Drugbank Logo

Showing drug card for Divalproex sodium (DB00510)

Legend: drug field target field enzyme field

for drugs
Version 2.5
Creation Date 2005-06-13 13:24:05
Update Date 2009-04-16 16:47:45
Primary Accession Number DB00510
Secondary Accession Number
  • APRD00066
Name Divalproex sodium
Drug Type
  • Approved
  • Small Molecule
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]
Synonyms
  1. Divalproex sodium
  2. Valproate semisodium
Brand Names
  1. Depakote
  2. Depakote CP
  3. Depakote ER
  4. Depakote Sprinkle
  5. Epival
Brand Mixtures Not Available
Chemical IUPAC Name sodium; 2-propylpentanoate; 2-propylpentanoic acid
Chemical Formula C16H31NaO4
Chemical Structure Structure
CAS Registry Number 76584-70-8
InChI Identifier InChI=1/2C8H16O2.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/fC8H16O2.C8H15O2.Na/h9H;;/q;-1;m
InChI Key MSRILKIQRXUYCT-HKZHNDDDCD
KEGG Drug D00304 Link Image
KEGG Compound Not Available
PubChem Compound 53519 Link Image
PubChem Substance 7847370 Link Image
ChEBI ID Not Available
PharmGKB ID PA449377 Link Image
HET ID Not Available
GenBank ID Not Available
Drug ID Number [DIN] 02245753 Link Image
RxList Link http://www.rxlist.com/cgi/generic/dival.htm Link Image
PDRhealth Link http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/dep1125.shtml Link Image
Wikipedia Link http://en.wikipedia.org/wiki/Divalproex_sodium Link Image
FDA Label
Material Safety Data Sheet (MSDS)
Synthesis Reference Not Available
Average Molecular Weight 310.4047
Monoisotopic Molecular Weight 310.2120
State Solid
Melting Point 222 oC
Experimental Water Solubility Slightly soluble (2000 mg/L) Source: PhysProp
Predicted Water Solubility Not Available Calculated using ALOGPS
Experimental LogP/Hydrophobicity 2.549 Source: PhysProp
Predicted LogP Not Available Calculated using ALOGPS
Experimental LogS Not Available
Predicted LogS Not Available Calculated using ALOGPS
Experimental Caco2 Permeability Not Available
pKa/Isoelectric Point 4.8
Mass Spectrum Not Available
MOL File Show Link Image | Download Link Image
SDF File Show Link Image | Download Link Image
PDB File Show Link Image | Download Link Image
2D Structure
3D Structure
Experimental PDB ID 1OHY Link Image
Experimental PDB File Show
Experimental PDB Structure
Isomeric SMILES [Na+].CCCC(CCC)C(O)=O.CCCC(CCC)C([O-])=O
Canonical SMILES [Na+].CCCC(CCC)C(O)=O.CCCC(CCC)C([O-])=O
Drug Category
  • Anticonvulsants
  • Antimanic Agents
  • GABA Agents
ATC Codes Not Available
AHFS Codes Not Available
Indication For treatment and management of seizure disorders, mania, and prophylactic treatment of migraine headache.
Pharmacology 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.
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.
Protein Binding 80-90%
Biotransformation 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.
Half Life 9-16 hours
Dosage Forms
Form Route
Tablet, delayed release Oral
Patient Information Show Link Image
Contraindications Show Link Image
Interactions Show Link Image
Drug Interactions
Drug Interaction
Amobarbital Valproic acid increases the effect of barbiturate
Aprobarbital Valproic acid increases the effect of barbiturate
Aspirin The salicylate increases the effect of valproic acid
Bismuth Subsalicylate The salicylate increases the effect of valproic acid
Butabarbital Valproic acid increases the effect of barbiturate
Butalbital Valproic acid increases the effect of barbiturate
Butethal Valproic acid increases the effect of barbiturate
Carbamazepine Carbamazepine decreases the effect of valproic acid
Cholestyramine Cholestyramine decreases the levels of valproate
Cisplatin Possible decrease of anticonvulsant levels
Dihydroquinidine barbiturate Valproic acid increases the effect of barbiturate
Erythromycin Erythromycin increases the effect of valproic acid
Ethotoin Valproate increases the effect of hydantoin
Felbamate Felbamate increases the effect of valproate
Fosphenytoin Valproate increases the effect of hydantoin
Heptabarbital Valproic acid increases the effect of barbiturate
Hexobarbital Valproic acid increases the effect of barbiturate
Josamycin Erythromycin increases the effect of valproic acid
Lamotrigine Valproic acid increases the effect of lamotrigine
Mephenytoin Valproate increases the effect of hydantoin
Meropenem Decreased plasma antiepileptic levels
Methohexital Valproic acid increases the effect of barbiturate
Methylphenobarbital Valproic acid increases the effect of barbiturate
Nimodipine Valproic acid increases the effect of nimodipine
Pentobarbital Valproic acid increases the effect of barbiturate
Phenobarbital Valproic acid increases the effect of barbiturate
Phenytoin Valproate increases the effect of hydantoin
Primidone Valproic acid increases the effect of barbiturate
Quinidine barbiturate Valproic acid increases the effect of barbiturate
Risperidone Risperidone increases the effect and toxicity of valproic acid
Ritonavir Possible decrease of valproate levels
Salicylate-magnesium The salicylate increases the effect of valproic acid
Salicylate-sodium The salicylate increases the effect of valproic acid
Salsalate The salicylate increases the effect of valproic acid
Secobarbital Valproic acid increases the effect of barbiturate
Talbutal Valproic acid increases the effect of barbiturate
Trisalicylate-choline The salicylate increases the effect of valproic acid
Food Interactions
  • Food slows the rate of absorption but the extent of absorption is not affected.
  • Take with food to reduce irritation.
Pathways Not Available
General References
  1. Drugs.com Link Image
  2. [PubMed Link Image]
  3. Wikipedia Link Image
  4. RxList Link Image
  5. PDRhealth Link Image
Organisms Affected
  • Humans and other mammals
Targets
  1. 4-aminobutyrate aminotransferase, mitochondrial
Drug Target 1 [top]
Target 1 ID 280
Target 1 Name 4-aminobutyrate aminotransferase, mitochondrial
Target 1 Synonyms
  1. (S)-3-amino-2-methylpropionate transaminase
  2. 4-aminobutyrate aminotransferase, mitochondrial precursor
  3. EC 2.6.1.19
  4. EC 2.6.1.22
  5. GABA aminotransferase
  6. GABA transaminase
  7. GABA-AT
  8. GABA-T
  9. Gamma-amino-N-butyrate transaminase
  10. L-AIBAT
Target 1 Gene Name ABAT
Target 1 Protein Sequence >4-aminobutyrate aminotransferase, mitochondrial precursor 
MASMLLAQRLACSFQHSYRLLVPGSRHISQAAAKVDVEFDYDGPLMKTEVPGPRSQELMK
QLNIIQNAEAVHFFCNYEESRGNYLVDVDGNRMLDLYSQISSVPIGYSHPALLKLIQQPQ
NASMFVNRPALGILPPENFVEKLRQSLLSVAPKGMSQLITMACGSCSNENALKTIFMWYR
SKERGQRGFSQEELETCMINQAPGCPDYSILSFMGAFHGRTMGCLATTHSKAIHKIDIPS
FDWPIAPFPRLKYPLEEFVKENQQEEARCLEEVEDLIVKYRKKKKTVAGIIVEPIQSEGG
DNHASDDFFRKLRDIARKHGCAFLVDEVQTGGGCTGKFWAHEHWGLDDPADVMTFSKKMM
TGGFFHKEEFRPNAPYRIFNTWLGDPSKNLLLAEVINIIKREDLLNNAAHAGKALLTGLL
DLQARYPQFISRVRGRGTFCSFDTPDDSIRNKLILIARNKGVVLGGCGDKSIRFRPTLVF
RDHHAHLFLNIFSDILADFK
Target 1 Number of Residues 508
Target 1 Molecular Weight 56440
Target 1 Theoretical pI 8.04
Target 1 GO Classification
Function
4-aminobutyrate transaminase activity
binding
vitamin binding
pyridoxal phosphate binding
catalytic activity
transferase activity
transferase activity, transferring nitrogenous groups
transaminase activity
Process
physiological process
metabolism
cellular metabolism
amino acid and derivative metabolism
amino acid derivative metabolism
gamma-aminobutyric acid metabolism
Component
Not Available
Target 1 General Function Amino acid transport and metabolism
Target 1 Specific Function 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
Target 1 Pathways
Name SMPDB Link KEGG Link
Valine, leucine and isoleucine degradation SMP00032 Link Image map00280 Link Image
Target 1 Reactions
  • 4-aminobutanoate + 2-oxoglutarate = succinate semialdehyde + L-glutamate
Target 1 Pfam Domain Function
Target 1 Signals
  • None
Target 1 Transmembrane Regions
  • None
Target 1 Essentiality Non-Essential
Target 1 GenBank ID Protein 602705 Link Image
Target 1 UniProtKB/Swiss-Prot ID P80404 Link Image
Target 1 UniProtKB/Swiss-Prot Entry Name GABT_HUMAN Link Image
Target 1 PDB ID 1OHY Link Image
Target 1 PDB File Show
Target 1 3D Structure
Target 1 Cellular Location
  • Mitochondrion
  • mitochondrial matrix
Target 1 Gene Sequence >1503 bp 
ATGGCCTCCATGTTGCTCGCCCAGCGGCTGGCCTGCAGCTTCCAGCACACGTACCGCCTG
CTGGTGCCTGGATCCAGACACATTAGTCAAGCTGCAGCCAAAGTCGACGTTGAATTTGAT
TATGATGGGCCTCTGATGAAGACGGAAGTCCCAGGGCCTAGATCTCAGGAGTTAATGAAA
CAGCTGAATATAATTCAGAATGCAGAGGCTGTGCATTTTTTCTGCAATTACGAAGAGAGC
CGAGGCAATTACCTGGTTGATGTGGACGGCAACCGAATGCTGGATCTTTATTCCCAGATC
TCCTCTGTTCCCATAGGTTACAGCGACCCGGCCCTCGTGAAACTCATCCAACAGCCACAA
AATGCGAGCATGTTTGTCAACAGACCCGCCCTCGAAATCCTGCCTCCGGAGAACTTTGTG
GAGAAGCTCCGGCAGTCCTTGCTCTCGGTGGCTCCCAAAGGGATGTCCCAGCTCATCACC
ATGGCCTGCGGCTCCTGCTCCAATGAAAACGCCTTAAAGACCATCTTCATGTGGTACCGG
AGCAAGGAAAGAGGGCAGAGGGGATTCTCCAAAGAGGAGCTGGAGACGTGCATGATTAAC
CAGGCCCCCTGGTGCCCCGACTACAGCATCCTCTCCTTCATGGGTTCCTTCCATGGGAGG
ACCATGGGTTGCTTAGCGACCACGCACTCTAAAGCCATTCACAAGATCGATATCCCTTCC
TTTGACTGGCCCATCGCACCGTTCCCACGGCTGAAATACCCTCTGGAAGAGTTTGTGAAA
GAGAACCAACAGGAAGAGGCCGGCTGTCTGGAAGAGGTTGAGGATCTGATTGTGAAATAT
CGAAAAAAGAAGAAGACGGTGGCCGGGATCATCGTGGAGCCCATCCAGTCCGAGGGTGGA
GACAACCATGCATCCGATGACTTCTTTCGGAAGCTGAGAGACATCGCCAGGAAGCACTGC
TGCGCCTTCTTGGTGGACGAGGTCCAGACCGGAGGAGGCTGCACGGGCAAGTTCTGGGCC
CATGAGCACTGGGGCCTGGATGACCCAGCAGACGTGATGACCTTCAGCAAGAAGATGATG
ACTGGGGGCTTCTTCCTCAAGGAGGAGTTCAGGCCTAATGCTCCCTACCGGATCTTCAAC
ACGTGGCTGGGGGACCCGTCCAAGAACCTGTTGCTGGCTGAGGTCATCAACATCATCAAG
CGGGAGGACCTGCTAAATAATGCAGCCCATGCCGGGAAGGCCCTGCTCACAGGACTGCTG
GACCTCCAGGCCCGGTACCCCCAGTTCATCAGCAGGGTGAGAGGACGAGGCACCTTTTGC
TCCTTCGATACTCCCGATGATTCCATACGGAATAAGCTCATTTTAATTGCCAGAAACAAA
GGTGTGGTGTTGGGTGGCTGTGGTGACAAATCCATTCGTTTCCGTCCCACGCTGGTGTTC
AGGGATCACCACGCTCACCTGTTCCTCAATATTTTCAGTGACATCTTAGCAGACTTCAAG
TAA
Target 1 GenBank Gene ID
Target 1 GeneCard ID ABAT Link Image
Target 1 GenAtlas ID ABAT Link Image
Target 1 HGNC ID HGNC:23 Link Image
Target 1 Chromosome Location 16
Target 1 Locus 16p13.2
Target 1 SNPs SNPJam Report Link Image
Target 1 General References
  1. Medina-Kauwe LK, Tobin AJ, De Meirleir L, Jaeken J, Jakobs C, Nyhan WL, Gibson KM: 4-Aminobutyrate aminotransferase (GABA-transaminase) deficiency. J Inherit Metab Dis. 1999 Jun;22(4):414-27. [PubMed Link Image]
  2. Osei YD, Churchich JE: Screening and sequence determination of a cDNA encoding the human brain 4-aminobutyrate aminotransferase. Gene. 1995 Apr 3;155(2):185-7. [PubMed Link Image]
  3. De Biase D, Barra D, Simmaco M, John RA, Bossa F: Primary structure and tissue distribution of human 4-aminobutyrate aminotransferase. Eur J Biochem. 1995 Jan 15;227(1-2):476-80. [PubMed Link Image]
Target 1 Drug References
  1. 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 Link Image]
  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 Link Image]

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.