General
Preferred name
VALPROIC ACID
Synonyms
VALPROATE SODIUM ()
Depakine ()
Valproic acid, sodium salt ()
Acidum valproicum ()
Valproic acid sodium ()
VALPROATE MAGNESIUM ()
Valproate ()
Sodium Valproate ()
Valproate semisodium ()
Epival ()
Valproic acid sodium salt ()
DIVALPROEX SODIUM ()
2-Propylvaleric Acid ()
Valproate bismuth ()
Valproic acid (sodium) ()
MAGNESIUM VALPROATE ()
Dipropylacetic Acid ()
Sodium Valproate (sodium) ()
Valproic Acid (NSC 93819) sodium salt ()
Valproic acid (VPA) ()
Sodium valproate,NSC 93819,2-Propylpentanoic Acid ()
2-Propylvaleric Acid, Valproate ()
Epilim Chronosphere ()
NSC-732626 ()
Selenica ()
A-44090 ()
ABBOTT 44090 ()
Depakote ()
Epilim IV ()
Epilim Chrono 200 ()
Epilim Chrono 300 ()
NSC-757376 ()
KW-6066N ()
Valproic acid, sodium ()
Orlept ()
Valproic acid sodium salt (1:1) ()
Depakote CP ()
Sodium 2-propylpentanoate ()
Delepsine ()
Epilim ()
Epilim 200 ()
Orfiril ()
ABBOTT-44090 ()
Episenta ()
Natrii valproas ()
Depakote Er ()
Epilim 500 ()
Epilim Chrono 500 ()
Kentilim ()
Depacon ()
Valproic acid sodium salt (2:1) ()
Divalproex ()
Semisodium Valproate ()
ABBOTT 50711 ()
ABBOTT-50711 ()
Pentanoic acid, 2-propyl ()
Stavzor ()
Depakene ()
Convulex ()
Valproic acid extended release ()
NSC-93819 ()
44089 ()
Valproic Acid-d4 (sodium salt) ()
Valproic acid (sodium salt) ()
Divalproex (sodium salt) ()
P&D ID
PD003158
CAS
1069-66-5
76584-70-8
99-66-1
62959-43-7
94071-09-7
2749637-13-4
Tags
obsolete probe
drug candidate
natural product
drug
available
Approved by
FDA
First approval
1983
1996
1978
Drug Status
investigational
approved
Drug indication
Alcohol dependence
Discovery agent
Seizure disorder
Anticonvulsant
Epilepsy
Max Phase
Phase 4
Phase 3
Probe control
Probe control not defined
Orthogonal probes
0
No orthogonal probes found
Similar probes
0
No structurally similar probes found
Structure
P&D probe-likeness score
Structure formats
[[ format ]]
[[ compound[format === 'MOL' ? 'molblock' : format.toLowerCase()] ]]
Description
(extracted from source data)
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 Ï, Ï1, and Ï2 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)
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 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)
[[ p.pathway_name ]]
[[ compound.targets[tid].gene_name ]]
Cell lines
1
Organisms
0
Compound Sets
34
AdooQ Bioactive Compound Library
Axon Medchem Screening Library
BOC Sciences Bioactive Compounds
CeMM library of unique drugs (CLOUD)
ChEMBL Approved Drugs
ChEMBL Drugs
Drug Repurposing Hub
DrugCentral
DrugCentral Approved Drugs
DrugMatrix
Enamine BioReference Compounds
Guide to Pharmacology
LINCS compound set
LOPAC library
LSP-MoA library (Laboratory of Systems Pharmacology)
NCATS Inxight Approved Drugs
NIH Clinical Collections (NCC)
Novartis Chemogenetic Library (NIBR MoA Box)
NPC Screening Collection
Obsolete Compounds
Other bioactive compounds
Prestwick Chemical Library
ReFrame library
Selleckchem Bioactive Compound Library
The Spectrum Collection
Tocris Bioactive Compound Library
Tocriscreen Plus
[[ a.name ]]
[[ ligand_id ]]
free of charge
External IDs
122
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
GABAR
HDAC2
HDAC9
HDAC
GABA
Sodium Channel
HDACs
ABAT, ACADSB, ALDH5A1, HDAC1, HDAC2, HDAC9, OGDH, SCN10A, SCN11A, SCN1A, SCN1B, SCN2A, SCN2B, SCN3A, SCN3B, SCN4A, SCN4B, SCN5A, SCN7A, SCN8A, SCN9A
Anti-convulsant
Endogenous Metabolite
HIV
Mitophagy
Notch
Autophagy,GABA Receptor,HDAC,Mitophagy,Notch,PGC-1¦Á
Autophagy,HDAC,Mitophagy,Notch,PGC-1¦Á
Pathway
Chromatin/Epigenetic
Membrane Transporter/Ion Channel
DNA Damage/DNA Repair
Neuroscience
NF-??b
NF-¦ªb
Anti-infection
Apoptosis
Autophagy
Cell Cycle/DNA Damage
Epigenetics
Metabolic Enzyme/Protease
Neuronal Signaling
Stem Cell/Wnt
Primary Target
Non-selective HDACs
Member status
member
Indication
epilepsy, seizures, seizures
Therapeutic Class
Anticonvulsants
Neurology Agents
Solubility
In vitro:<br/>10 mM in DMSO
Source data
