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Tofisopam

July 24, 2017
Common Name

Tofisopam Description

Tofisopam (marketed under brand names Emandaxin and Grandaxin) is a 2,3-benzodiazepine drug which is a benzodiazepine derivative. In contrast to classical 1,4-benzodiazepines, the compound does not bind to the benzodiazepine binding site of the gamma-aminobutyric acid receptor and its psychopharmacological profile differs from such compounds. Although Tofisopam is not approved for sale in North America, it is approved for use in various countries worldwide, including parts of Europe. The D-enantiomer (dextofisopam) is currently in phase II trials in the U.S. for the treatment of irritable bowel syndrome. Structure

MOLSDF3D-SDFPDBSMILESInChI View 3D Structure

Synonyms

Value Source EmandaxinKegg TofizopamHMDB EGYT-341MeSH LevotofisopamMeSH DextofisopamMeSH GrandaxinMeSH 1-(3,4-Dimethoxyphenyl)-5-ethyl-7,8-dimethoxy-4-methyl-5H-2,3-benzodiazepineMeSH

Chemical Formlia

C22H26N2O4 Average Molecliar Weight

382.4528 Monoisotopic Molecliar Weight

382.18925733 IUPAC Name

1-(3,4-dimethoxyphenyl)-5-ethyl-7,8-dimethoxy-4-methyl-5H-2,3-benzodiazepine Traditional Name

seriel CAS Registry Number

22345-47-7 SMILES

CCC1C2=CC(OC)=C(OC)C=C2C(=NN=C1C)C1=CC(OC)=C(OC)C=C1

InChI Identifier

InChI=1S/C22H26N2O4/c1-7-15-13(2)23-24-22(14-8-9-18(25-3)19(10-14)26-4)17-12-21(28-6)20(27-5)11-16(15)17/h8-12,15H,7H2,1-6H3

InChI Key

RUJBDQSFYCKFAA-UHFFFAOYSA-N Chemical Taxonomy Description

This compound belongs to the class of chemical entities known as benzodiazepines. These are organic compounds containing a benzene ring fused to either isomers of diazepine(unsaturated seven-member heterocycle with two nitrogen atoms replacing two carbon atoms). Kingdom

Chemical entities Super Class

Organic compounds Class

Organoheterocyclic compounds Sub Class

Benzodiazepines Direct Parent

Benzodiazepines Alternative Parents

  • Dimethoxybenzenes
  • Phenoxy compounds
  • Anisoles
  • Alkyl aryl ethers
  • Azacyclic compounds
  • Organopnictogen compounds
  • Organonitrogen compounds
  • Hydrocarbon derivatives

    • Substituents

  • Benzodiazepine
  • Dimethoxybenzene
  • O-dimethoxybenzene
  • Phenoxy compound
  • Anisole
  • Phenol ether
  • Methoxybenzene
  • Alkyl aryl ether
  • Monocyclic benzene moiety
  • Benzenoid
  • Ether
  • Azacycle
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Organopnictogen compound
  • Organic nitrogen compound
  • Organic oxygen compound
  • Aromatic heteropolycyclic compound

    • Molecliar Framework

    Aromatic heteropolycyclic compounds External Descriptors

    Not Available Ontology Status

    Expected but not Quantified Origin

  • Drug

    • Biofunction

  • Benzodiazepines

    • Application

  • Pharmaceutical

    • Cellliar locations

  • Membrane

    • Physical Properties State

    Solid Experimental Properties

    Property Value Reference Melting Point152 °CNot Available Boiling PointNot AvailableNot Available Water SolubilityNot AvailableNot Available LogPNot AvailableNot Available

    Predicted Properties

    Property Value Source Water Solubility0.0024 mg/mLALOGPS logP4.29ALOGPS logP3.83ChemAxon logS-5.2ALOGPS pKa (Strongest Basic)-2.2ChemAxon Physiological Charge0ChemAxon Hydrogen Acceptor Count6ChemAxon Hydrogen Donor Count0ChemAxon Polar Surface Area61.64 Å2ChemAxon Rotatable Bond Count6ChemAxon Refractivity109.03 m3·mol-1ChemAxon Polarizability42.14 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

  • 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 DB08811

  • 21059682

    • details UrineExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB08811

  • 21059682

    • details

    Abnormal Concentrations

    Not Available Predicted Concentrations

    Biofluid Value Original age Original sex Original condition Comments Blood0-0.3 uMAdlit (>18 years old)BothNormalPredicted based on drug qualities Blood0-0.1 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

    DB08811 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

    5301 KEGG Compound ID

    Not Available BioCyc ID

    Not Available BiGG ID

    Not Available Wikipedia Link

    Tofisopam NuGOwiki Link

    HMDB15699 Metagene Link

    HMDB15699 METLIN ID

    Not Available PubChem Compound

    5502 PDB ID

    Not Available ChEBI ID

    518452

    Product: Spironolactone

    References Synthesis Reference Not Available Material Safety Data Sheet (MSDS) Not Available General References
    1. Rundfeldt C, Socala K, Wlaz P: The atypical anxiolytic drug, tofisopam, selectively blocks phosphodiesterase isoenzymes and is active in the mouse model of negative symptoms of psychosis. J Neural Transm (Vienna). 2010 Nov;117(11):1319-25. doi: 10.1007/s00702-010-0507-3. Epub 2010 Oct 22. [PubMed:20967473 ]

    Enzymes

    General function:
    Involved in catalytic activity
    Specific function:
    Cyclic nucleotide phosphodiesterase with a dual-specificity for the second messengers cAMP and cGMP, which are key regulators of many important physiological processes (By similarity).
    Gene Name:
    PDE3A
    Uniprot ID:
    Q14432
    Molecular weight:
    124978.06
    References
    1. Rundfeldt C, Socala K, Wlaz P: The atypical anxiolytic drug, tofisopam, selectively blocks phosphodiesterase isoenzymes and is active in the mouse model of negative symptoms of psychosis. J Neural Transm (Vienna). 2010 Nov;117(11):1319-25. doi: 10.1007/s00702-010-0507-3. Epub 2010 Oct 22. [PubMed:20967473 ]
    General function:
    Involved in catalytic activity
    Specific function:
    Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides. Can hydrolyze both cAMP and cGMP, but has higher affinity for cAMP and is more efficient with cAMP as substrate.
    Gene Name:
    PDE10A
    Uniprot ID:
    Q9Y233
    Molecular weight:
    89388.7
    References
    1. Rundfeldt C, Socala K, Wlaz P: The atypical anxiolytic drug, tofisopam, selectively blocks phosphodiesterase isoenzymes and is active in the mouse model of negative symptoms of psychosis. J Neural Transm (Vienna). 2010 Nov;117(11):1319-25. doi: 10.1007/s00702-010-0507-3. Epub 2010 Oct 22. [PubMed:20967473 ]
    General function:
    Involved in catalytic activity
    Specific function:
    Cyclic nucleotide phosphodiesterase with a dual-specificity for the second messengers cAMP and cGMP, which are key regulators of many important physiological processes.
    Gene Name:
    PDE2A
    Uniprot ID:
    O00408
    Molecular weight:
    105145.485
    References
    1. Rundfeldt C, Socala K, Wlaz P: The atypical anxiolytic drug, tofisopam, selectively blocks phosphodiesterase isoenzymes and is active in the mouse model of negative symptoms of psychosis. J Neural Transm (Vienna). 2010 Nov;117(11):1319-25. doi: 10.1007/s00702-010-0507-3. Epub 2010 Oct 22. [PubMed:20967473 ]
    General function:
    Involved in 3,5-cyclic-nucleotide phosphodiesterase activity
    Specific function:
    Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes.
    Gene Name:
    PDE4A
    Uniprot ID:
    P27815
    Molecular weight:
    98142.155
    References
    1. Rundfeldt C, Socala K, Wlaz P: The atypical anxiolytic drug, tofisopam, selectively blocks phosphodiesterase isoenzymes and is active in the mouse model of negative symptoms of psychosis. J Neural Transm (Vienna). 2010 Nov;117(11):1319-25. doi: 10.1007/s00702-010-0507-3. Epub 2010 Oct 22. [PubMed:20967473 ]
    General function:
    Involved in monooxygenase 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 performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,8-cineole 2-exo-monooxygenase. The enzyme also hydroxylates etoposide.
    Gene Name:
    CYP3A4
    Uniprot ID:
    P08684
    Molecular weight:
    57255.585
    References
    1. Toth M, Bajnogel J, Egyed A, Drabant S, Tomlo J, Klebovich I: [Effect of tofisopam on CYP3A4 enzyme activity on human recombinant 3A4 supersome]. Acta Pharm Hung. 2005;75(4):195-8. [PubMed:16711396 ]

    PMID: 10452354

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