Identification

Name
Ropinirole
Accession Number
DB00268  (APRD00302)
Type
Small Molecule
Groups
Approved, Investigational
Description

Ropinirole, also known as ReQuip, is a non-ergoline dopamine agonist used in Parkinson's disease and restless legs syndrome [Label], [3]. It is manufactured by GlaxoSmithKline Pharmaceuticals. Ropinirole was initially approved in 1997 by the FDA [Label] for the management of Parkinson's disease. In 2005, it was the first drug approved in the US for the management of primary moderate to severe restless legs syndrome [3].

In 2008, the extended-release capsules of ropinirole were approved, allowing for less frequent dosing, therefore increased compliance, and offering a similar side effect profile and efficacy to previous formulations of ropinirole [4].

Structure
Thumb
Synonyms
  • Ropinirol
  • Ropinirole
  • Ropinirolum
External IDs
SK&F 101468 / SK&F-101468
Product Ingredients
IngredientUNIICASInChI Key
Ropinirole HydrochlorideD7ZD41RZI991374-20-8XDXHAEQXIBQUEZ-UHFFFAOYSA-N
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Act RopiniroleTablet5 mgOralActavis Pharma Company2009-07-22Not applicableCanada
Act RopiniroleTablet2 mgOralActavis Pharma Company2009-07-22Not applicableCanada
Act RopiniroleTablet1 mgOralActavis Pharma Company2009-07-22Not applicableCanada
Act RopiniroleTablet0.25 mgOralActavis Pharma Company2009-07-22Not applicableCanada
RequipTablet1 mgOralGlaxosmithkline Inc1997-09-25Not applicableCanada
RequipTablet, film coated5 mg/1OralGlaxo Wellcome SA1997-10-102019-03-31Us
RequipTablet, film coated5 mg/1OralGlaxosmithkline Inc1997-10-102019-03-31Us00007 4894 20 nlmimage10 c718e3d7
RequipTablet, film coated3 mg/1OralPhysicians Total Care, Inc.2006-02-202008-12-31Us
RequipTablet, film coated1 mg/1OralGlaxo Wellcome SA1997-10-012019-07-31Us
RequipTablet, film coated0.25 mg/1OralPhysicians Total Care, Inc.2007-10-182008-12-31Us
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Apo-ropiniroleTablet0.25 mgOralApotex CorporationNot applicableNot applicableCanada
Apo-ropiniroleTablet2.0 mgOralApotex CorporationNot applicableNot applicableCanada
Apo-ropiniroleTablet5.0 mgOralApotex CorporationNot applicableNot applicableCanada
Apo-ropiniroleTablet1.0 mgOralApotex CorporationNot applicableNot applicableCanada
Apo-ropiniroleTablet4.0 mgOralApotex CorporationNot applicableNot applicableCanada
Apo-ropiniroleTablet0.5 mgOralApotex CorporationNot applicableNot applicableCanada
Apo-ropiniroleTablet3.0 mgOralApotex CorporationNot applicableNot applicableCanada
Dom-ropiniroleTablet0.25 mgOralDominion PharmacalNot applicableNot applicableCanada
Dom-ropiniroleTablet5.0 mgOralDominion PharmacalNot applicableNot applicableCanada
Dom-ropiniroleTablet2.0 mgOralDominion PharmacalNot applicableNot applicableCanada
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
RequipRopinirole Hydrochloride + Ropinirole Hydrochloride + Ropinirole HydrochlorideTablet, film coatedOralGlaxoSmithKline2006-10-062006-10-06Us
RequipRopinirole Hydrochloride + Ropinirole Hydrochloride + Ropinirole HydrochlorideTablet, film coatedOralGlaxoSmithKline2006-10-062006-10-06Us
RequipRopinirole Hydrochloride + Ropinirole Hydrochloride + Ropinirole HydrochlorideTablet, film coatedOralGlaxoSmithKline2006-10-062006-10-06Us
International/Other Brands
Adartrel / ReQuip CR (GlaxoSmithKline) / Ronirol
Categories
UNII
030PYR8953
CAS number
91374-21-9
Weight
Average: 260.3746
Monoisotopic: 260.1888634
Chemical Formula
C16H24N2O
InChI Key
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

Pharmacology

Indication

For the treatment of the signs and symptoms of Parkinson's disease and for the treatment of primary moderate-severe restless legs syndrome [Label].

Associated Conditions
Pharmacodynamics

Effects on Parkinson's and restless leg syndrome

This drug promotes the relief or improvement of symptoms of Parkinson's or restless leg syndrome by stimulatory actions on dopamine receptors, which regulate movement.

Effects on blood pressure

Clinical experience with dopamine agonists, including ropinirole, suggests an association with impaired abilities in regulating blood pressure with resulting orthostatic hypotension, especially with patients undergoing dose escalation. In some patients in clinical studies, blood pressure changes were associated with orthostatic symptoms, bradycardia, and, in one case in a healthy volunteer, transient sinus arrest accompanied by syncope [Label]. The mechanism of orthostatic hypotension caused by ropinirole is assumed to be due to a D2-mediated blunting of noradrenergic response to a standing position, followed by a decrease in peripheral vascular resistance. Nausea is also a frequent symptom which accompanies orthostatic signs and symptoms [Label].

Effects on prolactin

At oral doses as low as 0.2 mg, ropinirole suppressed serum prolactin concentrations in healthy male volunteers. Ropinirole had no dose-related effect on ECG wave form and rhythm in young, healthy, male volunteers in the range of 0.01 to 2.5 mg [Label].

Effects on QT interval

Ropinirole had no dose- or exposure-related effect on average QT intervals in healthy male and female volunteers at doses up to 4 mg/day. The effect of ropinirole on QTc intervals at higher exposures reached either due to drug interactions, hepatic dysfunction, or at higher doses has not been adequately evaluated [Label].

Mechanism of action

Ropinirole is a non-ergoline dopamine agonist. Ropinirole has the highest affinity at the D3 receptors, which are concentrated in the limbic areas of the brain and may be responsible for some of the neuropsychiatric effects [4]. The exact mechanism of action of ropinirole as a treatment for Parkinson’s disease is unknown, however, it is believed to be related to its ability to selectively stimulate dopamine D2 receptors within the caudate-putamen system in the brain. This system affects body movement. Negligible affinity is seen for ropinirole at α2 adrenoreceptors in the periphery and 5HT-1 receptor. Ropinirole has no affinity at the D1-like receptors, benzodiazepine or GABA receptors [4].

The precise mechanism of action of ropinirole as a treatment for Restless Legs Syndrome is unknown, however, it is believed to be related to its ability to stimulate dopamine receptors [Label].

TargetActionsOrganism
AD(3) dopamine receptor
agonist
Humans
UD(4) dopamine receptor
agonist
Humans
UAlpha adrenergic receptor
antagonist
Humans
AD(2) dopamine receptor
agonist
Humans
Absorption

Ropinirole is rapidly absorbed after oral administration, reaching peak concentration in approximately 1 to 2 hours [Label], [5].

Absolute bioavailability was 45% to 55%, suggesting approximately 50% hepatic first-pass effect [Label]. The bioavailability of ropinirole prolonged release compared to the immediate release tablets is about 100% [2].

Ingestion of food does not affect the absorption of ropinirole, although its Tmax was increased by 2.5 hours and its Cmax was reduced by approximately 25% when the drug is taken with a high-fat meal [Label].

Volume of distribution

Ropinirole is found to be widely distributed throughout the body, with an apparent volume of distribution of 7.5 L/kg [Label].

Protein binding

40% bound to plasma proteins with a blood-to-plasma ratio of 1:1 [Label].

Metabolism

Ropinirole is heavily metabolized by the liver. The most important metabolic pathways are N­ despropylation and hydroxylation to form the N-despropyl metabolite and hydroxy metabolites [Label], both of which are inactive [4].

The N-despropyl metabolite is then converted to carbamyl glucuronide, carboxylic acid, and N-despropyl hydroxy metabolites. Following this process, the hydroxy metabolite of ropinirole is glucuronidated at a rapid rate [Label].

In vitro studies show that the major cytochrome P450 enzyme involved in the metabolism of ropinirole is CYP1A2 [Label], [5].

Route of elimination

The majority of the absorbed dose is cleared by the liver [4].

In clinical trials, more than 88% of a radiolabeled dose was recovered in urine [Label]. Less than 10% of the administered dose is excreted as unchanged drug in urine. N-despropyl ropinirole is the major metabolite found in the urine (40%), followed by the carboxylic acid metabolite (10%), and the glucuronide of the hydroxy metabolite (10%) [Label].

Half life

Approximately 6 hours [Label], [5].

Clearance

The clearance of ropinirole after oral administration is 47 L/h [Label].

Toxicity

Overdose

Symptoms 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 [Label].

Carcinogenicity

Two-year carcinogenicity studies of ropinirole were performed on animal models at oral doses of 5, 15, and 50 mg/kg/day and in rats at oral doses of 1.5, 15, and 50 mg/kg/day. There was an increase in testicular Leydig cell adenomas at all doses tested in rats. The hormonal mechanisms thought to be involved in the development of these tumors in rats are not considered relevant to humans. In mice, there was an increase in benign uterine endometrial polyps at a dose of 50 mg/kg/day. The highest dose not associated with this observation (15 mg/kg/day) is three times the maximum recommended human dose on a mg/m2 basis [Label].

Mutagenesis

Ropinirole was not found to be mutagenic or clastogenic during in vitro assays, or in the in vivo mouse micronucleus test [Label].

Effects on reproduction

When given to female rats prior to and during mating and throughout pregnancy, ropinirole led to disruption of implantation at oral doses of 20 mg/kg/day (8 times the MRHD on a mg/m2 basis) or higher. This effect in rats is believed to be due to the prolactin-lowering effects of ropinirole.

Use in Pregnancy

Pregnancy Category C. There are no sufficient and well-controlled studies done in pregnant women. In animal reproduction studies, ropinirole has demonstrated adverse effects on embryo-fetal development, including teratogenicity [Label].

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
3-isobutyl-1-methyl-7H-xanthineThe serum concentration of 3-isobutyl-1-methyl-7H-xanthine can be increased when it is combined with Ropinirole.
4-Methoxyamphetamine4-Methoxyamphetamine may increase the sedative activities of Ropinirole.
6-O-benzylguanineThe serum concentration of 6-O-benzylguanine can be increased when it is combined with Ropinirole.
7-DeazaguanineThe serum concentration of 7-Deazaguanine can be increased when it is combined with Ropinirole.
7-Nitroindazole7-Nitroindazole may increase the sedative activities of Ropinirole.
7,9-DimethylguanineThe serum concentration of 7,9-Dimethylguanine can be increased when it is combined with Ropinirole.
8-azaguanineThe serum concentration of 8-azaguanine can be increased when it is combined with Ropinirole.
8-chlorotheophyllineThe serum concentration of 8-chlorotheophylline can be increased when it is combined with Ropinirole.
9-DeazaguanineThe serum concentration of 9-Deazaguanine can be increased when it is combined with Ropinirole.
9-MethylguanineThe serum concentration of 9-Methylguanine can be increased when it is combined with Ropinirole.
Food Interactions
Not Available

References

Synthesis Reference
US4452808
General References
  1. Matheson AJ, Spencer CM: Ropinirole: a review of its use in the management of Parkinson's disease. Drugs. 2000 Jul;60(1):115-37. doi: 10.2165/00003495-200060010-00007. [PubMed:10929932]
  2. Nashatizadeh MM, Lyons KE, Pahwa R: A review of ropinirole prolonged release in Parkinson's disease. Clin Interv Aging. 2009;4:179-86. Epub 2009 May 14. [PubMed:19503779]
  3. Kushida CA: Ropinirole for the treatment of restless legs syndrome. Neuropsychiatr Dis Treat. 2006 Dec;2(4):407-19. [PubMed:19412490]
  4. Shill HA, Stacy M: Update on ropinirole in the treatment of Parkinson's disease. Neuropsychiatr Dis Treat. 2009;5:33-6. Epub 2009 Apr 8. [PubMed:19557097]
  5. Kaye CM, Nicholls B: Clinical pharmacokinetics of ropinirole. Clin Pharmacokinet. 2000 Oct;39(4):243-54. doi: 10.2165/00003088-200039040-00001. [PubMed:11069211]
  6. Drug Approval Package, FDA [Link]
  7. Ropinirole extended release FDA label [File]
  8. UK labeling, Ropinirole [File]
External Links
Human Metabolome Database
HMDB0014413
KEGG Drug
D08489
KEGG Compound
C07564
PubChem Compound
5095
PubChem Substance
46507918
ChemSpider
4916
BindingDB
50020680
ChEBI
8888
ChEMBL
CHEMBL589
Therapeutic Targets Database
DAP001515
PharmGKB
PA164749035
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Ropinirole
ATC Codes
N04BC04 — Ropinirole
AHFS Codes
  • 28:36.20.08 — Nonergot-derivative Dopamine Receptor Agonists
FDA label
Download (796 KB)
MSDS
Download (29.6 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedNot AvailableHealthy Volunteers2
1CompletedNot AvailablePharmacokinetic Study2
1CompletedTreatmentHealthy Volunteers2
1CompletedTreatmentParkinson's Disease (PD)1
1CompletedTreatmentRestless Legs Syndrome (RLS)2
1, 2RecruitingTreatmentParkinson's Disease (PD)1
1, 2RecruitingTreatmentIdiopathic hyperprolactinemic disorder / Prolactinoma1
2CompletedTreatmentCerebrovascular Accidents / Hemiparesis1
2CompletedTreatmentDependence, Cocaine1
2CompletedTreatmentFibromyalgia Syndrome, Primary1
2CompletedTreatmentParkinson's Disease (PD)1
2CompletedTreatmentPeripheral T-Cell Lymphoma (PTCL)1
2Not Yet RecruitingTreatmentEnd Stage Renal Disease (ESRD) / Restless Legs Syndrome (RLS)1
2TerminatedTreatmentRestless Legs Syndrome (RLS)1
2Unknown StatusTreatmentUnverricht-Lundborg Syndrome1
3CompletedTreatmentIdiopathic Parkinson's Disease1
3CompletedTreatmentModerate to Severe Idiopathic Restless Legs Syndrome (RLS) / Restless Legs Syndrome (RLS)1
3CompletedTreatmentParkinson's Disease (PD)5
3CompletedTreatmentRestless Legs Syndrome (RLS)6
3Not Yet RecruitingTreatmentEnd Stage Renal Disease (ESRD) / Restless Legs Syndrome (RLS)1
3TerminatedTreatmentLymphoma, Large-Cell, Diffuse1
3Unknown StatusTreatmentParkinson's Disease (PD)1
4CompletedDiagnosticParkinson's Disease (PD)1
4CompletedTreatmentBipolar Disorder (BD)1
4CompletedTreatmentParkinson's Disease (PD)1
4CompletedTreatmentRestless Legs Syndrome (RLS)1
4CompletedTreatmentSexual Dysfunctions1
4Enrolling by InvitationSupportive CareLiver Cirrhosis / Muscle Cramps1
4Unknown StatusTreatmentBipolar Disorder (BD) / Major Depressive Disorder (MDD)1
Not AvailableCompletedNot AvailableRestless Legs Syndrome (RLS)1
Not AvailableCompletedTreatmentParkinson's Disease (PD) / Restless Legs Syndrome (RLS)2
Not AvailableRecruitingNot AvailableAtypical Parkinson Disease / Corticobasal Degeneration / Gait, Frontal / Multiple System Atrophy (MSA) / Parkinson's Disease (PD) / Parkinsonian Disorders / Progressive Supranuclear Palsy (PSP)1

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
  • Amerisource Health Services Corp.
  • A-S Medication Solutions LLC
  • Atlantic Biologicals Corporation
  • Bryant Ranch Prepack
  • Cadila Healthcare Ltd.
  • Cardinal Health
  • Corepharma LLC
  • GlaxoSmithKline Inc.
  • Glenmark Generics Ltd.
  • Heartland Repack Services LLC
  • Heritage Pharmaceuticals
  • Innoviant Pharmacy Inc.
  • Kaiser Foundation Hospital
  • Lake Erie Medical and Surgical Supply
  • Major Pharmaceuticals
  • Mckesson Corp.
  • Murfreesboro Pharmaceutical Nursing Supply
  • Mylan
  • Nucare Pharmaceuticals Inc.
  • PD-Rx Pharmaceuticals Inc.
  • Physicians Total Care Inc.
  • Rebel Distributors Corp.
  • Resource Optimization and Innovation LLC
  • Roxane Labs
  • Stat Rx Usa
  • Teva Pharmaceutical Industries Ltd.
  • Vangard Labs Inc.
  • Wockhardt Ltd.
  • Zydus Pharmaceuticals
Dosage forms
FormRouteStrength
TabletOral1 mg
TabletOral2 mg
TabletOral5 mg
TabletOral3.0 mg
TabletOral4.0 mg
TabletOral0.25 mg
TabletOral0.5 mg
TabletOral1.0 mg
TabletOral2.0 mg
TabletOral5.0 mg
Tablet, film coatedOral
Tablet, film coatedOral0.25 mg/1
Tablet, film coatedOral0.5 mg/1
Tablet, film coatedOral1 mg/1
Tablet, film coatedOral2 mg/1
Tablet, film coatedOral3 mg/1
Tablet, film coatedOral4 mg/1
Tablet, film coated, extended releaseOral2 mg/1
TabletOral4 mg/1
TabletOral5 mg/1
TabletOral0.25 mg/1
TabletOral0.5 mg/1
TabletOral1 mg/1
TabletOral2 mg/1
TabletOral3 mg/1
Tablet, coatedOral0.25 mg/1
Tablet, coatedOral0.5 mg/1
Tablet, coatedOral1 mg/1
Tablet, coatedOral2 mg/1
Tablet, coatedOral3 mg/1
Tablet, coatedOral4 mg/1
Tablet, coatedOral5 mg/1
Tablet, film coatedOral5 mg/1
Tablet, film coated, extended releaseOral12 mg/1
Tablet, film coated, extended releaseOral3 mg/1
Tablet, film coated, extended releaseOral4 mg/1
Tablet, film coated, extended releaseOral6 mg/1
Tablet, film coated, extended releaseOral8 mg/1
Prices
Unit descriptionCostUnit
Requip XL 12 mg 24 Hour tablet14.92USD tablet
Requip xl 12 mg tablet14.35USD tablet
Requip XL 8 mg 24 Hour tablet8.96USD tablet
Requip xl 6 mg tablet8.61USD tablet
Requip xl 8 mg tablet8.61USD tablet
Requip XL 4 mg 24 Hour tablet5.97USD tablet
Requip xl 4 mg tablet5.74USD tablet
Requip 5 mg Tablet3.87USD tablet
Requip 3 mg tablet3.41USD tablet
Requip 4 mg tablet3.41USD tablet
Requip 5 mg tablet3.41USD tablet
Requip 0.25 mg tablet3.29USD tablet
Requip 0.5 mg tablet3.29USD tablet
Requip 1 mg tablet3.29USD tablet
Requip 2 mg tablet3.29USD tablet
Requip xl 2 mg tablet2.87USD tablet
Ropinirole hcl 3 mg tablet2.65USD tablet
Ropinirole hcl 4 mg tablet2.65USD tablet
Ropinirole hcl 5 mg tablet2.65USD tablet
Ropinirole hcl 0.25 mg tablet2.55USD tablet
Ropinirole hcl 0.5 mg tablet2.55USD tablet
Ropinirole hcl 1 mg tablet2.55USD tablet
Ropinirole hcl 2 mg tablet2.55USD tablet
Co Ropinirole 5 mg Tablet1.8USD tablet
Pms-Ropinirole 5 mg Tablet1.8USD tablet
Ran-Ropinirole 5 mg Tablet1.8USD tablet
Ropinirole 5 mg Tablet1.8USD tablet
Requip 2 mg Tablet1.41USD tablet
Requip 1 mg Tablet1.28USD tablet
Co Ropinirole 2 mg Tablet0.65USD tablet
Pms-Ropinirole 2 mg Tablet0.65USD tablet
Ran-Ropinirole 2 mg Tablet0.65USD tablet
Ropinirole 2 mg Tablet0.65USD tablet
Co Ropinirole 1 mg Tablet0.59USD tablet
Pms-Ropinirole 1 mg Tablet0.59USD tablet
Ran-Ropinirole 1 mg Tablet0.59USD tablet
Ropinirole 1 mg Tablet0.59USD tablet
Requip 0.25 mg Tablet0.32USD tablet
Co Ropinirole 0.25 mg Tablet0.15USD tablet
Pms-Ropinirole 0.25 mg Tablet0.15USD tablet
Ran-Ropinirole 0.25 mg Tablet0.15USD tablet
Ropinirole 0.25 mg Tablet0.15USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US5422123No1995-06-062012-06-06Us
US7927624No2011-04-192021-12-02Us
US8303986No2012-11-062021-04-12Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)243-250 °CFDA label
boiling point (°C)410.5±45.0 °C at 760 mmHghttp://www.chemspider.com/Chemical-Structure.4916.html
water solubility133 mg/mLFDA label
logP3.06http://www.t3db.ca/toxins/T3D2731
logS-2.9http://www.t3db.ca/toxins/T3D2731
pKa10.17http://www.t3db.ca/toxins/T3D2731
Predicted Properties
PropertyValueSource
Water Solubility0.353 mg/mLALOGPS
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 Area32.34 Å2ChemAxon
Rotatable Bond Count7ChemAxon
Refractivity81.43 m3·mol-1ChemAxon
Polarizability31.19 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.9971
Caco-2 permeable+0.6087
P-glycoprotein substrateSubstrate0.7604
P-glycoprotein inhibitor IInhibitor0.5458
P-glycoprotein inhibitor IINon-inhibitor0.8641
Renal organic cation transporterNon-inhibitor0.602
CYP450 2C9 substrateNon-substrate0.8593
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateSubstrate0.6903
CYP450 1A2 substrateNon-inhibitor0.9045
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorInhibitor0.8932
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-inhibitor0.8309
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.6959
Ames testNon AMES toxic0.7302
CarcinogenicityNon-carcinogens0.905
BiodegradationNot ready biodegradable0.9966
Rat acute toxicity2.6400 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8959
hERG inhibition (predictor II)Non-inhibitor0.7066
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-03di-0190000000-7e072cf65f341641938c
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-03di-3960000000-47d2311adfeeacf4062d
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-0006-7900000000-0891c66db163729a5360
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-0a4i-0090000000-88c0fa3d93090a0d06c6
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-0pb9-3590000000-8fb5fc766313ee6bbd9e
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-0k96-9400000000-f1b50dacd59a9bfe90b7

Taxonomy

Description
This compound belongs to the class of organic compounds known as indolines. These are compounds containing an indole moiety, which consists of pyrrolidine ring fused to benzene to form 2,3-dihydroindole.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Indoles and derivatives
Sub Class
Indolines
Direct Parent
Indolines
Alternative Parents
Phenethylamines / Aralkylamines / Trialkylamines / Secondary carboxylic acid amides / Lactams / Amino acids and derivatives / Azacyclic compounds / Organopnictogen compounds / Organic oxides / Hydrocarbon derivatives
show 1 more
Substituents
Dihydroindole / Phenethylamine / Aralkylamine / Benzenoid / Amino acid or derivatives / Carboxamide group / Lactam / Secondary carboxylic acid amide / Tertiary aliphatic amine / Tertiary amine
show 12 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
tertiary amine, indolones (CHEBI:8888)

Targets

Details
1. D(3) dopamine receptor
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Agonist
General Function
G-protein coupled amine receptor activity
Specific Function
Dopamine receptor whose activity is mediated by G proteins which inhibit adenylyl cyclase. Promotes cell proliferation.
Gene Name
DRD3
Uniprot ID
P35462
Uniprot Name
D(3) dopamine receptor
Molecular Weight
44224.335 Da
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]
  2. Lam YW: Clinical pharmacology of dopamine agonists. Pharmacotherapy. 2000 Jan;20(1 Pt 2):17S-25S. [PubMed:10641988]
  3. Nashatizadeh MM, Lyons KE, Pahwa R: A review of ropinirole prolonged release in Parkinson's disease. Clin Interv Aging. 2009;4:179-86. Epub 2009 May 14. [PubMed:19503779]
  4. Shill HA, Stacy M: Update on ropinirole in the treatment of Parkinson's disease. Neuropsychiatr Dis Treat. 2009;5:33-6. Epub 2009 Apr 8. [PubMed:19557097]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Agonist
General Function
Sh3 domain binding
Specific Function
Dopamine receptor responsible for neuronal signaling in the mesolimbic system of the brain, an area of the brain that regulates emotion and complex behavior. Its activity is mediated by G proteins ...
Gene Name
DRD4
Uniprot ID
P21917
Uniprot Name
D(4) dopamine receptor
Molecular Weight
48359.86 Da
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
  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:18691132]
  3. Shill HA, Stacy M: Update on ropinirole in the treatment of Parkinson's disease. Neuropsychiatr Dis Treat. 2009;5:33-6. Epub 2009 Apr 8. [PubMed:19557097]
Kind
Protein group
Organism
Humans
Pharmacological action
Unknown
Actions
Antagonist
General Function
Protein heterodimerization activity
Specific Function
This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) prot...

Components:
References
  1. Shill HA, Stacy M: Update on ropinirole in the treatment of Parkinson's disease. Neuropsychiatr Dis Treat. 2009;5:33-6. Epub 2009 Apr 8. [PubMed:19557097]
  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:18691132]
Details
4. D(2) dopamine receptor
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Agonist
General Function
Potassium channel regulator activity
Specific Function
Dopamine receptor whose activity is mediated by G proteins which inhibit adenylyl cyclase.
Gene Name
DRD2
Uniprot ID
P14416
Uniprot Name
D(2) dopamine receptor
Molecular Weight
50618.91 Da
References
  1. 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:1683559]
  2. 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:10446316]
  3. 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]
  4. Lam YW: Clinical pharmacology of dopamine agonists. Pharmacotherapy. 2000 Jan;20(1 Pt 2):17S-25S. [PubMed:10641988]
  5. 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:17573046]
  6. Shill HA, Stacy M: Update on ropinirole in the treatment of Parkinson's disease. Neuropsychiatr Dis Treat. 2009;5:33-6. Epub 2009 Apr 8. [PubMed:19557097]
  7. Requip FDA label [File]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
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 un...
Gene Name
CYP1A2
Uniprot ID
P05177
Uniprot Name
Cytochrome P450 1A2
Molecular Weight
58293.76 Da
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]
  2. Wynalda MA, Wienkers LC: Assessment of potential interactions between dopamine receptor agonists and various human cytochrome P450 enzymes using a simple in vitro inhibition screen. Drug Metab Dispos. 1997 Oct;25(10):1211-4. [PubMed:9321526]
  3. Kaye CM, Nicholls B: Clinical pharmacokinetics of ropinirole. Clin Pharmacokinet. 2000 Oct;39(4):243-54. doi: 10.2165/00003088-200039040-00001. [PubMed:11069211]
  4. Kushida CA: Ropinirole for the treatment of restless legs syndrome. Neuropsychiatr Dis Treat. 2006 Dec;2(4):407-19. [PubMed:19412490]
  5. Ropinrole FDA label [File]

Drug created on June 13, 2005 07:24 / Updated on February 18, 2019 20:23