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Vigabatrin

July 24, 2017
Common Name

Vigabatrin Description

Vigabatrin is only found in individuals that have used or taken this drug. It is 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)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. Structure

MOLSDF3D-SDFPDBSMILESInChI View 3D Structure

Synonyms

Value Source 4-amino-5-Hexenoic acidChEBI gamma-Vinyl gabaChEBI gamma-Vinyl-gamma-aminobutyric acidChEBI GVGChEBI VigabatrinaChEBI VigabatrineChEBI VigabatrinumChEBI 4-amino-5-HexenoateGenerator g-Vinyl gabaGenerator γ-vinyl gabaGenerator g-Vinyl-g-aminobutyrateGenerator g-Vinyl-g-aminobutyric acidGenerator gamma-Vinyl-gamma-aminobutyrateGenerator γ-vinyl-γ-aminobutyrateGenerator γ-vinyl-γ-aminobutyric acidGenerator Acid, gamma-vinyl-gamma-aminobutyricMeSH SabrilMeSH Yamanouchi brand OF vigabatrinMeSH gamma Vinyl gabaMeSH gamma-Vinyl-gabaMeSH SabrilexMeSH Vigabatrin aventis brandMeSH Hoechst brand OF vigabatrinMeSH Vigabatrin hoechst brandMeSH gamma Vinyl gamma aminobutyric acidMeSH Aventis brand OF vigabatrinMeSH Vigabatrin yamanouchi brandMeSH

Chemical Formlia

C6H11NO2 Average Molecliar Weight

129.157 Monoisotopic Molecliar Weight

129.078978601 IUPAC Name

4-aminohex-5-enoic acid Traditional Name

vigabatrin CAS Registry Number

60643-86-9 SMILES

NC(CCC(O)=O)C=C

InChI Identifier

InChI=1S/C6H11NO2/c1-2-5(7)3-4-6(8)9/h2,5H,1,3-4,7H2,(H,8,9)

InChI Key

PJDFLNIOAUIZSL-UHFFFAOYSA-N Chemical Taxonomy Description

This compound belongs to the class of chemical entities known as gamma amino acids and derivatives. These are amino acids having a (-NH2) group attached to the gamma carbon atom. Kingdom

Chemical entities Super Class

Organic compounds Class

Organic acids and derivatives Sub Class

Carboxylic acids and derivatives 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
  • Carbonyl compounds

    • Substituents

  • Gamma amino acid or derivatives
  • Medium-chain fatty acid
  • Amino fatty acid
  • Unsaturated fatty acid
  • Fatty acyl
  • Fatty acid
  • Amino acid
  • Carboxylic acid
  • Monocarboxylic acid or derivatives
  • Amine
  • Hydrocarbon derivative
  • Primary amine
  • Organooxygen compound
  • Organonitrogen compound
  • Organic oxide
  • Primary aliphatic amine
  • Organopnictogen compound
  • Organic oxygen compound
  • Carbonyl group
  • Organic nitrogen compound
  • Aliphatic acyclic compound

    • Molecliar Framework

    Aliphatic acyclic compounds External Descriptors

  • gamma-amino acid (CHEBI:63638 )

    • Ontology Status

    Expected but not Quantified Origin

  • Drug

    • Biofunction

  • Anticonvlisants
  • Enzyme Inhibitors
  • GABA Agents

    • Application

  • Pharmaceutical

    • Cellliar locations

  • Cytoplasm
  • Extracellliar
  • Membrane

    • Physical Properties State

    Solid Experimental Properties

    Property Value Reference Melting PointNot AvailableNot Available Boiling PointNot AvailableNot Available Water Solubility9.66e+01 g/LNot Available LogP0.1Not Available

    Predicted Properties

    Property Value Source 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 Rlie of FiveYesChemAxon Ghose FilterYesChemAxon Vebers RlieYesChemAxon MDDR-like RlieYesChemAxon

    Spectra Spectra

    Spectrum Type Description Splash Key LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-QFT , positivesplash10-00di-9400000000-0215823a9ba364cc48cbView in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-QFT , positivesplash10-00di-9400000000-c7d21d36dfb8e7079ee2View in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-QFT , positivesplash10-00di-9200000000-e0c504f980ef5bbc0501View in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-QFT , positivesplash10-00di-9000000000-e1b2ea8d5a2da84a5a64View in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-QFT , positivesplash10-00di-9000000000-52958176067fd9bae916View in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-QFT , positivesplash10-00di-9000000000-263da4b132ca66986967View in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-QFT , positivesplash10-01b9-9000000000-1f8826cc32ef269c1a7cView in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-QFT , positivesplash10-014i-9000000000-32306e2f90cd529accc7View in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-QFT , positivesplash10-0gb9-9000000000-aefa9f2682087c7b78edView in MoNA Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 10V, PositiveNot Available Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 20V, PositiveNot Available Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 40V, PositiveNot Available Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 10V, NegativeNot Available Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 20V, NegativeNot Available Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 40V, NegativeNot Available

    Biological Properties Cellliar Locations

  • Cytoplasm
  • Extracellliar
  • Membrane

    • Biofluid Locations

  • Blood
  • Urine

    • Tissue Location

    Not Available Pathways

    Not Available Normal Concentrations

    Biofluid Status Value Age Sex Condition Reference Details BloodExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB01080

  • 21059682

    • details UrineExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB01080

  • 21059682

    • details

    Abnormal Concentrations

    Not Available Predicted Concentrations

    Biofluid Value Original age Original sex Original condition Comments Blood0-8 uMAdlit (>18 years old)BothNormalPredicted based on drug qualities Blood0-4 umol/mmol creatinineAdlit (>18 years old)BothNormalPredicted based on drug qualities

    Associated Disorders and Diseases Disease References

    None Associated OMIM IDs

    None External Links DrugBank ID

    DB01080 DrugBank Metabolite ID

    Not Available Phenol Explorer Compound ID

    Not Available Phenol Explorer Metabolite ID

    Not Available FoodDB ID

    Not Available KNApSAcK ID

    Not Available Chemspider ID

    5463 KEGG Compound ID

    C07500 BioCyc ID

    Not Available BiGG ID

    Not Available Wikipedia Link

    Vigabatrin NuGOwiki Link

    HMDB15212 Metagene Link

    HMDB15212 METLIN ID

    Not Available PubChem Compound

    5665 PDB ID

    Not Available ChEBI ID

    63638

    Product: MMAF (Hydrochloride)

    References Synthesis Reference Not Available Material Safety Data Sheet (MSDS) Not Available General References
    1. 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:12883229 ]
    2. 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 ]
    3. Browne TR: Pharmacokinetics of antiepileptic drugs. Neurology. 1998 Nov;51(5 Suppl 4):S2-7. [PubMed:9818917 ]
    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:11682253 ]
    5. Hawker DD, Silverman RB: Synthesis and evaluation of novel heteroaromatic substrates of GABA aminotransferase. Bioorg Med Chem. 2012 Oct 1;20(19):5763-73. doi: 10.1016/j.bmc.2012.08.009. Epub 2012 Aug 16. [PubMed:22944334 ]
    6. 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 ]
    7. Clayton LM, Stern WM, Newman WD, Sander JW, Acheson J, Sisodiya SM: Evolution of visual field loss over ten years in individuals taking vigabatrin. Epilepsy Res. 2013 Aug;105(3):262-71. doi: 10.1016/j.eplepsyres.2013.02.014. Epub 2013 Mar 28. [PubMed:23541931 ]

    Enzymes

    General function:
    Involved in 4-aminobutyrate transaminase activity
    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.
    Gene Name:
    ABAT
    Uniprot ID:
    P80404
    Molecular weight:
    56438.405
    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. 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:10214744 ]
    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:10503933 ]
    5. French JA: Vigabatrin. Epilepsia. 1999;40 Suppl 5:S11-6. [PubMed:10530689 ]
    6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
    General function:
    Involved in G-protein coupled receptor activity
    Specific function:
    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
    Gene Name:
    GABBR1
    Uniprot ID:
    Q9UBS5
    Molecular weight:
    108319.4
    References
    1. Tyacke RJ, Lingford-Hughes A, Reed LJ, Nutt DJ: GABAB receptors in addiction and its treatment. Adv Pharmacol. 2010;58:373-96. doi: 10.1016/S1054-3589(10)58014-1. [PubMed:20655489 ]

    PMID: 27600527

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