U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ACHIRAL
Molecular Formula C8H16O2
Molecular Weight 144.2114
Optical Activity UNSPECIFIED
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of VALPROIC ACID

SMILES

CCCC(CCC)C(O)=O

InChI

InChIKey=NIJJYAXOARWZEE-UHFFFAOYSA-N
InChI=1S/C8H16O2/c1-3-5-7(6-4-2)8(9)10/h7H,3-6H2,1-2H3,(H,9,10)

HIDE SMILES / InChI

Molecular Formula C8H16O2
Molecular Weight 144.2114
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description

Valproic acid (VPA; valproate; di-n-propylacetic acid, DPA; 2-propylpentanoic acid, or 2-propylvaleric acid) was first synthesized in 1882, by Burton. FDA approved valproic acid for the treatment of manic episodes associated with bipolar disorder, for the monotherapy and adjunctive therapy of complex partial seizures and simple and complex absence seizures and adjunctive therapy in patients with multiple seizure types that include absence seizures and for the prophylaxis of migraine headaches. The mechanisms of VPA which seem to be of clinical importance in the treatment of epilepsy include increased gamma-aminobutyric acid (GABA)-ergic activity, reduction in excitatory neurotransmission, and modification of monoamines. Recently, it was discovered that the VPA is a class I selective histone deacetylase inhibitor. This activity can be distinguished from its therapeutically exploited antiepileptic activity.

CNS Activity

Originator

Approval Year

PubMed

PubMed

TitleDatePubMed
Valproate and other anticonvulsants for psychiatric disorders.
2000 Dec 11
[Lyell syndrome associated with lamotrigine].
2000 Dec 16-31
In vivo study of the effect of valpromide and valnoctamide in the pilocarpine rat model of focal epilepsy.
2000 Nov
A case of pharmacokinetic interference in comedication of clozapine and valproic acid.
2000 Nov
Valproate-induced tinnitus misinterpreted as psychotic symptoms.
2000 Oct
[Dementia and extrapyramidal problems caused by long-term valproic acid].
2000 Sep-Oct
Action of valproic acid on Xenopus laevis development: teratogenic effects on eyes.
2001
Benzodiazepines and anticonvulsants for social phobia (social anxiety disorder).
2001
Comparison the cognitive effect of anti-epileptic drugs in seizure-free children with epilepsy before and after drug withdrawal.
2001 Apr
Valproate, but not lamotrigine, induces ovarian morphological changes in Wistar rats.
2001 Feb
Treatment and management of cluster headache.
2001 Feb
The use of baclofen in cluster headache.
2001 Feb
Distribution of valproate to subdural cerebrospinal fluid, subcutaneous extracellular fluid, and plasma in humans: a microdialysis study.
2001 Feb
Antiepileptic drug withdrawal in patients with temporal lobe epilepsy undergoing presurgical video-EEG monitoring.
2001 Feb
A case of chronic pancreatic insufficiency due to valproic acid in a child.
2001 Feb
Recommendations for the management of behavioral and psychological symptoms of dementia.
2001 Feb
[Treatment of cluster headache].
2001 Feb
Glutamate receptor antagonists differentially affect the protective activity of conventional antiepileptics against amygdala-kindled seizures in rats.
2001 Feb
Treatment of impulsivity and aggression in a patient with vascular dementia.
2001 Feb
Melt pelletization of a hygroscopic drug in a high shear mixer. Part 3. Effects of binder variation.
2001 Feb
Effect of coadministered drugs and ethanol on the binding of therapeutic drugs to human serum in vitro.
2001 Feb
Divalproex sodium augmentation of haloperidol in hospitalized patients with schizophrenia: clinical and economic implications.
2001 Feb
Rufinamide: a double-blind, placebo-controlled proof of principle trial in patients with epilepsy.
2001 Feb
Different control of GH secretion by gamma-amino- and gamma-hydroxy-butyric acid in 4-year abstinent alcoholics.
2001 Feb 1
Independent short-term variability of spike-like (600 Hz) and postsynaptic (N20) cerebral SEP components.
2001 Feb 12
[Maintenance dose requirement for phenytoin is lowered in genetically impaired drug metabolism independent of concommitant use of other antiepileptics].
2001 Feb 17
[Febrile convulsions, Treatment and prognosis].
2001 Feb 19
The impact of pharmacogenetics for migraine.
2001 Feb 9
Valproic acid has temporal variability in urinary clearance of metabolites.
2001 Jan
Pharmacologic treatment of patients hospitalized with the diagnosis of schizoaffective disorder.
2001 Jan
Electrophysiological and pharmacological properties of the human brain type IIA Na+ channel expressed in a stable mammalian cell line.
2001 Jan
Evaluating the tolerability of the newer mood stabilizers.
2001 Jan
Contribution of sodium valproate to the syndrome of inappropriate secretion of antidiuretic hormone.
2001 Jan
Clozapine therapy for a patient with a history of Hodgkin's disease.
2001 Jan
Effects of antiepileptic drugs on rat platelet aggregation: ex vivo and in vitro study.
2001 Jan
Occurrence of thrombocytopenia in psychiatric patients taking valproate.
2001 Jan
Additional educational needs in children born to mothers with epilepsy.
2001 Jan
Valproic acid embryopathy: report of two siblings with further expansion of the phenotypic abnormalities and a review of the literature.
2001 Jan 15
[Febrile pleuropericarditis during valproic acid treatment].
2001 Jan 20
Weight change associated with valproate and lamotrigine monotherapy in patients with epilepsy.
2001 Jan 23
A 25-year-old woman with bipolar disorder.
2001 Jan 24-31
Hypothermia and thermoregulatory derangements induced by valproic acid.
2001 Jan 9
Reproductive effects of valproate, carbamazepine, and oxcarbazepine in men with epilepsy.
2001 Jan 9
Mood stabilizers and ion regulation.
2001 Jan-Feb
Does genomic imprinting contribute to valproic acid teratogenicity?
2001 Jan-Feb
Mood-stabilisers reduce the risk of developing antidepressant-induced maniform states in acute treatment of bipolar I depressed patients.
2001 Mar
Naltrexone as a treatment of self-injurious behavior--a case report.
2001 Mar
A phase II study to establish the efficacy and toxicity of sodium valproate in patients with cancer-related neuropathic pain.
2001 Mar
Synthesis and intramitochondrial levels of valproyl-coenzyme A metabolites.
2001 Mar 1
Placebo-controlled study of divalproex sodium for agitation in dementia.
2001 Winter
Patents

Sample Use Guides

In Vivo Use Guide
Usual Adult Dose for Epilepsy Complex partial seizures: Initial dose: 10 to 15 mg/kg orally or intravenously per day as an IV infusion in divided doses, increased by 5 to 10 mg/kg per week if necessary according to clinical response Maintenance dose: 10 to 60 mg/kg per day in divided doses Maximum dose: 60 mg/kg per day Simple and complex absence seizures: Initial dose: 15 mg/kg orally or intravenously per day as an IV infusion in divided doses, increased at one week intervals by 5 to 10 mg/kg/day according to seizure control and tolerability Maximum dose: 60 mg/kg per day Comments: -If the total daily dose exceeds 250 mg, it should be given in 2 to 3 divided doses. -Use of IV valproate sodium for periods longer than 14 days has not been studied; patients should be converted to oral valproate as soon as clinically feasible. -When switching from oral to IV valproate, the total daily dose of IV valproate should be equivalent to the total daily dose of oral valproate, and administered at the same frequency as the oral product. -Equivalence between IV and oral valproate products at steady state has only been evaluated in a 6-hourly dosing regimen. Trough plasma level monitoring may be required if IV valproate is administered 2 to 3 times a day. -Complex partial seizures: When converting patients to valproate monotherapy, concomitant antiepileptic drug dosage can generally be reduced by approximately 25% every 2 weeks, commencing either at the start of valproate therapy or delayed by 1 to 2 weeks. Patients should be monitored closely during this period for increased seizure frequency. Uses: Monotherapy and adjunctive therapy in the treatment of complex partial seizures; sole and adjunctive therapy for simple and complex absence seizures; adjunctive therapy in patients with multiple seizure types that include absence seizures. Usual Adult Dose for Mania Delayed-release capsules : Initial dose: 750 mg orally per day in divided doses Maximum dose: 60 mg/kg orally per day Duration: Safety and efficacy beyond 3 weeks has not been established Comments: -The dose should be increased as rapidly as possible to achieve the lowest therapeutic dose which produces the desired clinical effect or the desired range of plasma concentrations. -In placebo-controlled clinical trials of acute mania, patients were dosed to a clinical response with a trough plasma concentration of 50 to 125 mcg/mL. -Maximum concentrations were generally achieved within 14 days. -Safety and efficacy for longer term use in the maintenance of the initial response and prevention of new manic episodes has not been systematically evaluated in clinical trials. Use for extended periods should be accompanied by regular review for the long-term usefulness of the drug for the individual patient. Use: Treatment of manic episodes associated with bipolar disorder. Usual Adult Dose for Migraine Prophylaxis Delayed release oral capsules: Initial dose: 250 mg orally twice a day Comments: -Some patients may benefit from doses up to 1000 mg per day. -In clinical trials, there was no evidence that higher doses led to greater efficacy. Usual Pediatric Dose for Epilepsy 10 years of age or older: Complex partial seizures: Initial dose: 10 to 15 mg/kg orally or intravenously per day as an IV infusion in divided doses, increased by 5 to 10 mg/kg per week if necessary according to clinical response Maintenance dose: 10 to 60 mg/kg per day in divided doses Maximum dose: 60 mg/kg per day Simple and complex absence seizures: Initial dose: 15 mg/kg orally or intravenously per day as an IV infusion in divided doses, increased at one week intervals by 5 to 10 mg/kg/day according to seizure control and tolerability Maximum dose: 60 mg/kg per day Comments: -If the total daily dose exceeds 250 mg, it should be given in 2 to 3 divided doses. -Use of IV valproate sodium for periods longer than 14 days has not been studied; patients should be converted to oral valproate as soon as clinically feasible. -When switching from oral to IV valproate, the total daily dose of IV valproate should be equivalent to the total daily dose of oral valproate, and administered at the same frequency as the oral product. -Equivalence between IV and oral valproate products at steady state has only been evaluated in a 6-hourly dosing regimen. Trough plasma level monitoring may be required if IV valproate is administered 2 to 3 times a day. -Complex partial seizures: When converting patients to valproate monotherapy, concomitant antiepileptic drug dosage can generally be reduced by approximately 25% every 2 weeks, commencing either at the start of valproate therapy or delayed by 1 to 2 weeks. Patients should be monitored closely during this period for increased seizure frequency. Uses: Monotherapy and adjunctive therapy in the treatment of complex partial seizures; sole and adjunctive therapy for simple and complex absence seizures; adjunctive therapy in patients with multiple seizure types that include absence seizures.
Route of Administration: oral, intravenous
In Vitro Use Guide
H9C2 cells were cultured and allotted to the blank, vehicle, and valproic acid (VPA)-treated groups: the VPA treated group received VPA exposure at concentrations of 2.0, 4.0 and 8.0 mmol/L. VPA might result in acetylation/deacetylation imbalances by inhibiting HDAC1-3 protein expression and total HDAC activity, leading to the down-regulation of mRNA and protein expression of Vangl2 and Scrib.
Substance Class Chemical
Created
by admin
on Mon Oct 21 20:54:45 UTC 2019
Edited
by admin
on Mon Oct 21 20:54:45 UTC 2019
Record UNII
614OI1Z5WI
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
VALPROIC ACID
EP   HSDB   INN   MART.   MI   ORANGE BOOK   USAN   USP   USP-RS   VANDF   WHO-DD  
USAN   INN  
Official Name English
VALPROIC ACID [MI]
Common Name English
VALPROIC ACID [VANDF]
Common Name English
VALPROIC ACID [USP]
Common Name English
DEPAKENE
Brand Name English
PENTANOIC ACID, 2-PROPYL
Common Name English
VALPROIC ACID [WHO-DD]
Common Name English
44089
Code English
VALPROIC ACID [USP-RS]
Common Name English
VALPROATE
Systematic Name English
VALPROIC ACID [ORANGE BOOK]
Common Name English
VALPROIC ACID [HSDB]
Common Name English
PROPYLVALERIC ACID
Systematic Name English
VALPROIC ACID [EP]
Common Name English
VALPROIC ACID EXTENDED RELEASE
Common Name English
VALPROIC ACID [INN]
Common Name English
VALPROIC ACID [MART.]
Common Name English
VALPROIC ACID [USAN]
Common Name English
NSC-93819
Code English
Classification Tree Code System Code
LIVERTOX 1017
Created by admin on Mon Oct 21 20:54:45 UTC 2019 , Edited by admin on Mon Oct 21 20:54:45 UTC 2019
FDA ORPHAN DRUG 563116
Created by admin on Mon Oct 21 20:54:45 UTC 2019 , Edited by admin on Mon Oct 21 20:54:45 UTC 2019
FDA ORPHAN DRUG 256908
Created by admin on Mon Oct 21 20:54:45 UTC 2019 , Edited by admin on Mon Oct 21 20:54:45 UTC 2019
WHO-ESSENTIAL MEDICINES LIST 05
Created by admin on Mon Oct 21 20:54:45 UTC 2019 , Edited by admin on Mon Oct 21 20:54:45 UTC 2019
WHO-ATC N03AG01
Created by admin on Mon Oct 21 20:54:45 UTC 2019 , Edited by admin on Mon Oct 21 20:54:45 UTC 2019
WHO-VATC QN03AG01
Created by admin on Mon Oct 21 20:54:45 UTC 2019 , Edited by admin on Mon Oct 21 20:54:45 UTC 2019
WHO-ESSENTIAL MEDICINES LIST 24.2.2
Created by admin on Mon Oct 21 20:54:45 UTC 2019 , Edited by admin on Mon Oct 21 20:54:45 UTC 2019
NCI_THESAURUS C264
Created by admin on Mon Oct 21 20:54:45 UTC 2019 , Edited by admin on Mon Oct 21 20:54:45 UTC 2019
EU-Orphan Drug EU/3/16/1792
Created by admin on Mon Oct 21 20:54:45 UTC 2019 , Edited by admin on Mon Oct 21 20:54:45 UTC 2019
NDF-RT N0000175751
Created by admin on Mon Oct 21 20:54:45 UTC 2019 , Edited by admin on Mon Oct 21 20:54:45 UTC 2019
NDF-RT N0000175753
Created by admin on Mon Oct 21 20:54:45 UTC 2019 , Edited by admin on Mon Oct 21 20:54:45 UTC 2019
NDF-RT N0000008486
Created by admin on Mon Oct 21 20:54:45 UTC 2019 , Edited by admin on Mon Oct 21 20:54:45 UTC 2019
Code System Code Type Description
EPA CompTox
99-66-1
Created by admin on Mon Oct 21 20:54:45 UTC 2019 , Edited by admin on Mon Oct 21 20:54:45 UTC 2019
PRIMARY
LactMed
99-66-1
Created by admin on Mon Oct 21 20:54:45 UTC 2019 , Edited by admin on Mon Oct 21 20:54:45 UTC 2019
PRIMARY
HSDB
99-66-1
Created by admin on Mon Oct 21 20:54:45 UTC 2019 , Edited by admin on Mon Oct 21 20:54:45 UTC 2019
PRIMARY
NCI_THESAURUS
C29536
Created by admin on Mon Oct 21 20:54:45 UTC 2019 , Edited by admin on Mon Oct 21 20:54:45 UTC 2019
PRIMARY
EVMPD
SUB00015MIG
Created by admin on Mon Oct 21 20:54:45 UTC 2019 , Edited by admin on Mon Oct 21 20:54:45 UTC 2019
PRIMARY
RXCUI
11118
Created by admin on Mon Oct 21 20:54:45 UTC 2019 , Edited by admin on Mon Oct 21 20:54:45 UTC 2019
PRIMARY
IUPHAR
7009
Created by admin on Mon Oct 21 20:54:45 UTC 2019 , Edited by admin on Mon Oct 21 20:54:45 UTC 2019
PRIMARY
RXCUI
40254
Created by admin on Mon Oct 21 20:54:45 UTC 2019 , Edited by admin on Mon Oct 21 20:54:45 UTC 2019
ALTERNATIVE
PUBCHEM
3121
Created by admin on Mon Oct 21 20:54:45 UTC 2019 , Edited by admin on Mon Oct 21 20:54:45 UTC 2019
PRIMARY
CAS
99-66-1
Created by admin on Mon Oct 21 20:54:45 UTC 2019 , Edited by admin on Mon Oct 21 20:54:45 UTC 2019
PRIMARY
ChEMBL
CHEMBL109
Created by admin on Mon Oct 21 20:54:45 UTC 2019 , Edited by admin on Mon Oct 21 20:54:45 UTC 2019
PRIMARY
INN
3300
Created by admin on Mon Oct 21 20:54:45 UTC 2019 , Edited by admin on Mon Oct 21 20:54:45 UTC 2019
PRIMARY
ECHA (EC/EINECS)
202-777-3
Created by admin on Mon Oct 21 20:54:45 UTC 2019 , Edited by admin on Mon Oct 21 20:54:45 UTC 2019
PRIMARY
MERCK INDEX
M11369
Created by admin on Mon Oct 21 20:54:45 UTC 2019 , Edited by admin on Mon Oct 21 20:54:45 UTC 2019
PRIMARY Merck Index
DRUG BANK
DB00313
Created by admin on Mon Oct 21 20:54:45 UTC 2019 , Edited by admin on Mon Oct 21 20:54:45 UTC 2019
PRIMARY
MESH
D014635
Created by admin on Mon Oct 21 20:54:45 UTC 2019 , Edited by admin on Mon Oct 21 20:54:45 UTC 2019
PRIMARY
WIKIPEDIA
VALPROIC ACID
Created by admin on Mon Oct 21 20:54:45 UTC 2019 , Edited by admin on Mon Oct 21 20:54:45 UTC 2019
PRIMARY
Related Record Type Details
TARGET -> INHIBITOR
In vitro studies have shown that VPA is a potent inhibitor of SSA-DH. In brain homogenates, GABA-T is inhibited at high concentrations only. VPA increases GABA levels probably by increasing succinic semialdehyde, a good endogenous inhibitor of GABA-T. Evidence has emerged that valproate exerts a direct effect on excitable membranes and also attenuates the NMDA receptor channel.
COMPETITIVE INHIBITOR
IC50
METABOLIC ENZYME -> SUBSTRATE
MAJOR
SALT/SOLVATE -> PARENT
SALT/SOLVATE -> PARENT
METABOLIC ENZYME -> SUBSTRATE
SALT/SOLVATE -> PARENT
BINDER->LIGAND
METABOLIC ENZYME -> SUBSTRATE
MINOR
SALT/SOLVATE -> PARENT
METABOLIC ENZYME -> SUBSTRATE
SALT/SOLVATE -> PARENT
BASIS OF STRENGTH->SUBSTANCE
ASSAY (HPLC)
USP
BASIS OF STRENGTH->SUBSTANCE
ASSAY (TITRATION)
EP
Related Record Type Details
METABOLITE -> PARENT
MAJOR
URINE
METABOLITE TOXIC -> PARENT
MINOR
URINE
METABOLITE -> PARENT
METABOLITE -> PARENT
contributes partially
MINOR
URINE
METABOLITE -> PARENT
REDUCED IN THE PRESENCE OF ASA
MAJOR
URINE
PRODRUG -> METABOLITE ACTIVE
Related Record Type Details
IMPURITY -> PARENT
UNSPECIFIED
EP
IMPURITY -> PARENT
UNSPECIFIED
EP
IMPURITY -> PARENT
UNSPECIFIED
EP
IMPURITY -> PARENT
UNSPECIFIED
EP
IMPURITY -> PARENT
UNSPECIFIED
EP
IMPURITY -> PARENT
UNSPECIFIED
EP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
UNSPECIFIED
EP
IMPURITY -> PARENT
UNSPECIFIED
EP
IMPURITY -> PARENT
UNSPECIFIED
EP
IMPURITY -> PARENT
UNSPECIFIED
EP
IMPURITY -> PARENT
UNSPECIFIED
EP
Related Record Type Details
ACTIVE MOIETY