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Tetrabenazine

July 24, 2017
Common Name

Tetrabenazine Description

A drug formerly used as an antipsychotic but now used primarily in the treatment of various movement disorders including tardive dyskinesia. Tetrabenazine blocks uptake into adrenergic storage vesicles and has been used as a high affinity label for the vesicle transport system. [PubChem] Structure

MOLSDF3D-SDFPDBSMILESInChI View 3D Structure

Synonyms

Value Source 1,2,4,6,7,11b-hexahydro-3-Isobutyl-9,10-dimethoxy-2H-benzo[a]quinolizin-2-oneChEBI 2-oxo-3-Isobutyl-9,10-dimethoxy-1,2,3,4,6,7-hexahydro-11BH-benzo[a]quinolizineChEBI 2-oxo-3-Isobutyl-9,10-dimethoxy-1,3,4,6,7,11b-hexahydro-2H-benzoquinolizineChEBI ro 1-9569HMDB TBZHMDB Tetra benazinHMDB TetrabenzaineHMDB TetrabenzineHMDB Tetrabenazine orphan brandMeSH Cambridge laboratories brand OF tetrabenazineMeSH Orphan brand OF tetrabenazineMeSH Roche brand OF tetrabenazineMeSH Shire brand OF tetrabenazineMeSH XenazineMeSH NitomanMeSH

Chemical Formlia

C19H27NO3 Average Molecliar Weight

317.4226 Monoisotopic Molecliar Weight

317.199093735 IUPAC Name

9,10-dimethoxy-3-(2-methylpropyl)-1H,2H,3H,4H,6H,7H,11bH-pyrido[2,1-a]isoquinolin-2-one Traditional Name

tetrabenazine CAS Registry Number

58-46-8 SMILES

COC1=C(OC)C=C2C3CC(=O)C(CC(C)C)CN3CCC2=C1

InChI Identifier

InChI=1S/C19H27NO3/c1-12(2)7-14-11-20-6-5-13-8-18(22-3)19(23-4)9-15(13)16(20)10-17(14)21/h8-9,12,14,16H,5-7,10-11H2,1-4H3

InChI Key

MKJIEFSOBYUXJB-UHFFFAOYSA-N Chemical Taxonomy Description

This compound belongs to the class of chemical entities known as tetrahydroisoquinolines. These are tetrahydrogenated isoquinoline derivatives. Kingdom

Chemical entities Super Class

Organic compounds Class

Organoheterocyclic compounds Sub Class

Tetrahydroisoquinolines Direct Parent

Tetrahydroisoquinolines Alternative Parents

  • Anisoles
  • Piperidinones
  • Aralkylamines
  • Alkyl aryl ethers
  • Trialkylamines
  • Cyclic ketones
  • Azacyclic compounds
  • Organopnictogen compounds
  • Organic oxides
  • Hydrocarbon derivatives

    • Substituents

  • Tetrahydroisoquinoline
  • Anisole
  • Alkyl aryl ether
  • Piperidinone
  • Aralkylamine
  • Piperidine
  • Benzenoid
  • Ketone
  • Tertiary amine
  • Tertiary aliphatic amine
  • Cyclic ketone
  • Ether
  • Azacycle
  • Amine
  • Organic oxide
  • Organopnictogen compound
  • Organooxygen compound
  • Organonitrogen compound
  • Organic nitrogen compound
  • Carbonyl group
  • Hydrocarbon derivative
  • Organic oxygen compound
  • Aromatic heteropolycyclic compound

    • Molecliar Framework

    Aromatic heteropolycyclic compounds External Descriptors

  • cyclic ketone (CHEBI:64028 )
  • tertiary amino compound (CHEBI:64028 )
  • benzoquinolizine (CHEBI:64028 )

    • Ontology Status

    Expected but not Quantified Origin

  • Drug

    • Biofunction

  • Adrenergic Uptake Inhibitors

    • Application

  • Pharmaceutical

    • Cellliar locations

  • Cytoplasm
  • Membrane

    • Physical Properties State

    Solid Experimental Properties

    Property Value Reference Melting Point128 °CNot Available Boiling PointNot AvailableNot Available Water Solubility3.61e-01 g/LNot Available LogPNot AvailableNot Available

    Predicted Properties

    Property Value Source Water Solubility0.36 mg/mLALOGPS logP3.23ALOGPS logP3.4ChemAxon logS-2.9ALOGPS pKa (Strongest Acidic)18.24ChemAxon pKa (Strongest Basic)7.41ChemAxon Physiological Charge1ChemAxon Hydrogen Acceptor Count4ChemAxon Hydrogen Donor Count0ChemAxon Polar Surface Area38.77 Å2ChemAxon Rotatable Bond Count4ChemAxon Refractivity91.31 m3·mol-1ChemAxon Polarizability36.59 Å3ChemAxon Number of Rings3ChemAxon Bioavailability1ChemAxon Rlie of FiveYesChemAxon Ghose FilterYesChemAxon Vebers RlieYesChemAxon MDDR-like RlieYesChemAxon

    Spectra Spectra

    Spectrum Type Description Splash Key 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
  • 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 DB04844

  • 21059682

    • details UrineExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB04844

  • 21059682

    • details

    Abnormal Concentrations

    Not Available Associated Disorders and Diseases Disease References

    None Associated OMIM IDs

    None External Links DrugBank ID

    DB04844 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

    5796 KEGG Compound ID

    C11168 BioCyc ID

    Not Available BiGG ID

    Not Available Wikipedia Link

    Tetrabenazine NuGOwiki Link

    HMDB15592 Metagene Link

    HMDB15592 METLIN ID

    Not Available PubChem Compound

    6018 PDB ID

    Not Available ChEBI ID

    64028

    Product: Pentamidine

    References Synthesis Reference Not Available Material Safety Data Sheet (MSDS) Not Available General References
    1. Jankovic J, Beach J: Long-term effects of tetrabenazine in hyperkinetic movement disorders. Neurology. 1997 Feb;48(2):358-62. [PubMed:9040721 ]
    2. Guay DR: Tetrabenazine, a monoamine-depleting drug used in the treatment of hyperkinetic movement disorders. Am J Geriatr Pharmacother. 2010 Aug;8(4):331-73. doi: 10.1016/j.amjopharm.2010.08.006. [PubMed:20869622 ]

    Enzymes

    General function:
    Involved in monooxygenase activity
    Specific function:
    Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants.
    Gene Name:
    CYP2D6
    Uniprot ID:
    P10635
    Molecular weight:
    55768.94
    References
    1. Poon LH, Kang GA, Lee AJ: Role of tetrabenazine for Huntingtons disease-associated chorea. Ann Pharmacother. 2010 Jun;44(6):1080-9. doi: 10.1345/aph.1M582. Epub 2010 May 4. [PubMed:20442355 ]
    General function:
    Involved in transmembrane transport
    Specific function:
    Involved in the ATP-dependent vesicular transport of biogenic amine neurotransmitters. Pumps cytosolic monoamines including dopamine, norepinephrine, serotonin, and histamine into synaptic vesicles. Requisite for vesicular amine storage prior to secretion via exocytosis
    Gene Name:
    SLC18A2
    Uniprot ID:
    Q05940
    Molecular weight:
    55712.1
    References
    1. Zheng G, Dwoskin LP, Crooks PA: Vesicular monoamine transporter 2: role as a novel target for drug development. AAPS J. 2006 Nov 10;8(4):E682-92. [PubMed:17233532 ]
    2. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
    3. Kim YS, Shin JH, Hall FS, Linden DJ: Dopamine signaling is required for depolarization-induced slow current in cerebellar Purkinje cells. J Neurosci. 2009 Jul 1;29(26):8530-8. doi: 10.1523/JNEUROSCI.0468-09.2009. [PubMed:19571144 ]
    4. Goland R, Freeby M, Parsey R, Saisho Y, Kumar D, Simpson N, Hirsch J, Prince M, Maffei A, Mann JJ, Butler PC, Van Heertum R, Leibel RL, Ichise M, Harris PE: 11C-dihydrotetrabenazine PET of the pancreas in subjects with long-standing type 1 diabetes and in healthy controls. J Nucl Med. 2009 Mar;50(3):382-9. doi: 10.2967/jnumed.108.054866. Epub 2009 Feb 17. [PubMed:19223416 ]
    5. Gros Y, Schuldiner S: Directed evolution reveals hidden properties of VMAT, a neurotransmitter transporter. J Biol Chem. 2010 Feb 12;285(7):5076-84. doi: 10.1074/jbc.M109.081216. Epub 2009 Dec 10. [PubMed:20007701 ]
    6. Wimalasena K: Vesicular monoamine transporters: structure-function, pharmacology, and medicinal chemistry. Med Res Rev. 2011 Jul;31(4):483-519. doi: 10.1002/med.20187. Epub 2010 Feb 4. [PubMed:20135628 ]

    PMID: 26771351

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