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Identification
Name Divalproex sodium
Accession Number DB00510 (APRD00066)
Type small molecule
Groups approved
Description

A fatty acid with anticonvulsant properties used in the treatment of epilepsy. The mechanisms of its therapeutic actions are not well understood. It may act by increasing gamma-aminobutyric acid levels in the brain or by altering the properties of voltage dependent sodium channels. [PubChem]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • Divalproex sodium
  • Valproate semisodium
Brand names
  • Depakote
  • Depakote CP
  • Depakote ER
  • Depakote Sprinkle
  • Epival
Brand name mixtures Not Available
Categories
  • Anticonvulsants
  • Antimanic Agents
  • GABA Agents
CAS number 76584-70-8
Weight Average: 310.4047
Monoisotopic: 310.212004155
Chemical Formula C16H31NaO4
InChI Key InChIKey=MSRILKIQRXUYCT-UHFFFAOYSA-M
InChI
InChI=1S/2C8H16O2.Na/c2*1-3-5-7(6-4-2)8(9)10;/h2*7H,3-6H2,1-2H3,(H,9,10);/q;;+1/p-1
Plain Text
IUPAC Name
sodium 2-propylpentanoate 2-propylpentanoic acid
SMILES
[Na+].CCCC(CCC)C(O)=O.CCCC(CCC)C([O-])=O
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Fatty Acids
Substructures
  • Hydroxy Compounds
  • Anions
  • Acetates
  • Carboxylic Acids and Derivatives
  • Cations
  • Fatty Acids
Pharmacology
Indication For treatment and management of seizure disorders, mania, and prophylactic treatment of migraine headache.
Pharmacodynamics Divalproex is a stable co-ordination compound comprised of sodium valproate and valproic acid in a 1:1 molar relationship and formed during the partial neutralization of valproic acid with 0.5 equivalent of sodium hydroxide. Divalproex is an anticonvulsant and mood-stabilizing drug used primarily in the treatment of epilepsy and bipolar disorder. It is also used to treat migraine headaches and schizophrenia. In epileptics, divalproex is used to control absence seizures, tonic-clonic seizures (grand mal), complex partial seizures, and the seizures associated with Lennox-Gastaut syndrome. Divalproex is believed to affect the function of the neurotransmitter GABA (as a GABA transaminase inhibitor) in the human brain. Divalproex dissociates to the valproate ion in the gastrointestinal tract.
Mechanism of action Divalproex binds to and inhibits GABA transaminase. The drug's anticonvulsant activity may be related to increased brain concentrations of gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter in the CNS, by inhibiting enzymes that catabolize GABA or block the reuptake of GABA into glia and nerve endings. Divalproex may also work by suppressing repetitive neuronal firing through inhibition of voltage-sensitive sodium channels.
Absorption Rapid absorption from gastrointestinal tract.
Volume of distribution
  • 11 L/1.73 m2 [total valproate]
  • 92 L/1.73 m2 [free valproate]
Protein binding 80-90%
Metabolism

Divalproex is metabolized almost entirely by the liver. Mitochondrial ß-oxidation is the other major metabolic pathway, typically accounting for over 40% of the dose.
Route of elimination Valproate is metabolized almost entirely by the liver.
Half life 9-16 hours
Clearance Not Available
Toxicity Overdosage with divalproex may result in somnolence,heart block,and deep coma. Fatalities have been reported; however patients have recovered from divalproex levels as high as 2120 µg/mL.
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Abbott laboratories pharmaceutical products div
  • Dr reddys laboratories ltd
  • Zydus pharmaceuticals usa inc
  • Abbott laboratories
  • Anchen pharmaceuticals taiwan inc
  • Lupin ltd
  • Mylan pharmaceuticals inc
  • Nu pharm inc
  • Orchid healthcare
  • Sandoz inc
  • Sun pharmaceutical industries ltd
  • Teva pharmaceuticals usa inc
  • Upsher smith laboratories inc
  • Vintage pharmaceuticals llc
  • Wockhardt ltd
  • Impax laboratories inc
  • Teva pharmaceuticals usa
Packagers
Dosage forms
Form Route Strength
Tablet, delayed release Oral
Prices
Unit description Cost Unit
Depakote 500 mg tablet ec 5.48 USD tablet
Depakote dr 500 mg tablet 4.08 USD tablet
Depakote 500 mg Enteric Coated Tabs 4.01 USD tab
Depakote er 500 mg tablet 3.54 USD tablet
Depakote ER 500 mg 24 Hour tablet 3.36 USD tablet
Divalproex Sodium 500 mg Enteric Coated Tabs 3.34 USD tab
Divalproex sod dr 500 mg tablet 3.25 USD tablet
Divalproex Sodium 500 mg 24 Hour tablet 3.07 USD tablet
Depakote ec 250 mg tablet 2.22 USD tablet
Depakote 250 mg Enteric Coated Tabs 2.17 USD tab
Depakote ER 250 mg 24 Hour tablet 2.05 USD tablet
Depakote er 250 mg tablet 2.02 USD tablet
Divalproex Sodium 250 mg Enteric Coated Tabs 1.81 USD tab
Divalproex sod dr 250 mg tablet 1.76 USD tablet
Divalproex Sodium 250 mg 24 Hour tablet 1.75 USD tablet
Depakote ec 125 mg tablet 1.14 USD tablet
Depakote 125 mg Enteric Coated Tabs 1.11 USD tab
Depakote 125 mg sprinkle capsule 1.09 USD capsule
Depakote Sprinkles 125 mg Sprinkle Capsule 1.05 USD capsule
Epival 500 mg Enteric-Coated Tablet 1.04 USD tablet
Divalproex Sodium 125 mg Enteric Coated Tabs 0.92 USD tab
Divalproex sod dr 125 mg tablet 0.9 USD tablet
Apo-Divalproex 500 mg Enteric-Coated Tablet 0.52 USD tablet
Epival 250 mg Enteric-Coated Tablet 0.52 USD tablet
Mylan-Divalproex 500 mg Enteric-Coated Tablet 0.52 USD tablet
Novo-Divalproex 500 mg Enteric-Coated Tablet 0.52 USD tablet
Nu-Divalproex 500 mg Enteric-Coated Tablet 0.52 USD tablet
Pms-Divalproex 500 mg Enteric-Coated Tablet 0.52 USD tablet
Epival 125 mg Enteric-Coated Tablet 0.29 USD tablet
Apo-Divalproex 250 mg Enteric-Coated Tablet 0.26 USD tablet
Mylan-Divalproex 250 mg Enteric-Coated Tablet 0.26 USD tablet
Novo-Divalproex 250 mg Enteric-Coated Tablet 0.26 USD tablet
Nu-Divalproex 250 mg Enteric-Coated Tablet 0.26 USD tablet
Pms-Divalproex 250 mg Enteric-Coated Tablet 0.26 USD tablet
Apo-Divalproex 125 mg Enteric-Coated Tablet 0.14 USD tablet
Mylan-Divalproex 125 mg Enteric-Coated Tablet 0.14 USD tablet
Novo-Divalproex 125 mg Enteric-Coated Tablet 0.14 USD tablet
Nu-Divalproex 125 mg Enteric-Coated Tablet 0.14 USD tablet
Pms-Divalproex 125 mg Enteric-Coated Tablet 0.14 USD tablet
Patents
Country Patent Number Approved Expires
United States 6511678 1999-06-18 2019-06-18
Properties
State solid
Melting point 222 oC
Experimental Properties
Property Value Source
water solubility Slightly soluble (2000 mg/L) PhysProp
logP 2.549 PhysProp
pKa 4.8 Various sources
Predicted Properties
Property Value Source
water solubility ALOGPS
logP ALOGPS
logP 2.80 ChemAxon Molconvert
logS ALOGPS
pKa ChemAxon Molconvert
hydrogen acceptor count 2 ChemAxon Molconvert
hydrogen donor count 1 ChemAxon Molconvert
polar surface area 37.30 ChemAxon Molconvert
rotatable bond count 10 ChemAxon Molconvert
refractivity 40.25 ChemAxon Molconvert
polarizability 16.98 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference
  1. www.mentalhealth.com Link
External Links
Resource Link
KEGG Drug D00304 Link_out
PubChem Compound 23663956 Link_out
PubChem Substance 46507273 Link_out
ChemSpider 48337 Link_out
ChEBI 4667 Link_out
ChEMBL 4667 Link_out
Therapeutic Targets Database DAP000556 Link_out
PharmGKB PA449377 Link_out
Drug Product Database 2245753 Link_out
RxList http://www.rxlist.com/cgi/generic/dival.htm Link_out
Drugs.com http://www.drugs.com/cdi/divalproex-delayed-release-tablets.html Link_out
PDRhealth http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/dep1125.shtml Link_out
Wikipedia http://en.wikipedia.org/wiki/Divalproex_sodium Link_out
ATC Codes Not Available
AHFS Codes Not Available
PDB Entries
FDA label show (115.6 KB)
MSDS show (77.9 KB)
Interactions
Drug Interactions Not Available
Food Interactions
  • Food slows the rate of absorption but the extent of absorption is not affected.
  • Take with food to reduce irritation.
Targets

1. 4-aminobutyrate aminotransferase, mitochondrial

Pharmacological action: yes
Actions: inhibitor

Catalyzes the conversion of gamma-aminobutyrate and L- beta-aminoisobutyrate to succinate semialdehyde and methylmalonate semialdehyde, respectively. Can also convert delta-aminovalerate and beta-alanine

Organism class: human
UniProt ID: P80404 Link_out
Gene: ABAT Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Loscher W: Basic pharmacology of valproate: a review after 35 years of clinical use for the treatment of epilepsy. CNS Drugs. 2002;16(10):669-94. Pubmed
  2. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  3. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on April 19, 2011 15:04

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.