Posted inUncategorized

Rotigotine

July 24, 2017
Common Name

Rotigotine Description

Rotigotine (Neupro) is a non-ergoline dopamine agonist indicated for the treatment of Parkinsons disease (PD) and restless legs syndrome (RLS) in Europe and the United States. It is formliated as a once-daily transdermal patch which provides a slow and constant supply of the drug over the course of 24 hours. Like other dopamine agonists, rotigotine has been shown to possess antidepressant effects and may be usefli in the treatment of depression as well. Rotigotine was developed by Aderis Pharmaceuticals. In 1998, Aderis licensed worldwide development and commercialization rights for rotigotine to the German pharmaceutical company Schwarz Pharma (today a subsidiary of the Belgian company UCB S.A.). The drug has been approved by the EMEA for use in Europe in 2006 and is today being sold in several European countries. In 2007, the Neupro patch was approved by the Food and Drug Administration (FDA) as the first transdermal treatment of Parkinsons disease in the United States. However, as of 2008, Schwarz Pharma has recalled all Neupro patches in the United States and some in Europe because of problems with the delivery mechanism. Rotigotine has been authorized as a treatment for RLS since August 2008. Structure

MOLSDF3D-SDFPDBSMILESInChI View 3D Structure

Synonyms

Value Source 2-(N-N-Propyl-N-2-thienylethylamino)-5-hydroxytetralinMeSH N 0437, (R)-IsomerMeSH N 0437, Hydrochloride, (S)-isomerMeSH NeuproMeSH N 0437, Hydrochloride, (R)-isomerMeSH Rotigotine CDSMeSH N 0437, (+-)-IsomerMeSH N 0437, (-)-IsomerMeSH

Chemical Formlia

C19H25NOS Average Molecliar Weight

315.473 Monoisotopic Molecliar Weight

315.165685117 IUPAC Name

6-{propyl[2-(thiophen-2-yl)ethyl]amino}-5,6,7,8-tetrahydronaphthalen-1-ol Traditional Name

rotigotine CAS Registry Number

92206-54-7 SMILES

CCCN(CCC1=CC=CS1)C1CCC2=C(C1)C=CC=C2O

InChI Identifier

InChI=1S/C19H25NOS/c1-2-11-20(12-10-17-6-4-13-22-17)16-8-9-18-15(14-16)5-3-7-19(18)21/h3-7,13,16,21H,2,8-12,14H2,1H3

InChI Key

KFQYTPMOWPVWEJ-UHFFFAOYSA-N Chemical Taxonomy Description

This compound belongs to the class of chemical entities known as tetralins. These are polycyclic aromatic compounds containing a tetralin moiety, which consists of a benzene fused to a cyclohexane. Kingdom

Chemical entities Super Class

Organic compounds Class

Benzenoids Sub Class

Tetralins Direct Parent

Tetralins Alternative Parents

  • Aralkylamines
  • 1-hydroxy-4-unsubstituted benzenoids
  • 1-hydroxy-2-unsubstituted benzenoids
  • Thiophenes
  • Heteroaromatic compounds
  • Trialkylamines
  • Organopnictogen compounds
  • Organooxygen compounds
  • Hydrocarbon derivatives

    • Substituents

  • Tetralin
  • 1-hydroxy-4-unsubstituted benzenoid
  • 1-hydroxy-2-unsubstituted benzenoid
  • Aralkylamine
  • Thiophene
  • Heteroaromatic compound
  • Tertiary amine
  • Tertiary aliphatic amine
  • Organoheterocyclic compound
  • Hydrocarbon derivative
  • Organopnictogen compound
  • Organic oxygen compound
  • Organic nitrogen compound
  • Organooxygen compound
  • Organonitrogen compound
  • Amine
  • Aromatic heteropolycyclic compound

    • Molecliar Framework

    Aromatic heteropolycyclic compounds External Descriptors

    Not Available Ontology Status

    Expected but not Quantified Origin

  • Drug

    • Biofunction

  • Antidyskinetics
  • Antiparkinson Agents
  • Dopamine Agonists

    • Application

  • Pharmaceutical

    • Cellliar locations

  • Membrane

    • Physical Properties State

    Solid Experimental Properties

    Property Value Reference Melting PointNot AvailableNot Available Boiling PointNot AvailableNot Available Water Solubility9.04e-03 g/LNot Available LogP4.70BIOBYTE STARLIST (2009)

    Predicted Properties

    Property Value Source Water Solubility0.009 mg/mLALOGPS logP5.01ALOGPS logP4.34ChemAxon logS-4.5ALOGPS pKa (Strongest Acidic)10.03ChemAxon pKa (Strongest Basic)10.97ChemAxon Physiological Charge1ChemAxon Hydrogen Acceptor Count2ChemAxon Hydrogen Donor Count1ChemAxon Polar Surface Area23.47 Å2ChemAxon Rotatable Bond Count6ChemAxon Refractivity94.56 m3·mol-1ChemAxon Polarizability37.17 Å3ChemAxon Number of Rings3ChemAxon Bioavailability1ChemAxon Rlie of FiveYesChemAxon Ghose FilterYesChemAxon Vebers RlieYesChemAxon MDDR-like RlieYesChemAxon

    Spectra Spectra

    Not 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 DB05271

  • 21059682

    • details UrineExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB05271

  • 21059682

    • details

    Abnormal Concentrations

    Not Available Associated Disorders and Diseases Disease References

    None Associated OMIM IDs

    None External Links DrugBank ID

    DB05271 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

    51867 KEGG Compound ID

    Not Available BioCyc ID

    Not Available BiGG ID

    Not Available Wikipedia Link

    Rotigotine NuGOwiki Link

    HMDB15615 Metagene Link

    HMDB15615 METLIN ID

    Not Available PubChem Compound

    57537 PDB ID

    Not Available ChEBI ID

    Not Available

    Product: Methylthiouracil

    References Synthesis Reference Not Available Material Safety Data Sheet (MSDS) Not Available General References
    1. Giladi N, Boroojerdi B, Korczyn AD, Burn DJ, Clarke CE, Schapira AH: Rotigotine transdermal patch in early Parkinsons disease: a randomized, double-blind, controlled study versus placebo and ropinirole. Mov Disord. 2007 Dec;22(16):2398-404. [PubMed:17935234 ]
    2. Chen JJ, Swope DM, Dashtipour K, Lyons KE: Transdermal rotigotine: a clinically innovative dopamine-receptor agonist for the management of Parkinsons disease. Pharmacotherapy. 2009 Dec;29(12):1452-67. doi: 10.1592/phco.29.12.1452. [PubMed:19947805 ]
    3. Perez-Lloret S, Rey MV, Ratti PL, Rascol O: Rotigotine transdermal patch for the treatment of Parkinsons Disease. Fundam Clin Pharmacol. 2013 Feb;27(1):81-95. doi: 10.1111/j.1472-8206.2012.01028.x. Epub 2012 Feb 9. [PubMed:22320451 ]
    4. de Biase S, Merlino G, Lorenzut S, Valente M, Gigli GL: ADMET considerations for restless leg syndrome drug treatments. Expert Opin Drug Metab Toxicol. 2012 Oct;8(10):1247-61. doi: 10.1517/17425255.2012.708023. Epub 2012 Jul 18. [PubMed:22808933 ]

    Enzymes

    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. Kvernmo T, Houben J, Sylte I: Receptor-binding and pharmacokinetic properties of dopaminergic agonists. Curr Top Med Chem. 2008;8(12):1049-67. [PubMed:18691132 ]
    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. Kvernmo T, Houben J, Sylte I: Receptor-binding and pharmacokinetic properties of dopaminergic agonists. Curr Top Med Chem. 2008;8(12):1049-67. [PubMed:18691132 ]
    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. Kvernmo T, Houben J, Sylte I: Receptor-binding and pharmacokinetic properties of dopaminergic agonists. Curr Top Med Chem. 2008;8(12):1049-67. [PubMed:18691132 ]
    General function:
    Involved in G-protein coupled receptor protein signaling pathway
    Specific function:
    This is one of the five types (D1 to D5) of receptors for dopamine. The activity of this receptor is mediated by G proteins which inhibit adenylyl cyclase
    Gene Name:
    DRD2
    Uniprot ID:
    P14416
    Molecular weight:
    50618.9
    References
    1. Kvernmo T, Houben J, Sylte I: Receptor-binding and pharmacokinetic properties of dopaminergic agonists. Curr Top Med Chem. 2008;8(12):1049-67. [PubMed:18691132 ]
    General function:
    Involved in G-protein coupled receptor protein signaling pathway
    Specific function:
    This is one of the five types (D1 to D5) of receptors for dopamine. The activity of this receptor is mediated by G proteins which inhibit adenylyl cyclase
    Gene Name:
    DRD4
    Uniprot ID:
    P21917
    Molecular weight:
    48359.9
    References
    1. Kvernmo T, Houben J, Sylte I: Receptor-binding and pharmacokinetic properties of dopaminergic agonists. Curr Top Med Chem. 2008;8(12):1049-67. [PubMed:18691132 ]
    General function:
    Involved in G-protein coupled receptor protein signaling pathway
    Specific function:
    This is one of the several different receptors for 5- hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. The activity of this receptor is mediated by G proteins that inhibit adenylate cyclase activity
    Gene Name:
    HTR1A
    Uniprot ID:
    P08908
    Molecular weight:
    46106.3
    References
    1. Kvernmo T, Houben J, Sylte I: Receptor-binding and pharmacokinetic properties of dopaminergic agonists. Curr Top Med Chem. 2008;8(12):1049-67. [PubMed:18691132 ]
    General function:
    Involved in G-protein coupled receptor protein signaling pathway
    Specific function:
    This is one of the five types (D1 to D5) of receptors for dopamine. The activity of this receptor is mediated by G proteins which inhibit adenylyl cyclase. Promotes cell proliferation
    Gene Name:
    DRD3
    Uniprot ID:
    P35462
    Molecular weight:
    44224.3
    References
    1. Kvernmo T, Houben J, Sylte I: Receptor-binding and pharmacokinetic properties of dopaminergic agonists. Curr Top Med Chem. 2008;8(12):1049-67. [PubMed:18691132 ]
    General function:
    Involved in G-protein coupled receptor protein signaling pathway
    Specific function:
    This is one of the five types (D1 to D5) of receptors for dopamine. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase
    Gene Name:
    DRD1
    Uniprot ID:
    P21728
    Molecular weight:
    49292.8
    References
    1. Kvernmo T, Houben J, Sylte I: Receptor-binding and pharmacokinetic properties of dopaminergic agonists. Curr Top Med Chem. 2008;8(12):1049-67. [PubMed:18691132 ]
    General function:
    Involved in G-protein coupled receptor protein signaling pathway
    Specific function:
    This is one of the five types (D1 to D5) of receptors for dopamine. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase
    Gene Name:
    DRD5
    Uniprot ID:
    P21918
    Molecular weight:
    52950.5
    References
    1. Kvernmo T, Houben J, Sylte I: Receptor-binding and pharmacokinetic properties of dopaminergic agonists. Curr Top Med Chem. 2008;8(12):1049-67. [PubMed:18691132 ]

    PMID: 16162831

    Last updated on