Identification

Name
Vigabatrin
Accession Number
DB01080
Description

Vigabatrin is an analog of gamma-aminobutyric acid (GABA), the main inhibitory neurotransmitter in the central nervous system, used in the treatment of refractory seizures and infantile spasms.7 It irreversibly inhibits the enzyme responsible for GABA metabolism, thereby increasing levels of circulating GABA. Although administered as a racemic mixture, only the S(+) enantiomer is pharmacologically active.4

It was first introduced as an antiepileptic agent in the United Kingdom in 1989 and was used extensively until 1997, when an association with vision loss became apparent.6 Its use is now generally reserved for patients who have failed alternative therapies, and its US approval by the FDA in 2009 mandated the creation of a drug registry to monitor patients for visual deficits.9,6

Type
Small Molecule
Groups
Approved
Structure
Thumb
Weight
Average: 129.157
Monoisotopic: 129.078978601
Chemical Formula
C6H11NO2
Synonyms
  • 4-Amino-5-hexenoic acid
  • Gamma vinyl GABA
  • gamma-Vinyl GABA
  • gamma-Vinyl-gamma-aminobutyric acid
  • GVG
  • Vigabatrin
  • Vigabatrina
  • Vigabatrine
  • Vigabatrinum
  • Vinyl gamma-aminobutyric acid
External IDs
  • CPP-109
  • MDL 71,754
  • MDL-71754
  • RMI-71754

Pharmacology

Indication

Vigabatrin is indicated as adjunctive therapy in the treatment of refractory complex partial seizures in patients 2 years of age and older who have had inadequate responses to multiple previous treatments (i.e. not to be used for first-line therapy).7 It is also indicated as monotherapy in the treatment of infantile spasms in patients between 1 month and 2 years of age for whom the potential benefits outweigh the risk of vision loss.7

Associated Conditions
Contraindications & Blackbox Warnings
Learn about our commercial Contraindications & Blackbox Warnings data.
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Pharmacodynamics

Vigabatrin is an antiepileptic agent chemically unrelated to other anticonvulsants. Vigabatrin prevents the metabolism of GABA by irreversibly inhibiting GABA transaminase (GABA-T). As vigabatrin is an irreversible inhibitor of gamma-aminobutyric acid transaminase (GABA-T), its duration of effect is thought to be dependent on the rate of GABA-T re-synthesis rather than on the rate of drug elimination.7

Mechanism of action

Gamma-aminobutyric acid (GABA) is the major inhibitory transmitter throughout the central nervous system, and the potentiation of GABAergic neurotransmission is therefore a crucial mechanism through which antiepileptic agents may combat the pathologic excitatory neurotransmission seen in epilepsy.5 Vigabatrin increases concentrations of GABA in the central nervous system by irreversibly inhibiting the enzymes responsible for its metabolism to succinic semialdehyde: gamma-aminobutyric acid transaminase (GABA-T).7

TargetActionsOrganism
A4-aminobutyrate aminotransferase, mitochondrial
inhibitor
Humans
Absorption

Absorption following oral administration is essentially complete.7 The Tmax is approximately 2.5 hours in infants (5m - 2y) and 1 hour in all other age groups.

Volume of distribution

Vigabatrin is widely distributed throughout the body with a mean steady-state volume of distribution of 1.1 L/kg.7

Protein binding

Vigabatrin does not bind to plasma proteins.7

Metabolism

Vigabatrin is not metabolized to any significant extent.7

Route of elimination

Approximately 95% of the drug is eliminated in the urine within 72 hours of administration, of which ~80% is unchanged parent drug.7

Half-life

The terminal half-life of vigabatrin is approximately 5.7 hours for infants (5m - 2y), 6.8 hours for children (3y - 9y), 9.5 hours for adolescents (10y - 16y), and 10.5 h for adults.7

Clearance

The oral clearance of vigabatrin is 2.4 L/h for infants (5m - 2y), 5.1 L/h for children (3y - 9y), 5.8 L/h for adolescents (10y - 16y), and 7 L/h for adults.7

Adverse Effects
Learn about our commercial Adverse Effects data.
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Toxicity

The oral LD50 of vigabatrin in mice and rats is 2830 mg/kg and 3100 mg/kg, respectively.8 Symptoms of overdose tend to involve significant CNS depression - e.g. coma, unconsciousness, and/or drowsiness - with less common symptoms including neurologic disorders (e.g. seizure activity, speech disorder, headache) and psychiatric sequelae (e.g. psychosis, agitation, abnormal behaviour, confusion).7

In cases of overdose, symptoms generally resolve with symptomatic and supportive care. Standard measures to remove unabsorbed drug may be employed (e.g. gastric lavage), although an in vitro study found that activated charcoal did not significantly absorb vigabatrin.7 Although vigabatrin is not protein-bound, the effectiveness of hemodialysis in drug removal during overdose is unknown - isolated reports of patients in renal failure undergoing hemodialysis who were receiving therapeutic doses of vigabatrin note a reduction in vigabatrin plasma concentrations of 40-60% following dialysis.7

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AcetazolamideThe risk or severity of adverse effects can be increased when Acetazolamide is combined with Vigabatrin.
AcetophenazineThe risk or severity of adverse effects can be increased when Acetophenazine is combined with Vigabatrin.
AclidiniumVigabatrin may increase the central nervous system depressant (CNS depressant) activities of Aclidinium.
AgomelatineThe risk or severity of adverse effects can be increased when Vigabatrin is combined with Agomelatine.
AlfentanilThe risk or severity of adverse effects can be increased when Alfentanil is combined with Vigabatrin.
AlimemazineThe risk or severity of adverse effects can be increased when Vigabatrin is combined with Alimemazine.
AlmotriptanThe risk or severity of adverse effects can be increased when Almotriptan is combined with Vigabatrin.
AlosetronThe risk or severity of adverse effects can be increased when Alosetron is combined with Vigabatrin.
AlprazolamThe risk or severity of adverse effects can be increased when Alprazolam is combined with Vigabatrin.
AlverineThe risk or severity of adverse effects can be increased when Vigabatrin is combined with Alverine.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

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  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level

    A rating for the strength of the evidence supporting each drug interaction.

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  • Action
    Action

    An effect category for each drug interaction. Know how this interaction affects the subject drug.

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Food Interactions
  • Take with or without food.
  • Take with plain water. Only mix vigabatrin oral solution powder with plain water.

Products

International/Other Brands
Sabrilan (Lundbeck Inc. ) / Sabrilex (Lundbeck Inc. )
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
SabrilPowder, for solution500 mgOralLundbeck Pharmaceuticals Llc1997-08-20Not applicableCanada flag
SabrilPowder, for solution50 mg/1mLOralLundbeck Pharmaceuticals Llc2009-08-21Not applicableUS flag
SabrilTablet500 mgOralLundbeck Pharmaceuticals Llc1994-12-31Not applicableCanada flag
SabrilTablet, film coated500 mg/1OralLundbeck Pharmaceuticals Llc2009-08-21Not applicableUS flag
Sabril Pwr 1g/sachetPowderOralAventis Pharma Ltd.Not applicableNot applicableCanada flag
Sabril Pwr 2g/sachetPowderOralAventis Pharma Ltd.Not applicableNot applicableCanada flag
Sabril Pwr 3g/sachetPowderOralAventis Pharma Ltd.Not applicableNot applicableCanada flag
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
VigabatrinPowder, for solution50 mg/1mLOralDr. Reddy’s Laboratories Inc.,2018-11-21Not applicableUS flag
VigabatrinPowder, for solution500 mg/1mLOralCipla USA, Inc.2019-12-04Not applicableUS flag
VigabatrinTablet, film coated500 mg/1OralActavis Pharma, Inc.2019-02-06Not applicableUS flag
VigabatrinFor solution500 mg/1OralAmneal Pharmaceuticals NY LLC2018-03-19Not applicableUS flag
VigabatrinPowder, for solution50 mg/1mLOralActavis Pharma, Inc.2020-05-14Not applicableUS flag
VigabatrinPowder, for solution50 mg/1mLOralPar Pharmaceutical, Inc.2017-04-27Not applicableUS flag
Vigabatrin for oral solution USP, 500 mgFor solution50 mg/1mLOralHikma Pharmaceuticals USA Inc.2020-07-10Not applicableUS flag
VigadronePowder, for solution50 mg/1mLOralUpsher-Smith Laboratories, LLC2018-06-21Not applicableUS flag
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

    Learn more
  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Categories

ATC Codes
N03AG04 — Vigabatrin
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as gamma amino acids and derivatives. These are amino acids having a (-NH2) group attached to the gamma carbon atom.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Carboxylic acids and derivatives
Sub Class
Amino acids, peptides, and analogues
Direct Parent
Gamma amino acids and derivatives
Alternative Parents
Medium-chain fatty acids / Amino fatty acids / Unsaturated fatty acids / Amino acids / Monocarboxylic acids and derivatives / Carboxylic acids / Organopnictogen compounds / Organic oxides / Monoalkylamines / Hydrocarbon derivatives
show 1 more
Substituents
Aliphatic acyclic compound / Amine / Amino acid / Amino fatty acid / Carbonyl group / Carboxylic acid / Fatty acid / Fatty acyl / Gamma amino acid or derivatives / Hydrocarbon derivative
show 11 more
Molecular Framework
Aliphatic acyclic compounds
External Descriptors
gamma-amino acid (CHEBI:63638)

Chemical Identifiers

UNII
GR120KRT6K
CAS number
68506-86-5
InChI Key
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)
IUPAC Name
4-aminohex-5-enoic acid
SMILES
NC(CCC(O)=O)C=C

References

General References
  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:2757904]
  2. 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:11682253]
  3. Tulloch JK, Carr RR, Ensom MH: A systematic review of the pharmacokinetics of antiepileptic drugs in neonates with refractory seizures. J Pediatr Pharmacol Ther. 2012 Jan;17(1):31-44. doi: 10.5863/1551-6776-17.1.31. [PubMed:23118657]
  4. Jacqz-Aigrain E, Guillonneau M, Rey E, Macher MA, Montes C, Chiron C, Loirat C: Pharmacokinetics of the S(+) and R(-) enantiomers of vigabatrin during chronic dosing in a patient with renal failure. Br J Clin Pharmacol. 1997 Aug;44(2):183-5. doi: 10.1046/j.1365-2125.1997.00636.x. [PubMed:9278207]
  5. Davies JA: Mechanisms of action of antiepileptic drugs. Seizure. 1995 Dec;4(4):267-71. doi: 10.1016/s1059-1311(95)80003-4. [PubMed:8719918]
  6. Foroozan R: Vigabatrin: Lessons Learned From the United States Experience. J Neuroophthalmol. 2018 Dec;38(4):442-450. doi: 10.1097/WNO.0000000000000609. [PubMed:29280765]
  7. FDA Approved Drug Products: Sabril (vigabatrin) for oral use [Link]
  8. Health Canada Product Monograph: Sabril (vigabatrin) for oral use [Link]
  9. Vigabatrin REMS Program [Link]
Human Metabolome Database
HMDB0015212
KEGG Drug
D00535
KEGG Compound
C07500
PubChem Compound
5665
PubChem Substance
46507052
ChemSpider
5463
BindingDB
50118886
RxNav
14851
ChEBI
63638
ChEMBL
CHEMBL89598
Therapeutic Targets Database
DAP000557
PharmGKB
PA10231
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Vigabatrin
AHFS Codes
  • 28:12.92 — Miscellaneous Anticonvulsants
MSDS
Download (63.9 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedSupportive CareAdult Refractory Complex Partial Seizures1
4RecruitingTreatmentEpilepsies1
4TerminatedTreatmentComplex Partial Seizures1
4WithdrawnNot AvailableInfantile Spasms (IS)1
3Active Not RecruitingTreatmentInfantile Spasms (IS)1
3SuspendedTreatmentCosyntropin / Infantile Spasms (IS) / Vigabatrin1
3WithdrawnTreatmentInfantile Spasms (IS)1
2Active Not RecruitingPreventionTuberous Sclerosis Complex (TSC)1
2CompletedTreatmentDependence, Cocaine2
2Not Yet RecruitingOtherBMI >30 kg/m2 / NAFLD1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Lundbeck Inc.
Dosage Forms
FormRouteStrength
Tablet, solubleOral100 MG
Tablet, solubleOral500 MG
Granule, for solutionOral1 G
Granule, for solutionOral500 MG
Powder, for solutionOral50 mg/1mL
Powder, for solutionOral500 mg
Tablet, coatedOral500 MG
Tablet, film coatedOral500 mg/1
Tablet500 mg
TabletOral500 mg
Tablet
PowderOral
For solutionOral500 mg/1
Powder, for solutionOral500 mg/1mL
For solutionOral50 mg/1mL
Prices
Unit descriptionCostUnit
Sabril 500 mg tablet16.66USD tablet
Sabril 500 mg Powder Packet0.95USD packet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)171-176CFDA Label
water solubility55.1 mg/mLFDA Label
logP-1.96FDA Label
pKa4 and 9.7FDA Label
Predicted Properties
PropertyValueSource
Water Solubility96.6 mg/mLALOGPS
logP-2.6ALOGPS
logP-2.1ChemAxon
logS-0.13ALOGPS
pKa (Strongest Acidic)4.61ChemAxon
pKa (Strongest Basic)9.91ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area63.32 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity34.29 m3·mol-1ChemAxon
Polarizability13.64 Å3ChemAxon
Number of Rings0ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.9213
Blood Brain Barrier+0.9382
Caco-2 permeable-0.5191
P-glycoprotein substrateNon-substrate0.797
P-glycoprotein inhibitor INon-inhibitor0.949
P-glycoprotein inhibitor IINon-inhibitor0.9856
Renal organic cation transporterNon-inhibitor0.8944
CYP450 2C9 substrateNon-substrate0.8785
CYP450 2D6 substrateNon-substrate0.8115
CYP450 3A4 substrateNon-substrate0.7664
CYP450 1A2 substrateNon-inhibitor0.9149
CYP450 2C9 inhibitorNon-inhibitor0.9389
CYP450 2D6 inhibitorNon-inhibitor0.9654
CYP450 2C19 inhibitorNon-inhibitor0.963
CYP450 3A4 inhibitorNon-inhibitor0.8309
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9824
Ames testNon AMES toxic0.8409
CarcinogenicityNon-carcinogens0.7678
BiodegradationReady biodegradable0.7494
Rat acute toxicity1.6656 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9617
hERG inhibition (predictor II)Non-inhibitor0.9772
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-00di-9400000000-0215823a9ba364cc48cb
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-00di-9400000000-c7d21d36dfb8e7079ee2
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-00di-9200000000-e0c504f980ef5bbc0501
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-00di-9000000000-e1b2ea8d5a2da84a5a64
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-00di-9000000000-52958176067fd9bae916
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-00di-9000000000-263da4b132ca66986967
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-01b9-9000000000-1f8826cc32ef269c1a7c
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-014i-9000000000-32306e2f90cd529accc7
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0gb9-9000000000-aefa9f2682087c7b78ed

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Succinate-semialdehyde dehydrogenase binding
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-al...
Gene Name
ABAT
Uniprot ID
P80404
Uniprot Name
4-aminobutyrate aminotransferase, mitochondrial
Molecular Weight
56438.405 Da
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:10195585]
  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:10206175]
  3. FDA Approved Drug Products: Sabril (vigabatrin) for oral use [Link]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inducer
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. FDA Approved Drug Products: Sabril (vigabatrin) for oral use [Link]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
L-proline transmembrane transporter activity
Specific Function
Neutral amino acid/proton symporter. Has a pH-dependent electrogenic transport activity for small amino acids such as glycine, alanine and proline. Besides small apolar L-amino acids, it also recog...
Gene Name
SLC36A1
Uniprot ID
Q7Z2H8
Uniprot Name
Proton-coupled amino acid transporter 1
Molecular Weight
53075.045 Da
References
  1. Abbot EL, Grenade DS, Kennedy DJ, Gatfield KM, Thwaites DT: Vigabatrin transport across the human intestinal epithelial (Caco-2) brush-border membrane is via the H+ -coupled amino-acid transporter hPAT1. Br J Pharmacol. 2006 Feb;147(3):298-306. [PubMed:16331283]

Drug created on June 13, 2005 07:24 / Updated on September 17, 2020 23:28

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