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Identification
Name Vigabatrin
Accession Number DB01080 (APRD00282)
Type small molecule
Groups approved
Description

An analogue of gamma-aminobutyric acid. It is an irreversible inhibitor of 4-aminobutyrate transaminase, the enzyme responsible for the catabolism of gamma-aminobutyric acid. (From Martindale The Extra Pharmacopoeia, 31st ed)
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms Not Available
Brand names
  • 4-Amino-5-hexenoic acid
  • 4-Aminohexenoic acid
  • gamma-Vinyl GABA
  • GVG
  • Sabril (TN)
  • Vigabatrin [USAN:BAN:INN]
  • Vigabatrina [Spanish]
  • Vigabatrine
  • Vigabatrine [French]
  • Vigabatrinum [Latin]
Brand name mixtures Not Available
Categories
  • Anticonvulsants
  • Enzyme Inhibitors
  • GABA Agents
CAS number 60643-86-9
Weight Average: 129.157
Monoisotopic: 129.078978601
Chemical Formula C6H11NO2
InChI Key InChIKey=PJDFLNIOAUIZSL-UHFFFAOYSA-N
InChI
InChI=1S/C6H11NO2/c1-2-5(7)3-4-6(8)9/h2,5H,1,3-4,7H2,(H,8,9)
Plain Text
IUPAC Name
4-aminohex-5-enoic acid
SMILES
NC(CCC(O)=O)C=C
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Amino Acids
Substructures
  • Amino Acids
  • Hydroxy Compounds
  • Alkanes and Alkenes
  • Acetates
  • Aliphatic and Aryl Amines
  • Carboxylic Acids and Derivatives
Pharmacology
Indication For use as an adjunctive treatment (with other drugs) in treatment resistant epilepsy, complex partial seizures, secondary generalized seizures, and for monotherapy use in infantile spasms in West syndrome.
Pharmacodynamics Vigabatrin, is an anticonvulsant chemically unrelated to other anticonvulsants. Vigabatrin inhibits the catabolism of GABA. It is an analog of GABA, but it is not a receptor agonist. Vigabatrin irreversibly inhibits the enzyme GABA transaminase.
Mechanism of action It is believed that vigabatrin increases brain concentrations of gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter in the CNS, by irreversibly inhibiting enzymes that catabolize GABA (gamma-aminobutyric acid transaminase GABA-T) or block the reuptake of GABA into glia and nerve endings. Vigabatrin may also work by suppressing repetitive neuronal firing through inhibition of voltage-sensitive sodium channels.
Absorption Rapidly absorbed following oral administration. Food may slightly decrease the rate, but not the extent, of absorption.
Volume of distribution
  • 1.1 L/kg
Protein binding Little to none
Metabolism

Almost no metabolic transformation. Does not induce the hepatic cytochrome P450 system.
Route of elimination Vigabatrin is not significantly metabolized; it is eliminated primarily through renal excretion.
Half life 5-8 hours in young adults, 12-13 hours in elderly.
Clearance
  • 2.4 +/- 0.8 L/h [Infant]
  • 5.7 +/- 2.5 L/h [Children]
Toxicity Not Available
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Lundbeck inc
Packagers
Dosage forms
Form Route Strength
Powder Oral
Tablet Oral
Prices
Unit description Cost Unit
Sabril 500 mg tablet 16.66 USD tablet
Sabril 500 mg Powder Packet 0.95 USD packet
Patents Not Available
Properties
State solid
Melting point Not Available
Experimental Properties
Property Value Source
water solubility 55.1 mg/mL PhysProp
logP 0.1 PhysProp
Predicted Properties
Property Value Source
water solubility 9.66e+01 g/l ALOGPS
logP -2.56 ALOGPS
logP -2.33 ChemAxon Molconvert
logS -0.13 ALOGPS
pKa ChemAxon Molconvert
hydrogen acceptor count 3 ChemAxon Molconvert
hydrogen donor count 2 ChemAxon Molconvert
polar surface area 63.32 ChemAxon Molconvert
rotatable bond count 4 ChemAxon Molconvert
refractivity 34.29 ChemAxon Molconvert
polarizability 13.64 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference
  1. Gram L, Larsson OM, Johnsen A, Schousboe A: Experimental studies of the influence of vigabatrin on the GABA system. Br J Clin Pharmacol. 1989;27 Suppl 1:13S-17S. Pubmed
  2. Browne TR: Pharmacokinetics of antiepileptic drugs. Neurology. 1998 Nov;51(5 Suppl 4):S2-7. Pubmed
  3. Lindberger M, Luhr O, Johannessen SI, Larsson S, Tomson T: Serum concentrations and effects of gabapentin and vigabatrin: observations from a dose titration study. Ther Drug Monit. 2003 Aug;25(4):457-62. Pubmed
  4. Zwanzger P, Baghai TC, Schuele C, Strohle A, Padberg F, Kathmann N, Schwarz M, Moller HJ, Rupprecht R: Vigabatrin decreases cholecystokinin-tetrapeptide (CCK-4) induced panic in healthy volunteers. Neuropsychopharmacology. 2001 Nov;25(5):699-703. Pubmed
External Links
Resource Link
KEGG Drug D00535 Link_out
KEGG Compound C07500 Link_out
PubChem Compound 5665 Link_out
PubChem Substance 46507052 Link_out
ChemSpider 5463 Link_out
BindingDB 50118886 Link_out
Therapeutic Targets Database DAP000557 Link_out
PharmGKB PA10231 Link_out
Drug Product Database 2068036 Link_out
Drugs.com http://www.drugs.com/cdi/vigabatrin.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Vigabatrin Link_out
ATC Codes
  • N03AG04
AHFS Codes
  • 28:12.92
PDB Entries
FDA label Not Available
MSDS Not Available
Interactions
Drug Interactions Not Available
Food Interactions Not Available
Targets

1. Gamma-aminobutyric acid type B receptor, subunit 1

Pharmacological action: yes
Actions: agonist

Isoform 1E function may be to regulate the availability of functional GABA-B-R1A/GABA-B-R2 heterodimers by competing for GABA-B-R2 dimerization. This could explain the observation that certain small molecule ligands exhibit differential affinity for central versus peripheral sites

Organism class: human
UniProt ID: Q9UBS5 Link_out
Gene: GABBR1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Tyacke RJ, Lingford-Hughes A, Reed LJ, Nutt DJ: GABAB receptors in addiction and its treatment. Adv Pharmacol. 2010;58:373-96. Pubmed

2. 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. Weber OM, Verhagen A, Duc CO, Meier D, Leenders KL, Boesiger P: Effects of vigabatrin intake on brain GABA activity as monitored by spectrally edited magnetic resonance spectroscopy and positron emission tomography. Magn Reson Imaging. 1999 Apr;17(3):417-25. Pubmed
  2. Valdizan EM, Garcia AP, Armijo JA: Effects of increasing doses of vigabatrin on platelet gamma-aminobutyric acid-transaminase and brain gamma-aminobutyric acid in rats. Eur J Pharmacol. 1999 Mar 19;369(2):169-73. Pubmed
  3. Arndt CF, Derambure P, Defoort-Dhellemmes S, Hache JC: Outer retinal dysfunction in patients treated with vigabatrin. Neurology. 1999 Apr 12;52(6):1201-5. Pubmed
  4. Molina PE, Ahmed N, Ajmal M, Dewey S, Volkow N, Fowler J, Abumrad N: Co-administration of gamma-vinyl GABA and cocaine: preclinical assessment of safety. Life Sci. 1999;65(11):1175-82. Pubmed
  5. French JA: Vigabatrin. Epilepsia. 1999;40 Suppl 5:S11-6. Pubmed
  6. 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 November 10, 2010 13:45

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.