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Identification
NameRopinirole
Accession NumberDB00268  (APRD00302)
Typesmall molecule
Groupsapproved, investigational
Description

Ropinirole is a non-ergoline dopamine agonist, manufactured by GlaxoSmithKline. It is used in the treatment of Parkinson’s disease, and is also one of two medications in the United States with an FDA-approved indication for the treatment of restless legs syndrome (the other being Pramipexole). [Wikipedia]

Structure
Thumb
Synonyms
SynonymLanguageCode
RopinirolSpanishINN
RopinirolumLatinINN
Salts
Name/CAS Structure Properties
Ropinirole Hydrochloride
Thumb
  • InChI Key: XDXHAEQXIBQUEZ-UHFFFAOYSA-N
  • Monoisotopic Mass: 296.165541139
  • Average Mass: 296.836
DBSALT000390
Brand names
NameCompany
AdartrelNot Available
ReQuipGlaxoSmithKline
ReQuip CRGlaxoSmithKline
ReQuip XLGlaxoSmithKline
RonirolNot Available
Brand mixturesNot Available
Categories
CAS number91374-21-9
WeightAverage: 260.3746
Monoisotopic: 260.1888634
Chemical FormulaC16H24N2O
InChI KeyInChIKey=UHSKFQJFRQCDBE-UHFFFAOYSA-N
InChI
InChI=1S/C16H24N2O/c1-3-9-18(10-4-2)11-8-13-6-5-7-15-14(13)12-16(19)17-15/h5-7H,3-4,8-12H2,1-2H3,(H,17,19)
IUPAC Name
4-[2-(dipropylamino)ethyl]-2,3-dihydro-1H-indol-2-one
SMILES
CCCN(CCC)CCC1=C2CC(=O)NC2=CC=C1
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassHeterocyclic Compounds
ClassIndoles and Derivatives
SubclassIndolines
Direct parentIndolines
Alternative parentsPhenethylamines; Secondary Carboxylic Acid Amides; Tertiary Amines; Polyamines; Carboxylic Acids
Substituentsbenzene; tertiary amine; secondary carboxylic acid amide; carboxamide group; carboxylic acid derivative; polyamine; carboxylic acid; amine; organonitrogen compound
Classification descriptionThis compound belongs to the indolines. These are compounds containing an indole moiety, which consists of pyrrolidine ring fused to benzene to form 2,3-dihydroindole.
Pharmacology
IndicationFor the treatment of the signs and symptoms of idiopathic Parkinson's disease. Also used for the treatment of restless legs syndrome.
PharmacodynamicsRopinirole is a nonergot dopamine agonist with high relative in vitro specificity and full intrinsic activity at the D2 subfamily of dopamine receptors, binding with higher affinity to D3 than to D2 or D4 receptor subtypes. The relevance of D3 receptor binding in Parkinson's disease is unknown. The mechanism of ropinirole-induced postural hypotension is presumed to be due to a D2 -mediated blunting of the noradrenergic response to standing and subsequent decrease in peripheral vascular resistance.
Mechanism of actionRopinirole binds the dopamine receptors D3 and D2. Although the precise mechanism of action of ropinirole as a treatment for Parkinson's disease is unknown, it is believed to be related to its ability to stimulate these receptors in the striatum. This conclusion is supported by electrophysiologic studies in animals that have demonstrated that ropinirole influences striatal neuronal firing rates via activation of dopamine receptors in the striatum and the substantia nigra, the site of neurons that send projections to the striatum.
AbsorptionAbsolute bioavailability is 55%, indicating a first pass effect. Food does not affect the extent of absorption.
Volume of distribution
  • 7.5 L/kg
  • 525 L
Protein binding40% bound to plasma proteins with a blood-to-plasma ratio of 1:1.
Metabolism

Hepatic. Ropinirole is extensively metabolized to inactive metabolites via N -despropylation and hydroxylation pathways, largely by the P450 isoenzyme CYP1A2. N-despropyl ropinirole is the predominant metabolite found in urine (40%), followed by the carboxylic acid metabolite (10%), and the glucuronide of the hydroxy metabolite (10%).

SubstrateEnzymesProduct
Ropinirole
    N-despropyl ropiniroleDetails
    Route of eliminationRopinirole is extensively metabolized by the liver to inactive metabolites, and less than 10% of the administered dose is excreted as unchanged drug in urine.
    Half life6 hours
    Clearance
    • 47 L/hr [after oral administration to Parkinson’s disease patients and patients with Restless Legs Syndrome]
    ToxicitySymptoms of overdose include agitation, chest pain, confusion, drowsiness, facial muscle movements, grogginess, increased jerkiness of movement, symptoms of low blood pressure (dizziness, light-headedness)upon standing, nausea, and vomiting.
    Affected organisms
    • Humans and other mammals
    PathwaysNot Available
    SNP Mediated EffectsNot Available
    SNP Mediated Adverse Drug ReactionsNot Available
    ADMET
    Predicted ADMET features
    Property Value Probability
    Human Intestinal Absorption + 1.0
    Blood Brain Barrier + 0.9971
    Caco-2 permeable + 0.6087
    P-glycoprotein substrate Substrate 0.7604
    P-glycoprotein inhibitor I Inhibitor 0.5458
    P-glycoprotein inhibitor II Non-inhibitor 0.8641
    Renal organic cation transporter Non-inhibitor 0.602
    CYP450 2C9 substrate Non-substrate 0.8593
    CYP450 2D6 substrate Non-substrate 0.9116
    CYP450 3A4 substrate Substrate 0.6903
    CYP450 1A2 substrate Non-inhibitor 0.9045
    CYP450 2C9 substrate Non-inhibitor 0.9071
    CYP450 2D6 substrate Inhibitor 0.8932
    CYP450 2C19 substrate Non-inhibitor 0.9025
    CYP450 3A4 substrate Non-inhibitor 0.8309
    CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.6959
    Ames test Non AMES toxic 0.7302
    Carcinogenicity Non-carcinogens 0.905
    Biodegradation Not ready biodegradable 0.9966
    Rat acute toxicity 2.6400 LD50, mol/kg Not applicable
    hERG inhibition (predictor I) Weak inhibitor 0.8959
    hERG inhibition (predictor II) Non-inhibitor 0.7066
    Pharmacoeconomics
    Manufacturers
    • Smithkline beecham corp dba glaxosmithkline
    • Glaxosmithkline
    • Alembic ltd
    • Corepharma llc
    • Glenmark generics ltd
    • Huahai us inc
    • Mylan pharmaceuticals inc
    • Roxane laboratories inc
    • Teva pharmaceuticals usa inc
    • Wockhardt ltd
    • Zydus pharmaceuticals usa inc
    Packagers
    Dosage forms
    FormRouteStrength
    Tablet, film coatedOral0.25 mg
    Tablet, film coatedOral1 mg
    Tablet, film coatedOral2 mg
    Tablet, film coatedOral3 mg
    Tablet, film coatedOral4 mg
    Tablet, film coatedOral5 mg
    Prices
    Unit descriptionCostUnit
    Requip XL 12 mg 24 Hour tablet14.92USDtablet
    Requip xl 12 mg tablet14.35USDtablet
    Requip XL 8 mg 24 Hour tablet8.96USDtablet
    Requip xl 6 mg tablet8.61USDtablet
    Requip xl 8 mg tablet8.61USDtablet
    Requip XL 4 mg 24 Hour tablet5.97USDtablet
    Requip xl 4 mg tablet5.74USDtablet
    Requip 5 mg Tablet3.87USDtablet
    Requip 3 mg tablet3.41USDtablet
    Requip 4 mg tablet3.41USDtablet
    Requip 5 mg tablet3.41USDtablet
    Requip 0.25 mg tablet3.29USDtablet
    Requip 0.5 mg tablet3.29USDtablet
    Requip 1 mg tablet3.29USDtablet
    Requip 2 mg tablet3.29USDtablet
    Requip xl 2 mg tablet2.87USDtablet
    Ropinirole hcl 3 mg tablet2.65USDtablet
    Ropinirole hcl 4 mg tablet2.65USDtablet
    Ropinirole hcl 5 mg tablet2.65USDtablet
    Ropinirole hcl 0.25 mg tablet2.55USDtablet
    Ropinirole hcl 0.5 mg tablet2.55USDtablet
    Ropinirole hcl 1 mg tablet2.55USDtablet
    Ropinirole hcl 2 mg tablet2.55USDtablet
    Co Ropinirole 5 mg Tablet1.8USDtablet
    Pms-Ropinirole 5 mg Tablet1.8USDtablet
    Ran-Ropinirole 5 mg Tablet1.8USDtablet
    Ropinirole 5 mg Tablet1.8USDtablet
    Requip 2 mg Tablet1.41USDtablet
    Requip 1 mg Tablet1.28USDtablet
    Co Ropinirole 2 mg Tablet0.65USDtablet
    Pms-Ropinirole 2 mg Tablet0.65USDtablet
    Ran-Ropinirole 2 mg Tablet0.65USDtablet
    Ropinirole 2 mg Tablet0.65USDtablet
    Co Ropinirole 1 mg Tablet0.59USDtablet
    Pms-Ropinirole 1 mg Tablet0.59USDtablet
    Ran-Ropinirole 1 mg Tablet0.59USDtablet
    Ropinirole 1 mg Tablet0.59USDtablet
    Requip 0.25 mg Tablet0.32USDtablet
    Co Ropinirole 0.25 mg Tablet0.15USDtablet
    Pms-Ropinirole 0.25 mg Tablet0.15USDtablet
    Ran-Ropinirole 0.25 mg Tablet0.15USDtablet
    Ropinirole 0.25 mg Tablet0.15USDtablet
    DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
    Patents
    CountryPatent NumberApprovedExpires (estimated)
    United States54221231995-06-062012-06-06
    Properties
    Statesolid
    Experimental Properties
    PropertyValueSource
    melting point243-250 °CNot Available
    water solubility133 mg/mLNot Available
    logP2.70ADLARD,M ET AL. (1995)
    Predicted Properties
    PropertyValueSource
    water solubility3.53e-01 g/lALOGPS
    logP3.16ALOGPS
    logP3.06ChemAxon
    logS-2.9ALOGPS
    pKa (strongest acidic)13.24ChemAxon
    pKa (strongest basic)10.17ChemAxon
    physiological charge1ChemAxon
    hydrogen acceptor count2ChemAxon
    hydrogen donor count1ChemAxon
    polar surface area32.34ChemAxon
    rotatable bond count7ChemAxon
    refractivity81.43ChemAxon
    polarizability31.19ChemAxon
    number of rings2ChemAxon
    bioavailability1ChemAxon
    rule of fiveYesChemAxon
    Ghose filterYesChemAxon
    Veber's ruleYesChemAxon
    MDDR-like ruleNoChemAxon
    Spectra
    SpectraNot Available
    References
    Synthesis Reference

    DrugSyn.org

    US4452808
    General ReferenceNot Available
    External Links
    ResourceLink
    KEGG CompoundC07564
    PubChem Compound5095
    PubChem Substance46507918
    ChemSpider4916
    ChEBI8888
    ChEMBLCHEMBL589
    Therapeutic Targets DatabaseDAP001515
    PharmGKBPA164749035
    Drug Product Database2232567
    RxListhttp://www.rxlist.com/cgi/generic/ropinirole.htm
    Drugs.comhttp://www.drugs.com/cdi/ropinirole.html
    PDRhealthhttp://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/req1372.shtml
    WikipediaRopinirole
    ATC CodesN04BC04
    AHFS Codes
    • 28:36.20.08
    PDB EntriesNot Available
    FDA labelshow(267 KB)
    MSDSshow(29.6 KB)
    Interactions
    Drug Interactions
    Drug
    CiprofloxacinCiprofloxacin may increase the effect and toxicity of ropinirole.
    DihydrocodeineDihydrocodeine may enhance the sedative effect of ropinirole. It is recommended to monitor therapy
    FluvoxamineIncreases the effect and toxicity of ropinirole
    PaliperidoneThe atypical antipsychotic agent, paliperidone, may decrease the therapeutic effect of the anti-Parkinson's agent, ropinirole. This interaction may be due to the dopamine antagonist properties of paliperidone. Consider an alternate antipsychotic in those with Parkinson's disease or consider using clozapine or quetiapine if an atypical antipsychotic is necessary.
    ThiothixeneThiothixene may antaonize the effects of the anti-Parkinsonian agent, Ropinirole. Consider alternate therapy or monitor for decreased effects of both agents.
    ZiprasidoneThe atypical antipsychotic, ziprasidone, may antagonize the effect of the dopamine agonist, ropinirole. Consider alternate therapy or monitor for worsening of movement disorder.
    ZuclopenthixolAntagonism may occur between zuclopenthixol, a dopamine D2 receptor antagonist, and ropinirole, a dopamine agonist. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of both agents if concurrent therapy is initiated, discontinued or dose(s) changed.
    Zuclopenthixol acetateAntagonism may occur between zuclopenthixol, a dopamine D2 receptor antagonist, and ropinirole, a dopamine agonist. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of both agents if concurrent therapy is initiated, discontinued or dose(s) changed.
    Zuclopenthixol decanoateAntagonism may occur between zuclopenthixol, a dopamine D2 receptor antagonist, and ropinirole, a dopamine agonist. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of both agents if concurrent therapy is initiated, discontinued or dose(s) changed.
    Food InteractionsNot Available

    1. D(3) dopamine receptor

    Kind: protein

    Organism: Human

    Pharmacological action: yes

    Actions: agonist

    Components

    Name UniProt ID Details
    D(3) dopamine receptor P35462 Details

    References:

    1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
    2. Kvernmo T, Houben J, Sylte I: Receptor-binding and pharmacokinetic properties of dopaminergic agonists. Curr Top Med Chem. 2008;8(12):1049-67. Pubmed
    3. Lam YW: Clinical pharmacology of dopamine agonists. Pharmacotherapy. 2000 Jan;20(1 Pt 2):17S-25S. Pubmed

    2. D(2) dopamine receptor

    Kind: protein

    Organism: Human

    Pharmacological action: yes

    Actions: agonist

    Components

    Name UniProt ID Details
    D(2) dopamine receptor P14416 Details

    References:

    1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
    2. de Mey C, Enterling D, Meineke I, Yeulet S: Interactions between domperidone and ropinirole, a novel dopamine D2-receptor agonist. Br J Clin Pharmacol. 1991 Oct;32(4):483-8. Pubmed
    3. Iida M, Miyazaki I, Tanaka K, Kabuto H, Iwata-Ichikawa E, Ogawa N: Dopamine D2 receptor-mediated antioxidant and neuroprotective effects of ropinirole, a dopamine agonist. Brain Res. 1999 Aug 14;838(1-2):51-9. Pubmed
    4. Kvernmo T, Houben J, Sylte I: Receptor-binding and pharmacokinetic properties of dopaminergic agonists. Curr Top Med Chem. 2008;8(12):1049-67. Pubmed
    5. Lam YW: Clinical pharmacology of dopamine agonists. Pharmacotherapy. 2000 Jan;20(1 Pt 2):17S-25S. Pubmed
    6. Matsukawa N, Maki M, Yasuhara T, Hara K, Yu G, Xu L, Kim KM, Morgan JC, Sethi KD, Borlongan CV: Overexpression of D2/D3 receptors increases efficacy of ropinirole in chronically 6-OHDA-lesioned Parkinsonian rats. Brain Res. 2007 Jul 30;1160:113-23. Epub 2007 May 26. Pubmed

    3. D(4) dopamine receptor

    Kind: protein

    Organism: Human

    Pharmacological action: unknown

    Actions: agonist

    Components

    Name UniProt ID Details
    D(4) dopamine receptor P21917 Details

    References:

    1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
    2. Kvernmo T, Houben J, Sylte I: Receptor-binding and pharmacokinetic properties of dopaminergic agonists. Curr Top Med Chem. 2008;8(12):1049-67. Pubmed

    4. 5-hydroxytryptamine receptor 1A

    Kind: protein

    Organism: Human

    Pharmacological action: unknown

    Actions: agonist

    Components

    Name UniProt ID Details
    5-hydroxytryptamine receptor 1A P08908 Details

    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

    5. 5-hydroxytryptamine receptor 1D

    Kind: protein

    Organism: Human

    Pharmacological action: unknown

    Actions: agonist

    Components

    Name UniProt ID Details
    5-hydroxytryptamine receptor 1D P28221 Details

    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

    6. 5-hydroxytryptamine receptor 2B

    Kind: protein

    Organism: Human

    Pharmacological action: unknown

    Actions: agonist

    Components

    Name UniProt ID Details
    5-hydroxytryptamine receptor 2B P41595 Details

    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

    7. D(1A) dopamine receptor

    Kind: protein

    Organism: Human

    Pharmacological action: unknown

    Actions: agonist

    Components

    Name UniProt ID Details
    D(1A) dopamine receptor P21728 Details

    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

    8. D(1B) dopamine receptor

    Kind: protein

    Organism: Human

    Pharmacological action: unknown

    Actions: agonist

    Components

    Name UniProt ID Details
    D(1B) dopamine receptor P21918 Details

    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

    9. 5-hydroxytryptamine receptor 1B

    Kind: protein

    Organism: Human

    Pharmacological action: unknown

    Actions: agonist

    Components

    Name UniProt ID Details
    5-hydroxytryptamine receptor 1B P28222 Details

    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

    10. 5-hydroxytryptamine receptor 2A

    Kind: protein

    Organism: Human

    Pharmacological action: unknown

    Actions: agonist

    Components

    Name UniProt ID Details
    5-hydroxytryptamine receptor 2A P28223 Details

    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

    11. 5-hydroxytryptamine receptor 2C

    Kind: protein

    Organism: Human

    Pharmacological action: unknown

    Actions: agonist

    Components

    Name UniProt ID Details
    5-hydroxytryptamine receptor 2C P28335 Details

    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

    12. Alpha-2A adrenergic receptor

    Kind: protein

    Organism: Human

    Pharmacological action: unknown

    Actions: agonist

    Components

    Name UniProt ID Details
    Alpha-2A adrenergic receptor P08913 Details

    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

    13. Alpha-2B adrenergic receptor

    Kind: protein

    Organism: Human

    Pharmacological action: unknown

    Actions: agonist

    Components

    Name UniProt ID Details
    Alpha-2B adrenergic receptor P18089 Details

    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

    14. Alpha-2C adrenergic receptor

    Kind: protein

    Organism: Human

    Pharmacological action: unknown

    Actions: agonist

    Components

    Name UniProt ID Details
    Alpha-2C adrenergic receptor P18825 Details

    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

    1. Cytochrome P450 1A2

    Kind: protein

    Organism: Human

    Pharmacological action: unknown

    Actions: substrate inhibitor

    Components

    Name UniProt ID Details
    Cytochrome P450 1A2 P05177 Details

    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
    2. 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. Epub 2009 Nov 24. Pubmed
    3. Lexicomp

    2. Cytochrome P450 3A4

    Kind: protein

    Organism: Human

    Pharmacological action: unknown

    Actions: substrate

    Components

    Name UniProt ID Details
    Cytochrome P450 3A4 P08684 Details

    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
    2. 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. Epub 2009 Nov 24. Pubmed

    3. Cytochrome P450 2D6

    Kind: protein

    Organism: Human

    Pharmacological action: unknown

    Actions: inhibitor

    Components

    Name UniProt ID Details
    Cytochrome P450 2D6 P10635 Details

    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
    2. 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. Epub 2009 Nov 24. Pubmed
    3. Lexicomp

    Comments
    Drug created on June 13, 2005 07:24 / Updated on October 08, 2013 14:25