General
Preferred name
VALPROIC ACID
Synonyms
VALPROATE SODIUM ()
Depakine ()
Valproic acid, sodium salt ()
Acidum valproicum ()
Valproic acid sodium ()
VALPROATE MAGNESIUM ()
Valproate ()
Sodium Valproate ()
2-Propylpentanoic Acid ()
VPA ()
2-Propylvaleric Acid ()
Valproate semisodium ()
Epival ()
DIVALPROEX SODIUM ()
Valproic acid sodium salt ()
Valproic acid (sodium) ()
Dipropylacetic Acid ()
VPA (sodium) ()
2-Propylpentanoic acid (sodium) ()
Sodium valproate,NSC 93819,2-Propylpentanoic Acid ()
2-Propylvaleric Acid, Valproate ()
Valproic Acid (NSC 93819) sodium salt ()
Valproic acid (VPA) ()
MAGNESIUM VALPROATE ()
Valproic acid (sodium salt) ()
Valproate bismuth ()
Divalproex (sodium salt) ()
Epilim IV ()
Valproic acid sodium salt (1:1) ()
NSC-757376 ()
KW-6066N ()
Epilim 200 ()
NSC-732626 ()
ABBOTT-44090 ()
ABBOTT 44090 ()
Epilim ()
A-44090 ()
Epilim Chrono 500 ()
Epilim 500 ()
Depacon ()
Sodium 2-propylpentanoate ()
Epilim Chrono 300 ()
Episenta ()
Orfiril ()
Valproic acid, sodium ()
Kentilim ()
Natrii valproas ()
Orlept ()
Epilim Chronosphere ()
Selenica ()
Epilim Chrono 200 ()
Delepsine ()
Valproato semisodico ()
Depakote ()
Semisodium Valproate ()
Valproic acid sodium salt (2:1) ()
Depakote CP ()
Valproate semisodique ()
ABBOTT 50711 ()
Depakote Er ()
Divalproex ()
ABBOTT-50711 ()
NSC-93819 ()
Depakene ()
44089 ()
VALPROIC ACID EXTENDED RELEASE ()
Stavzor ()
ACIDO VALPROICO ()
ACIDE VALPROIQUE ()
Convulex ()
PENTANOIC ACID, 2-PROPYL ()
Dipromal ()
Valproic Acid-d4 ()
P&D ID
PD003158
CAS
1069-66-5
76584-70-8
99-66-1
62959-43-7
94071-09-7
87745-17-3
Tags
available
obsolete probe
drug
drug candidate
Approved by
FDA
First approval
1978
1983
1996
Drug indication
Discovery agent
Alcohol dependence
Seizure disorder
Neoplasm
Seizure
Epilepsy
Drug Status
approved
investigational
Max Phase
3.0
4.0
Structure
Probe scores
P&D probe-likeness score
[[ v.score ]]%
Structure formats
[[ format ]]
[[ compound[format === 'MOL' ? 'molblock' : format.toLowerCase()] ]]
Description
(extracted from source data)
PRICE 29
PRICE 29
METABOLISM Most drug is metabolized to glucuronide conjugates (30-50%) of the parent drug or of metabolites.[Label,A178066] Another large portion is metabolized through mitochondrial β-oxidation (40%). The remainder of metabolism (15-20%) occurs through oxidation, hydroxylation, and dehydrogenation at the ω, ω1, and ω2 positions resulting in the formation of hydroxyls, ketones, carboxyls, a lactone metabolite, double bonds, and combinations.
PHARMACODYNAMICS Valproate has been shown to reduce the incidence of complex partial seizures and migraine headaches.[FDA Label,A177841] It also improves symptom control in bipolar mania.[A178033] Although the exact mechanisms responsible are unknown, it is thought that valproate produces increased cortical inhibition to contribute to control of neural synchrony. It is also thought that valproate exerts a neuroprotective effect preventing damage and neural degeneration in epilepsy, migraines, and bipolar disorder.; ; Valproate is hepatotoxic and teratogenic. The reasons for this are unclear but have been attributed to the genomic effects of the drug.[A457]; ; A small proof-of concept study found that valproate increases clearance of human immunodeficiency virus (HIV) when combined with highly active antiretroviral therapy (HAART) by reactivating the virus to allow clearance, however, a larger multicentre trial failed to show a significant effect on HIV reservoirs when added to HAART.[A458,A177859] The FDA labeling contains a warning regarding HIV reactivation during valproate use.[label].
HALF-LIFE 13-19 hours.[label]; ; The half-life in neonates ranges from 10-67 hours while the half-life in pediatric patients under 2 months of age ranges from 7-13 hours.
INDICATION **Indicated** for:[Label] ; ; 1) Use as monotherapy or adjunctive therapy in the management of complex partial seizures and simple or complex absence seizures. ; ; 2) Adjunctive therapy in the management of multiple seizure types that include absence seizures. ; ; 3) Prophylaxis of migraine headaches.; ; 4) Acute management of mania associated with bipolar disorder.; ; ; **Off-label** uses include:; ; 1) Maintenance therapy for bipolar disorder.[A177919]; ; 2) Treatment for acute bipolar depression.[A177928,A177931,A177934]; ; 3) Emergency treatment of status epilepticus.[A177955]
ROE Most drug is eliminated through hepatic metabolism, about 30-50%.[label] The other major contributing pathway is mitochondrial β-oxidation, about 40%. Other oxidative pathways make up an additional 15-20%. Less than 3% is excreted unchanged in the urine.
TOXICITY **LD50 Values**; ; Oral, mouse: 1098 mg/kg; ; Oral, rat: 670 mg/kg; ; **Overdose**; ; Symptoms of overdose include somnolence, heart block, deep coma, and hypernatremia. Fatalities have been reported, however patients have recovered from valproate serum concentrations as high as 2120 mcg/mL. The unbound fraction may be removed by hemodialysis. Naloxone has been demonstrated to reverse the CNS depressant effects of overdose but may also reverse the anti-epileptic effects.[FDA Label]; ; **Reproductive Toxicity**; ; Valproate use in pregnancy is known to increase the risk of neural tube defects and other structural abnormalities.[FDA Label] The risk of spina bifida increases from 0.06-0.07% in the normal population to 1-2% in valproate users. The North American Antiepileptic Drug (NAAED); Pregnancy Registry reports a major malformation rate of 9-11%, 5 times the baseline rate. These malformations include neural tube defects, cardiovascular malformations, craniofacial defects (e.g., oral clefts, craniosynostosis), hypospadias, limb malformations (e.g., clubfoot, polydactyly), and other malformations of varying severity involving other body systems. Other antiepileptic drugs, lamotrigine, carbemazepine, and phenytoin, have been found to reduce IQ in children exposed in utero. Valproate was also studied however the results did not achieve statistical significance (97 IQ (CI: 94-101)). Observational studies report an absolute risk increase of 2.9% (relative risk 2.9 times baseline) of autism spectrum disorder in children exposed to valproate in utero. There have been case reports of fatal hepatic failure in children of mothers who used valproate during pregnancy.; ; There have been reports of male infertility when taking valproate.[FDA Label]; ; **Lactation**; ; Valproate is excreted in human milk.[FDA Label] Data in the published literature describe the presence of valproate in human milk (range: 0.4 mcg/mL to 3.9 mcg/mL), corresponding to 1% to 10% of maternal serum levels. Valproate serum concentrations collected from breastfed infants aged 3 days postnatal to 12 weeks following delivery ranged from 0.7 mcg/mL to 4 mcg/mL, which were 1% to 6% of maternal serum valproate levels. A published study in children up to six years of age did not report adverse developmental or cognitive effects following exposure to valproate; via breast milk.; ; **Other Toxicity Considerations**; ; Use in pediatrics under 2 years of age increases the risk of fatal hepatotoxicity.[FDA Label];
ABSORPTION The intravenous and oral forms of valproic acid are expected to produce the same AUC, Cmax, and Cmin at steady-state.[label] The oral delayed-release tablet formulation has a Tmax of 4 hours. Differences in absorption rate are expected from other formulations but are not considered to be clinically important in the context of chronic therapy beyond impacting frequency of dosing. Differences in absorption may create earlier Tmax or higher Cmax values on initiation of therapy and may be affected differently by meals.[L6196] The extended release tablet formulation had Tmax increase from 4 hours to 8 hours when taken with food. In comparison, the sprinkle capsule formulation had Tmax increase from 3.3 hours to 4.8 hours. Bioavailability is reported to be approximately 90% with all oral formulations with enteric-coated forms possibly reaching 100%.[A178066]
DESCRIPTION Valproic acid is a fatty acid with anticonvulsant properties. It is commonly administered in a salt preparation, valproate sodium. (GtoPdb)
PRICE 29
DESCRIPTION Protein tyrosine phosphatase inhibitor (Tocris Bioactive Compound Library)
DESCRIPTION Histone deacetylase inhibitor (Tocriscreen Plus)
DESCRIPTION Anticonvulsant (LOPAC library)
DESCRIPTION Valproic acid is a HDAC inhibitor by selectively inducing proteasomal degradation of HDAC2, used in the treatment of epilepsy, bipolar disorder and prevention of migraine headaches. (BOC Sciences Bioactive Compounds)
DESCRIPTION Valproic acid sodium salt (Sodium Valproate) is the sodium salt form of valproic acid with anti-epileptic activity. Valproic acid sodium salt is converted into its active form, valproate ion, in blood. Although the mechanism of action remains to be elucidated, Valproic acid sodium salt increases concentrations of gamma-aminobutyric acid (GABA) in the brain, probably due to inhibition of the enzymes responsible for the catabolism of GABA. This potentiates the synaptic actions of GABA. Valproic acid sodium salt may also affect potassium channels, thereby creating a direct membrane-stabilizing effect. (TargetMol Bioactive Compound Library)
DESCRIPTION Divalproex Sodium (Valproate semisodium) binds to and inhibits gamma-aminobutyric acid (GABA) transaminase and its anticonvulsant activity may be exerted by increasing brain concentration of GABA and by inhibiting enzymes that catabolize GABA or block the reuptake of GABA into glia and nerve endings. It also is an HDAC inhibitor, Comprised of sodium valproate and valproic acid with anticonvulsant and antiepileptic activities. Divalproex may also work by suppressing repetitive neuronal firing through the inhibition of voltage-sensitive sodium channels. (TargetMol Bioactive Compound Library)
DESCRIPTION Valproic acid is an inhibitor of histone deacetylase (HDAC) inhibitor, which has an anticancer effect. Valproic acid was shown to induce proliferation and enhance self-renewal of hematopoietic stem cells (HSC). (BOC Sciences Bioactive Compounds)
DESCRIPTION Valproic acid is a fatty acid derivative and anticonvulsant. It is used to control complex partial seizures and both simple and complex absence seizures. It acts as a direct histone deactylase (HDAC) inhibitor. (Enamine Bioactive Compounds)
DESCRIPTION Valproic Acid (2-Propylpentanoic Acid) is an HDAC inhibitor that inhibits HDAC1 activity, induces HDAC2 degradation, and is orally active. Valproic Acid can be used in epilepsy and bipolar disorder research. (TargetMol Bioactive Compound Library)
Cell lines
5
Organisms
0
Compound Sets
37
AdooQ Bioactive Compound Library
A10321
Axon Medchem Screening Library
3127
BOC Sciences Bioactive Compounds
valproic-acid-sodium-salt-sodium-valproate-cas-1069-66-5-item-84-53920
valproic-acid-cas-99-66-1-item-286120
Cayman Chemical Bioactives
13033
35739
22960
39966
CeMM library of unique drugs (CLOUD)
ChEMBL Approved Drugs
CHEMBL433
CHEMBL2105613
CHEMBL109
ChEMBL Drugs
CHEMBL433
CHEMBL2105613
CHEMBL109
CHEMBL2315212
CZ-OPENSCREEN Bioactive Library
Drug Repurposing Hub
DrugBank
DB00313
DB13910
DrugBank Approved Drugs
DB00313
DB13910
DrugCentral
2803
DrugCentral Approved Drugs
2803
DrugMAP
DMX6PLV
DM4RK0G
DMCFE9I
DrugMAP Approved Drugs
DM4RK0G
DMCFE9I
DrugMatrix
Enamine Bioactive Compounds
EBC-13795
Enamine BioReference Compounds
EUbOPEN Chemogenomics Library
EUB0000833
Guide to Pharmacology
7009
LINCS compound set
10346-110
LOPAC library
LSP-MoA library (Laboratory of Systems Pharmacology)
CHEMBL109
MedChem Express Bioactive Compound Library
HY-10585A
HY-10585
NCATS Inxight Approved Drugs
614OI1Z5WI
NIH Clinical Collections (NCC)
Novartis Chemogenetic Library (NIBR MoA Box)
NPC Screening Collection
Obsolete Compounds
valproic-acid
Other bioactive compounds
Prestwick Chemical Library
ReFrame library
Selleckchem Bioactive Compound Library
Sodium-valproate
Divalproex-sodium
valproic-acid
TargetMol Bioactive Compound Library
T1602
T6474
T7064
The Spectrum Collection
Tocris Bioactive Compound Library
2815
Tocriscreen Plus
2815
External IDs
131
Properties
(calculated by RDKit )
Molecular Weight
144.12
Hydrogen Bond Acceptors
1
Hydrogen Bond Donors
1
Rotatable Bonds
5
Ring Count
0
Aromatic Ring Count
0
cLogP
2.29
TPSA
37.3
Fraction CSP3
0.88
Chiral centers
0.0
Largest ring
0.0
QED
0.64
Structural alerts
1
historic compounds (Chemical Probes.org)
Obsolete
Related compounds
Custom attributes
(extracted from source data)
Target Type
Enzymes
MOA
GABA aminotransferase inhibitor
Inhibitor
GABA Receptor activator
Sodium Channel inhibitor
Histone Deacetylase 1 (HDAC1) Inhibitors
GABAergic Transmission Enhancers
benzodiazepine receptor agonist, HDAC inhibitor
Target
4-aminobutyrate aminotransferase, mitochondrial
Succinate semialdehyde dehydrogenase
GABA Receptor
HDAC
ABAT, ACADSB, ALDH5A1, HDAC1, HDAC2, HDAC9, OGDH, SCN10A, SCN11A, SCN1A, SCN1B, SCN2A, SCN2B, SCN3A, SCN3B, SCN4A, SCN4B, SCN5A, SCN7A, SCN8A, SCN9A
Anti-convulsant
Apoptosis
Endogenous Metabolite
HIV
Mitophagy
Notch
Organoid
Autophagy,GABA Receptor,HDAC,Mitophagy,Notch,PGC-1¦Á
Autophagy,HDAC,Mitophagy,Notch,PGC-1¦Á
GABAR
HDAC2
HDAC9
GABA
HDAC1
HDACs
Sodium Channel
Primary Target
Non-selective HDACs
Pathway
NF-¦ªb
Autophagy
Chromatin/Epigenetic
DNA Damage/DNA Repair
Membrane Transporter/Ion Channel
Microbiology/virology
Neuroscience
Proteases/Proteasome
Stem Cells
Anti-infection
Cell Cycle/DNA Damage
Epigenetics
Metabolic Enzyme/Protease
Neuronal Signaling
Stem Cell/Wnt
Member status
member
Indication
epilepsy, seizures, seizures
Therapeutic Class
Anticonvulsants
Neurology Agents
Solubility
In vitro:<br/>10 mM in DMSO
Recommended Cell Concentration
10 uM
Source data