharmacotherapy 5 (3): 171–84. doi:10.1002/j.1875-9114.1985.tb03413.x. PMID 3927267. Cite uses deprecated parameters (help)
- ^ Vasudev, K; Mead, A; Macritchie, K; Young, AH (2012). "Valproate in acute mania: is our practice evidence based?". International Journal of Health Care Quality Assurance 25 (1): 41–52. doi:10.1108/09526861211192395. PMID 22455007. Cite uses deprecated parameters (help)
- ^ Bond, DJ; Lam, RW; Yatham, LN (August 2010). "Divalproex sodium versus placebo in the treatment of acute bipolar depression: a systematic review and meta-analysis.". Journal of Affective Disorders 124 (3): 228–334. doi:10.1016/j.jad.2009.11.008. PMID 20044142. Cite uses deprecated parameters (help)
- ^ Haddad, PM; Das, A; Ashfaq, M; Wieck, A (May 2009). "A review of valproate in psychiatric practice.". Expert Opinion on Drug Metabolism & toxicology 5 (5): 539–51. doi:10.1517/17425250902911455. PMID 19409030. Cite uses deprecated parameters (help)
- ^ Frazee, LA; Foraker, KC (March 2008). "Use of intravenous valproic acid for acute migraine.". The Annals of pharmacotherapy 42 (3): 403–7. doi:10.1345/aph.1K531. PMID 18303140. Cite uses deprecated parameters (help)
- ^ Schwarz, C; Volz, A; Li, C; Leucht, S (16 July 2008). "Valproate for schizophrenia." (PDF). The Cochrane database of systematic reviews (3): CD004028. doi:10.1002/14651858.CD004028.pub3. PMID 18646098. Cite uses deprecated parameters (help)
- ^ Lonergan, E; Luxenberg, J (8 July 2009). "Valproate preparations for agitation in dementia." (PDF). The Cochrane Database of Systematic Reviews (3): CD003945. doi:10.1002/14651858.CD003945.pub3. PMID 19588348. Cite uses deprecated parameters (help)
- ^ Chiu, CT; Wang, Z; Hunsberger, JG; Chuang, DM (January 2013). "Therapeutic potential of mood stabilizers lithium and valproic acid: beyond bipolar disorder." (PDF). Pharmacological reviews 65 (1): 105–142. doi:10.1124/pr.111.005512. PMC 3565922. PMID 23300133. Cite uses deprecated parameters (help)
- ^ Gill, D; Derry, S; Wiffen, PJ; Moore, RA (5 October 2011). "Valproic acid and sodium valproate for neuropathic pain and fibromyalgia in adults." (PDF). The Cochrane Database of Systematic Reviews (10): CD009183. doi:10.1002/14651858.CD009183.pub2. PMID 21975791. Cite uses deprecated parameters (help)
- ^ Aliyev, ZN; Aliyev, NA (July–August 2008). "Valproate treatment of acute alcohol hallucinosis: a double-blind, placebo-controlled study." (PDF). Alcohol and alcoholism (Oxford, Oxfordshire) 43 (4): 456–459. doi:10.1093/alcalc/agn043. PMID 18495806. Cite uses deprecated parameters (help)
- ^ Jacobson, P. L.; Messenheimer, J. A.; Farmer, T. W. (1 November 1981). "Treatment of intractable hiccups with valproic acid". Neurology 31 (11): 1458–1458. doi:10.1212/WNL.31.11.1458. PMID 6796902. Cite uses deprecated parameters (help)
- ^ Sotaniemi, K (July 1982). "Valproic acid in the treatment of nonepileptic myoclonus.". Archives of Neurology 39 (7): 448–9. doi:10.1001/archneur.1982.00510190066025. PMID 6808975.
- ^ Wheeler, SD (July–August 1998). "Significance of migrainous features in cluster headache: divalproex responsiveness.". Headache 38 (7): 547–51. doi:10.1046/j.1526-4610.1998.3807547.x. PMID 15613172.
- ^ Siemes, H; Spohr, HL; Michael, T; Nau, H (September–October 1988). "Therapy of infantile spasms with valproate: results of a prospective study.". Epilepsia 29 (5): 553–60. PMID 2842127. Cite uses deprecated parameters (help)
- ^ Smith, SM (2005). "Valproic acid and HIV-1 latency: beyond the sound bite" (PDF). Retrovirology 2 (1): 56. doi:10.1186/1742-4690-2-56. PMID 16168066.
- ^ Routy, JP; Tremblay, CL; Angel, JB; Trottier, B; Rouleau, D; Baril, JG; Harris, M; Trottier, S; Singer, J; Chomont, N; Sékaly, RP; Boulassel, MR (May 2012). "Valproic acid in association with highly active antiretroviral therapy for reducing systemic HIV-1 reservoirs: results from a multicentre randomized clinical study.". HIV Medicine 13 (5): 291–6. doi:10.1111/j.1468-1293.2011.00975.x. PMID 22276680. Cite uses deprecated parameters (help)
- ^ Archin, NM; Cheema, M; Parker, D; Wiegand, A; Bosch, RJ; Coffin, JM; Eron, J; Cohen, M; Margolis, DM (23 February 2010). "Antiretroviral intensification and valproic acid lack sustained effect on residual HIV-1 viremia or resting CD4+ cell infection." (PDF). PloS one 5 (2): e9390. doi:10.1371/journal.pone.0009390. PMC 2826423. PMID 20186346. Cite uses deprecated parameters (help)
- ^ a b Hardy, JR; Rees, EA; Gwilliam, B; Ling, J; Broadley, K; A'Hern, R (March 2001). "A phase II study to establish the efficacy and toxicity of sodium valproate in patients with cancer-related neuropathic pain." (PDF). Journal of Pain and Symptom Management 21 (3): 204–9. doi:10.1016/S0885-3924(00)00266-9. PMID 11239739. Cite uses deprecated parameters (help)
- ^ Candelaria, M; Herrera, A; Labardini, J; González-Fierro, A; Trejo-Becerril, C; Taja-Chayeb, L; Pérez-Cárdenas, E; Cruz-Hernández, E; Arias-Bofill, D; Vidal, S; Cervera, E; Dueñas-Gonzalez, A (5 October 2010). "Hydralazine and magnesium valproate as epigenetic treatment for myelodysplastic syndrome. Preliminary results of a phase-II trial". Annals of Hematology 90 (4): 379–387. doi:10.1007/s00277-010-1090-2. PMID 20922525. Cite uses deprecated parameters (help)
- ^ Bug, G; Ritter, M; Wassmann, B; Schoch, C; Heinzel, T; Schwarz, K; Romanski, A; Kramer, OH; Kampfmann, M; Hoelzer, D; Neubauer, A; Ruthardt, M; Ottmann, OG (15 December 2005). "Clinical trial of valproic acid and all-trans retinoic acid in patients with poor-risk acute myeloid leukemia." (PDF). Cancer 104 (12): 2717–2725. doi:10.1002/cncr.21589. PMID 16294345. Cite uses deprecated parameters (help)
- ^ Kuendgen, A; Schmid, M; Schlenk, R; Knipp, S; Hildebrandt, B; Steidl, C; Germing, U; Haas, R; Dohner, H; Gattermann, N (1 January 2006). "The histone deacetylase (HDAC) inhibitor valproic acid as monotherapy or in combination with all-trans retinoic acid in patients with acute myeloid leukemia." (PDF). Cancer 106 (1): 112–119. doi:10.1002/cncr.21552. PMID 16323176. Cite uses deprecated parameters (help)
- ^ Fredly, H; Gjertsen, BT; Bruserud, O (30 July 2013). "Histone deacetylase inhibition in the treatment of acute myeloid leukemia: the effects of valproic acid on leukemic cells, and the clinical and experimental evidence for combining valproic acid with other antileukemic agents." (PDF). Clinical Epigenetics 5 (1): 12. doi:10.1186/1868-7083-5-12. PMC 3733883. PMID 23898968. Cite uses deprecated parameters (help)
- ^ Coronel, J; Cetina, L; Pacheco, I; Trejo-Becerril, C; González-Fierro, A; de la Cruz-Hernandez, E; Perez-Cardenas, E; Taja-Chayeb, L; Arias-Bofill, D; Candelaria, M; Vidal, S; Dueñas-González, A (December 2011). "A double-blind, placebo-controlled, randomized phase III trial of chemotherapy plus epigenetic therapy with hydralazine valproate for advanced cervical cancer. Preliminary results.". Medical Oncology. 28 Suppl 1: S540–6. doi:10.1007/s12032-010-9700-3. PMID 20931299. Cite uses deprecated parameters (help)
- ^ Rocca, A; Minucci, S; Tosti, G; Croci, D; Contegno, F; Ballarini, M; Nolè, F; Munzone, E; Salmaggi, A; Goldhirsch, A; Pelicci, PG; Testori, A (13 January 2009). "A phase I-II study of the histone deacetylase inhibitor valproic acid plus chemoimmunotherapy in patients with advanced melanoma." (PDF). British Journal of Cancer 100 (1): 28–36. doi:10.1038/sj.bjc.6604817. PMC 2634690. PMID 19127265. Cite uses deprecated parameters (help)
- ^ Munster, P; Marchion, D; Bicaku, E; Lacevic, M; Kim, J; Centeno, B; Daud, A; Neuger, A; Minton, S; Sullivan, D (1 April 2009). "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." (PDF). Clinical Cancer Research 15 (7): 2488–96. doi:10.1158/1078-0432.CCR-08-1930. PMID 19318486. Cite uses deprecated parameters (help)
- ^ Sriram, A; Ward, Hassan, Iyer, Foot, Rodriguez, McFarland, Okun (Feb 2013). "Valproate as a treatment for dopamine dysregulation syndrome (DDS) in Parkinson's disease". Journal of Neurology 260 (2): 521-7. PMID 23007193. Retrieved 20 April 2014. Cite uses deprecated parameters (help)
- ^ M. Chignac, C. Grain, U.S. Patent 4,155,929 (1979)
- ^ H.E.J.-M. Meunier, GB 980279 (1963)
- ^ H.E.J.-M. Meunier, U.S. Patent 3,325,361(1967)
- ^ M. Chignac, C. Grain, Ch. Pigerol, GB 1522450 (1977)
Further reading
- Chateauvieux, S. B.; Morceau, F.; Dicato, M.; Diederich, M. (2010). "Molecular and Therapeutic Potential and Toxicity of Valproic Acid" (PDF). Journal of Biomedicine and Biotechnology 2010: 1. doi:10.1155/2010/479364. PMC 2926634. PMID 20798865. edit
- Monti, B.; Polazzi, E.; Contestabile, A. (2009). "Biochemical, molecular and epigenetic mechanisms of valproic acid neuroprotection" (PDF). Current molecular pharmacology 2 (1): 95–109. PMID 20021450. edit
External links
- PsychEducation: Valproate/divalproex (divalproex)
- The Comparative Toxicogenomics Database:Valproic Acid
- Chemical Land21: Valproic Acid
- RXList.com: Depakene (Valproic Acid) (U.S.)
- South African Electronic Package Inserts: Convulex
- Med Broadcast.com: Valproic Acid (Canadian)
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UpToDate Contents
全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.
- 1. バルプロ酸中毒 valproic acid poisoning
- 2. 抗てんかん剤：作用機序、薬理学、および有害事象 antiepileptic drugs mechanism of action pharmacology and adverse effects
- 3. 成人における双極性障害：急性躁病および軽躁に対する薬物療法 bipolar disorder in adults pharmacotherapy for acute mania and hypomania
- 4. てんかんおよび妊娠に関連するリスク risks associated with epilepsy and pregnancy
- 5. 思春期における多嚢胞性卵巣症候群の診断的評価 diagnostic evaluation of polycystic ovary syndrome in adolescents
English Journal
- Valproic acid-induced hyperammonemic encephalopathy - a potentially fatal adverse drug reaction.
- Sousa C.SourcePharmacy, Hospital de Faro, EPE, Rua Leao Penedo, Faro, 8000-386 Portugal.
- SpringerPlus.Springerplus.2013 Dec;2(1):13. Epub 2013 Jan 15.
- BACKGROUND: A patient with an early diagnosed epilepsy Valproic acid is one of the most widely used antiepileptic drugs. Hyperammonemic encephalopathy is a rare, but potentially fatal, adverse drug reaction to valproic acid.CASE DESCRIPTION: A patient with an early diagnosed epilepsy, treated with v
- PMID 23451336
- Effects of antiepileptic drugs on antioxidant and oxidant molecular pathways: focus on trace elements.
- Nazıroğlu M, Yürekli VA.SourceNeurocience Research Center, Suleyman Demirel University, Tıp Fakültesi Binasi, 32260, Isparta, Turkey, mustafanaziroglu@sdu.edu.tr.
- Cellular and molecular neurobiology.Cell Mol Neurobiol.2013 Jul;33(5):589-99. doi: 10.1007/s10571-013-9936-5. Epub 2013 Apr 14.
- Current reports on trace elements, oxidative stress, and the effect of antiepileptic drugs are poor and controversial. We aimed to review effects of most common used antiepileptics on antioxidant, trace element, calcium ion (Ca(2+)) influx, and oxidant systems in human and experimental animal models
- PMID 23584684
- Valproic Acid use during radiation therapy for glioblastoma associated with improved survival.
- Barker CA, Bishop AJ, Chang M, Beal K, Chan TA.SourceDepartment of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York. Electronic address: barkerc@mskcc.org.
- International journal of radiation oncology, biology, physics.Int J Radiat Oncol Biol Phys.2013 Jul 1;86(3):504-9. doi: 10.1016/j.ijrobp.2013.02.012. Epub 2013 Mar 20.
- PURPOSE: Valproic acid (VA) is an antiepileptic drug (AED) and histone deacetylase (HDAC) inhibitor taken by patients with glioblastoma (GB) to manage seizures, and it can modulate the biologic effects of radiation therapy (RT). We investigated whether VA use during RT for GB was associated with ove
- PMID 23523186
Japanese Journal
- Depakote adjunctive therapy in the treatment of partial seizures
- WILLMORE JL.
- Epilepsia 36(suppl 3), S66, 1995
- NAID 10009184814
- Positive response to oral divalproex sodium (Depakote) in patients with spasticity and pain
- ZACHARIAH GH.
- Am J Med Sci 308, 38-40, 173-187, 1994
- NAID 30009097115
Related Links
- Learn about prescription Depakote® (divalproex sodium) as an add‐on treatment for epilepsy, or bipolar mania. Learn about the benefits and risks. ... BEFORE starting Depakote, tell your healthcare provider if you: Have liver disease ...
- Depakote is used to treat various types of seizure disorders. Learn about side effects, interactions and indications. ... Depakote side effects Get emergency medical help if you have any of these signs of an allergic reaction: to ...
Related Pictures
★リンクテーブル★
| リンク元 | 「バルプロ酸」 |
| 関連記事 | 「depakote」 |
「バルプロ酸」
- 英
- valproic acid
- 同
- ジプロピル酢酸 dipropylacetic acid
- 化
- バルプロ酸ナトリウム sodium valproate, valproate sodium
- 商
- エピレナート、サノテン、セレニカR、プロモーション、セレブ、デパケン、ハイセレニン、バルデケンR、バルプラム、バレリン、Depakene, Depakote, Epival
- 関
- てんかん、バルプロ酸ナトリウム中毒
特徴
作用機序
- GABAトランスアミナーゼを阻害(SPC.187)
薬理作用
- GABAの異化を抑制→GABAの濃度↑
- 全ての型のてんかんに作用するが、特に欠神発作によく効く (SPC.187)
注意
- 催奇性有り(催奇形因子)
副作用
- 比較的少ない
- 肝障害
参考
- セレブシロップ５％
- デパケンR錠100／デパケンR錠200
臨床関連
「depakote」
- 同
- Depakene, Depakote, Epival
- 関
- Valproic acid