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Rasagiline

July 24, 2017
Common Name

Rasagiline Description

Rasagiline is only found in individuals that have used or taken this drug. It is an irreversible inhibitor of monoamine oxidase and is used as a monotherapy in early Parkinsons disease or as an adjunct therapy in more advanced cases.The precise mechanisms of action of rasagiline is unknown. One mechanism is believed to be related to its MAO-B inhibitory activity, which causes an increase in extracellliar levels of dopamine in the striatum. The elevated dopamine level and subsequent increased dopaminergic activity are likely to mediate rasagilines beneficial effects seen in models of dopaminergic motor dysfunction. Structure

MOLSDF3D-SDFPDBSMILESInChI View 3D Structure

Synonyms

Value Source (1R)-N-Propargylindan-1-amineChEBI (R)-Indan-1-yl-prop-2-ynyl-amineChEBI (R)-N-2-Propynyl-1-indanamineChEBI RASChEBI 2,3-dihydro-N-2-Propynyl-1H-inden-1-amine-(1R)-hydrochlorideMeSH AzilectMeSH N-2-Propynyl-1-indanamineMeSH N-Propargyl-1-aminoindan mesylateMeSH TVP 101MeSH TVP-101MeSH Rasagiline hydrochlorideMeSH

Chemical Formlia

C12H13N Average Molecliar Weight

171.2383 Monoisotopic Molecliar Weight

171.104799421 IUPAC Name

(1R)-N-(prop-2-yn-1-yl)-2,3-dihydro-1H-inden-1-amine Traditional Name

rasagiline CAS Registry Number

136236-51-6 SMILES

C#CCN[C@@H]1CCC2=CC=CC=C12

InChI Identifier

InChI=1S/C12H13N/c1-2-9-13-12-8-7-10-5-3-4-6-11(10)12/h1,3-6,12-13H,7-9H2/t12-/m1/s1

InChI Key

RUOKEQAAGRXIBM-GFCCVEGCSA-N Chemical Taxonomy Description

This compound belongs to the class of organic compounds known as indanes. These are compounds containing an indane moiety, which consists of a cyclopentane fused to a benzene ring. Kingdom

Organic compounds Super Class

Benzenoids Class

Indanes Sub Class

Not Available Direct Parent

Indanes Alternative Parents

  • Aralkylamines
  • Dialkylamines
  • Acetylides
  • Organopnictogen compounds
  • Hydrocarbon derivatives

    • Substituents

  • Indane
  • Aralkylamine
  • Acetylide
  • Secondary amine
  • Secondary aliphatic amine
  • Organic nitrogen compound
  • Organopnictogen compound
  • Hydrocarbon derivative
  • Organonitrogen compound
  • Amine
  • Aromatic homopolycyclic compound

    • Molecliar Framework

    Aromatic homopolycyclic compounds External Descriptors

  • terminal acetylenic compound (CHEBI:63620 )
  • secondary amine (CHEBI:63620 )
  • indanes (CHEBI:63620 )

    • Ontology Status

    Expected but not Quantified Origin

  • Drug

    • Biofunction

  • Monoamine Oxidase Inhibitors
  • Neuroprotective Agents

    • Application

  • Pharmaceutical

    • Cellliar locations

  • Cytoplasm
  • Membrane

    • Physical Properties State

    Solid Experimental Properties

    Property Value Reference Melting PointNot AvailableNot Available Boiling PointNot AvailableNot Available Water Solubility2.49e-02 g/LNot Available LogPNot AvailableNot Available

    Predicted Properties

    Property Value Source Water Solubility0.025 mg/mLALOGPS logP2.26ALOGPS logP2.3ChemAxon logS-3.8ALOGPS pKa (Strongest Basic)8.69ChemAxon Physiological Charge1ChemAxon Hydrogen Acceptor Count1ChemAxon Hydrogen Donor Count1ChemAxon Polar Surface Area12.03 Å2ChemAxon Rotatable Bond Count2ChemAxon Refractivity54.47 m3·mol-1ChemAxon Polarizability20.25 Å3ChemAxon Number of Rings2ChemAxon 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 DB01367

  • 21059682

    • details UrineExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB01367

  • 21059682

    • details

    Abnormal Concentrations

    Not Available Associated Disorders and Diseases Disease References

    None Associated OMIM IDs

    None External Links DrugBank ID

    DB01367 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

    2314553 KEGG Compound ID

    Not Available BioCyc ID

    Not Available BiGG ID

    Not Available Wikipedia Link

    Rasagiline NuGOwiki Link

    HMDB15454 Metagene Link

    HMDB15454 METLIN ID

    Not Available PubChem Compound

    3052776 PDB ID

    Not Available ChEBI ID

    63620

    Product: Fingolimod

    References Synthesis Reference Not Available Material Safety Data Sheet (MSDS) Not Available General References
    1. Leegwater-Kim J, Bortan E: The role of rasagiline in the treatment of Parkinsons disease. Clin Interv Aging. 2010 May 25;5:149-56. [PubMed:20517484 ]
    2. Chen JJ, Swope DM, Dashtipour K: Comprehensive review of rasagiline, a second-generation monoamine oxidase inhibitor, for the treatment of Parkinsons disease. Clin Ther. 2007 Sep;29(9):1825-49. [PubMed:18035186 ]
    3. Weinreb O, Amit T, Bar-Am O, Youdim MB: Rasagiline: a novel anti-Parkinsonian monoamine oxidase-B inhibitor with neuroprotective activity. Prog Neurobiol. 2010 Nov;92(3):330-44. doi: 10.1016/j.pneurobio.2010.06.008. Epub 2010 Jun 19. [PubMed:20600573 ]

    Enzymes

    General function:
    Involved in oxidoreductase activity
    Specific function:
    Catalyzes the oxidative deamination of biogenic and xenobiotic amines and has important functions in the metabolism of neuroactive and vasoactive amines in the central nervous system and peripheral tissues. MAOB preferentially degrades benzylamine and phenylethylamine.
    Gene Name:
    MAOB
    Uniprot ID:
    P27338
    Molecular weight:
    58762.475
    References
    1. Naoi M, Maruyama W: Functional mechanism of neuroprotection by inhibitors of type B monoamine oxidase in Parkinsons disease. Expert Rev Neurother. 2009 Aug;9(8):1233-50. doi: 10.1586/ern.09.68. [PubMed:19673610 ]
    2. Uzun M, Alp R, Uzlu E, Alp S, Citil M, Topcu B, Erdogan HM: Investigation of oral selegiline and rasagiline administration on QT interval in conscious rabbits. Eur Rev Med Pharmacol Sci. 2009 Mar-Apr;13(2):95-8. [PubMed:19499843 ]
    3. Youdim MB, Weinstock M: Molecular basis of neuroprotective activities of rasagiline and the anti-Alzheimer drug TV3326 [(N-propargyl-(3R)aminoindan-5-YL)-ethyl methyl carbamate]. Cell Mol Neurobiol. 2001 Dec;21(6):555-73. [PubMed:12043833 ]
    4. Chau KY, Cooper JM, Schapira AH: Rasagiline protects against alpha-synuclein induced sensitivity to oxidative stress in dopaminergic cells. Neurochem Int. 2010 Nov;57(5):525-9. doi: 10.1016/j.neuint.2010.06.017. Epub 2010 Jul 17. [PubMed:20624440 ]
    5. Weinreb O, Amit T, Bar-Am O, Youdim MB: Rasagiline: a novel anti-Parkinsonian monoamine oxidase-B inhibitor with neuroprotective activity. Prog Neurobiol. 2010 Nov;92(3):330-44. doi: 10.1016/j.pneurobio.2010.06.008. Epub 2010 Jun 19. [PubMed:20600573 ]
    6. Youdim MB, Bar Am O, Yogev-Falach M, Weinreb O, Maruyama W, Naoi M, Amit T: Rasagiline: neurodegeneration, neuroprotection, and mitochondrial permeability transition. J Neurosci Res. 2005 Jan 1-15;79(1-2):172-9. [PubMed:15573406 ]
    7. Leegwater-Kim J, Bortan E: The role of rasagiline in the treatment of Parkinsons disease. Clin Interv Aging. 2010 May 25;5:149-56. [PubMed:20517484 ]
    8. Chen JJ, Swope DM, Dashtipour K: Comprehensive review of rasagiline, a second-generation monoamine oxidase inhibitor, for the treatment of Parkinsons disease. Clin Ther. 2007 Sep;29(9):1825-49. [PubMed:18035186 ]
    9. 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 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 oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N3-demethylation. Also acts in the metabolism of aflatoxin B1 and acetaminophen. Participates in the bioactivation of carcinogenic aromatic and heterocyclic amines. Catalizes the N-hydroxylation of heterocyclic amines and the O-deethylation of phenacetin.
    Gene Name:
    CYP1A2
    Uniprot ID:
    P05177
    Molecular weight:
    58406.915
    References
    1. Lecht S, Haroutiunian S, Hoffman A, Lazarovici P: Rasagiline – a novel MAO B inhibitor in Parkinsons disease therapy. Ther Clin Risk Manag. 2007 Jun;3(3):467-74. [PubMed:18488080 ]
    2. Leegwater-Kim J, Bortan E: The role of rasagiline in the treatment of Parkinsons disease. Clin Interv Aging. 2010 May 25;5:149-56. [PubMed:20517484 ]
    3. Chen JJ, Swope DM, Dashtipour K: Comprehensive review of rasagiline, a second-generation monoamine oxidase inhibitor, for the treatment of Parkinsons disease. Clin Ther. 2007 Sep;29(9):1825-49. [PubMed:18035186 ]
    4. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
    General function:
    Involved in regulation of apoptosis
    Specific function:
    Suppresses apoptosis in a variety of cell systems including factor-dependent lymphohematopoietic and neural cells. Regulates cell death by controlling the mitochondrial membrane permeability. Appears to function in a feedback loop system with caspases. Inhibits caspase activity either by preventing the release of cytochrome c from the mitochondria and/or by binding to the apoptosis-activating factor (APAF-1)
    Gene Name:
    BCL2
    Uniprot ID:
    P10415
    Molecular weight:
    26265.7
    References
    1. Youdim MB, Weinstock M: Molecular basis of neuroprotective activities of rasagiline and the anti-Alzheimer drug TV3326 [(N-propargyl-(3R)aminoindan-5-YL)-ethyl methyl carbamate]. Cell Mol Neurobiol. 2001 Dec;21(6):555-73. [PubMed:12043833 ]
    2. Akao Y, Maruyama W, Yi H, Shamoto-Nagai M, Youdim MB, Naoi M: An anti-Parkinsons disease drug, N-propargyl-1(R)-aminoindan (rasagiline), enhances expression of anti-apoptotic bcl-2 in human dopaminergic SH-SY5Y cells. Neurosci Lett. 2002 Jun 28;326(2):105-8. [PubMed:12057839 ]
    3. Maruyama W, Akao Y, Carrillo MC, Kitani K, Youdium MB, Naoi M: Neuroprotection by propargylamines in Parkinsons disease: suppression of apoptosis and induction of prosurvival genes. Neurotoxicol Teratol. 2002 Sep-Oct;24(5):675-82. [PubMed:12200198 ]
    4. Youdim MB, Amit T, Falach-Yogev M, Bar Am O, Maruyama W, Naoi M: The essentiality of Bcl-2, PKC and proteasome-ubiquitin complex activations in the neuroprotective-antiapoptotic action of the anti-Parkinson drug, rasagiline. Biochem Pharmacol. 2003 Oct 15;66(8):1635-41. [PubMed:14555244 ]
    5. Bar-Am O, Weinreb O, Amit T, Youdim MB: Regulation of Bcl-2 family proteins, neurotrophic factors, and APP processing in the neurorescue activity of propargylamine. FASEB J. 2005 Nov;19(13):1899-901. Epub 2005 Sep 7. [PubMed:16148027 ]

    PMID: 8100350

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