ROPINIROLE

First approved in 1997

Details

Stereochemistry	ACHIRAL
Molecular Formula	C16H24N2O
Molecular Weight	260.3746
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CCCN(CCC)CCC1=CC=CC2=C1CC(=O)N2

InChI

InChIKey=UHSKFQJFRQCDBE-UHFFFAOYSA-N

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)

HIDE SMILES / InChI

Description
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/020658s034lbl.pdf
Curator's Comment: description was created based on several sources, including http://reference.medscape.com/drug/requip-xl-ropinirole-343051 | https://www.drugs.com/cdi/ropinirole.html | https://www.drugbank.ca/drugs/DB00268

Ropinirole (INN; trade names Requip, Repreve, Ronirol, Adartrel) is a dopamine agonist of the non-ergoline class of medications, used in the treatment of Parkinson's disease and restless legs syndrome. 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 dopamine 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. Ropinirole 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. Ropinirole can cause nausea, dizziness, hallucinations, orthostatic hypotension, and sudden sleep attacks during the daytime. Unusual side effects specific to D3 agonists such as ropinirole and pramipexole can include hypersexuality, punding, and compulsive gambling, even in patients without a history of these behaviors.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Dopamine D2 receptor 297 Target ID: CHEMBL217 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17976986	Agonist 2678	83.0 nM [EC50]
Dopamine D3 receptor 91 Target ID: CHEMBL234 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20038106	Partial Agonist 290	19.2 nM [EC50]
Dopamine receptor 60 Target ID: CHEMBL2096905 Sources: https://www.ncbi.nlm.nih.gov/pubmed/4045928	Agonist 2678	100.0 nM [EC50]

Conditions

Condition	Modality	Highest Phase	Product
Parkinson's disease 226 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/020658s034lbl.pdf	Primary	Approved 8429	REQUIP Approved Use Parkinson's Disease Ropinirole tablets are indicated for the treatment of the signs and symptoms of idiopathic Parkinson's disease. The effectiveness of ropinirole tablet was demonstrated in randomized, controlled trials in patients with early Parkinson's disease who were not receiving concomitant L-dopa therapy as well as in patients with advanced disease on concomitant L-dopa (see CLINICAL PHARMACOLOGY: Clinical Trials). Restless Legs Syndrome Ropinirole tablets are indicated for the treatment of moderate-to-severe primary Restless Legs Syndrome (RLS). Key diagnostic criteria for RLS are: an urge to move the legs usually accompanied or caused by uncomfortable and unpleasant leg sensations; symptoms begin or worsen during periods of rest or inactivity such as lying or sitting; symptoms are partially or totally relieved by movement such as walking or stretching at least as long as the activity continues; and symptoms are worse or occur only in the evening or night. Difficulty falling asleep may frequently be associated with moderate-to-severe RLS. Launch Date 1997
Restless legs syndrome 16 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/020658s034lbl.pdf	Primary	Approved 8429	REQUIP Approved Use Parkinson's Disease Ropinirole tablets are indicated for the treatment of the signs and symptoms of idiopathic Parkinson's disease. The effectiveness of ropinirole tablet was demonstrated in randomized, controlled trials in patients with early Parkinson's disease who were not receiving concomitant L-dopa therapy as well as in patients with advanced disease on concomitant L-dopa (see CLINICAL PHARMACOLOGY: Clinical Trials). Restless Legs Syndrome Ropinirole tablets are indicated for the treatment of moderate-to-severe primary Restless Legs Syndrome (RLS). Key diagnostic criteria for RLS are: an urge to move the legs usually accompanied or caused by uncomfortable and unpleasant leg sensations; symptoms begin or worsen during periods of rest or inactivity such as lying or sitting; symptoms are partially or totally relieved by movement such as walking or stretching at least as long as the activity continues; and symptoms are worse or occur only in the evening or night. Difficulty falling asleep may frequently be associated with moderate-to-severe RLS. Launch Date 1997
Sexual dysfunction 2 Sources: https://clinicaltrials.gov/ct2/show/NCT00334048	Primary	Phase IV 63	REQUIP Approved Use Parkinson's Disease Ropinirole tablets are indicated for the treatment of the signs and symptoms of idiopathic Parkinson's disease. The effectiveness of ropinirole tablet was demonstrated in randomized, controlled trials in patients with early Parkinson's disease who were not receiving concomitant L-dopa therapy as well as in patients with advanced disease on concomitant L-dopa (see CLINICAL PHARMACOLOGY: Clinical Trials). Restless Legs Syndrome Ropinirole tablets are indicated for the treatment of moderate-to-severe primary Restless Legs Syndrome (RLS). Key diagnostic criteria for RLS are: an urge to move the legs usually accompanied or caused by uncomfortable and unpleasant leg sensations; symptoms begin or worsen during periods of rest or inactivity such as lying or sitting; symptoms are partially or totally relieved by movement such as walking or stretching at least as long as the activity continues; and symptoms are worse or occur only in the evening or night. Difficulty falling asleep may frequently be associated with moderate-to-severe RLS. Launch Date 1997

C_max

Value	Dose	Co-administered	Analyte	Population
5.01 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9578193	2 mg 3 times / day steady-state, oral dose: 2 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		ROPINIROLE HYDROCHLORIDE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED
6.53 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9578193	2 mg 3 times / day steady-state, oral dose: 2 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		ROPINIROLE HYDROCHLORIDE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
25.9 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9578193	2 mg 3 times / day steady-state, oral dose: 2 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		ROPINIROLE HYDROCHLORIDE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED
29.1 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9578193	2 mg 3 times / day steady-state, oral dose: 2 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		ROPINIROLE HYDROCHLORIDE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
6 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/020658Orig1s037lbl.pdf	unknown, oral		ROPINIROLE HYDROCHLORIDE plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
60% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/020658Orig1s037lbl.pdf	unknown, oral		ROPINIROLE HYDROCHLORIDE plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
50 mg 1 times / day steady, oral Highest studied dose Dose: 50 mg, 1 times / day Route: oral Route: steady Dose: 50 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/28442303	unhealthy n = 1 Health Status: unhealthy Condition: Parkinson's disease with severe dyskinesias Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/28442303	Sources: https://pubmed.ncbi.nlm.nih.gov/28442303
435 mg 1 times / day multiple, oral Overdose Dose: 435 mg, 1 times / day Route: oral Route: multiple Dose: 435 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/020658Orig1s037lbl.pdf Page: p. 18	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/020658Orig1s037lbl.pdf Page: p. 18	Other AEs: Nausea, Dizziness... Other AEs: Nausea Dizziness Claustrophobia Chorea Palpitations Asthenia Nightmares Hyperhidrosis Visual hallucinations Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/020658Orig1s037lbl.pdf Page: p. 18
0.5 mg 2 times / day steady, oral Recommended Dose: 0.5 mg, 2 times / day Route: oral Route: steady Dose: 0.5 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/020658Orig1s037lbl.pdf	unhealthy n = 157 Health Status: unhealthy Condition: Parkinson’s disease Population Size: 157 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/020658Orig1s037lbl.pdf	Disc. AE: Nausea, Dizziness... AEs leading to discontinuation/dose reduction: Nausea (2%) Dizziness (2%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/020658Orig1s037lbl.pdf
24 mg 1 times / day steady, oral Recommended Dose: 24 mg, 1 times / day Route: oral Route: steady Dose: 24 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/28442303	unhealthy n = 61 Health Status: unhealthy Condition: Parkinson's disease Population Size: 61 Sources: https://pubmed.ncbi.nlm.nih.gov/28442303	Sources: https://pubmed.ncbi.nlm.nih.gov/28442303

AEs

AE	Significance	Dose	Population
Asthenia		435 mg 1 times / day multiple, oral Overdose Dose: 435 mg, 1 times / day Route: oral Route: multiple Dose: 435 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/020658Orig1s037lbl.pdf Page: p. 18	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/020658Orig1s037lbl.pdf Page: p. 18
Chorea		435 mg 1 times / day multiple, oral Overdose Dose: 435 mg, 1 times / day Route: oral Route: multiple Dose: 435 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/020658Orig1s037lbl.pdf Page: p. 18	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/020658Orig1s037lbl.pdf Page: p. 18
Claustrophobia		435 mg 1 times / day multiple, oral Overdose Dose: 435 mg, 1 times / day Route: oral Route: multiple Dose: 435 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/020658Orig1s037lbl.pdf Page: p. 18	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/020658Orig1s037lbl.pdf Page: p. 18
Dizziness		435 mg 1 times / day multiple, oral Overdose Dose: 435 mg, 1 times / day Route: oral Route: multiple Dose: 435 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/020658Orig1s037lbl.pdf Page: p. 18	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/020658Orig1s037lbl.pdf Page: p. 18
Hyperhidrosis		435 mg 1 times / day multiple, oral Overdose Dose: 435 mg, 1 times / day Route: oral Route: multiple Dose: 435 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/020658Orig1s037lbl.pdf Page: p. 18	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/020658Orig1s037lbl.pdf Page: p. 18
Nausea		435 mg 1 times / day multiple, oral Overdose Dose: 435 mg, 1 times / day Route: oral Route: multiple Dose: 435 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/020658Orig1s037lbl.pdf Page: p. 18	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/020658Orig1s037lbl.pdf Page: p. 18
Nightmares		435 mg 1 times / day multiple, oral Overdose Dose: 435 mg, 1 times / day Route: oral Route: multiple Dose: 435 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/020658Orig1s037lbl.pdf Page: p. 18	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/020658Orig1s037lbl.pdf Page: p. 18
Palpitations		435 mg 1 times / day multiple, oral Overdose Dose: 435 mg, 1 times / day Route: oral Route: multiple Dose: 435 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/020658Orig1s037lbl.pdf Page: p. 18	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/020658Orig1s037lbl.pdf Page: p. 18
Visual hallucinations		435 mg 1 times / day multiple, oral Overdose Dose: 435 mg, 1 times / day Route: oral Route: multiple Dose: 435 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/020658Orig1s037lbl.pdf Page: p. 18	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/020658Orig1s037lbl.pdf Page: p. 18
Dizziness	2% Disc. AE	0.5 mg 2 times / day steady, oral Recommended Dose: 0.5 mg, 2 times / day Route: oral Route: steady Dose: 0.5 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/020658Orig1s037lbl.pdf	unhealthy n = 157 Health Status: unhealthy Condition: Parkinson’s disease Population Size: 157 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/020658Orig1s037lbl.pdf
Nausea	2% Disc. AE	0.5 mg 2 times / day steady, oral Recommended Dose: 0.5 mg, 2 times / day Route: oral Route: steady Dose: 0.5 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/020658Orig1s037lbl.pdf	unhealthy n = 157 Health Status: unhealthy Condition: Parkinson’s disease Population Size: 157 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/020658Orig1s037lbl.pdf

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:8888	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:8888
MolPort	MolPort-003-666-598	https://www.molport.com/shop/molecule-link/MolPort-003-666-598
ZINC	ZINC000000002041	http://zinc15.docking.org/substances/ZINC000000002041
eMolecules	902428	https://www.emolecules.com/cgi-bin/more?vid=902428

PubMed

Title	Date	PubMed
Sleep disorders in patients with Parkinson's disease: epidemiology and management.	2001	11463132
The Posturo-Locomotion-Manual Test. A simple method for the characterization of neurological movement disturbances.	2001	11347247
Dopamine agonists.	2001	11346030
Ropinirole versus bromocriptine for levodopa-induced complications in Parkinson's disease.	2001	11279719
Ropinirole for levodopa-induced complications in Parkinson's disease.	2001	11279718
Neostriatal muscarinic receptor subtypes involved in the generation of tremulous jaw movements in rodents implications for cholinergic involvement in parkinsonism.	2001 Apr 27	11392629
Antiparkinsonian drugs and "sleep attacks".	2001 Apr 3	11314438
Iontophoretic delivery of ropinirole hydrochloride: effect of current density and vehicle formulation.	2001 Dec	11785691
[Dopamine agonists situation in Parkinson disease].	2001 Dec 1-15	11785037
Possible applications for dopaminergic agents following traumatic brain injury: part 2.	2001 Feb	11277855
Literature alert.	2001 Jul	11898535
Adjunctive dopamine agonists in treatment-resistant bipolar II depression: an open case series.	2001 Jul	11518474
Long-duration effect and the postsynaptic compartment: study using a dopamine agonist with a short half-life.	2001 Mar	11295785
[Parkinson's disease].	2001 Mar 3	11268898
[Parkinson disease: diagnostic and therapeutic criteria].	2001 Mar 3	11268897
Newer dopamine agonists in the treatment of restless legs syndrome.	2001 May	11346069
Sleep attacks and antiparkinsonian drugs: a pilot prospective pharmacoepidemiologic study.	2001 May-Jun	11391132
Alterations in striatal neuropeptide mRNA produced by repeated administration of L-DOPA, ropinirole or bromocriptine correlate with dyskinesia induction in MPTP-treated common marmosets.	2002	12453478
Choosing the right dopamine agonist for patients with Parkinson's disease.	2002	12201621
'Sleep attacks' or 'unintended sleep episodes' occur with dopamine agonists: is this a class effect?	2002	12093305
Two advances in the management of Parkinson disease.	2002 Aug	12184472
A comparison of the progression of early Parkinson's disease in patients started on ropinirole or L-dopa: an 18F-dopa PET study.	2002 Dec	12486484
Effect of ropinirole on sleep onset: a randomized, placebo-controlled study in healthy volunteers.	2002 Feb 12	11839850
Restless legs syndrome: treatment with dopaminergic agents.	2002 Feb 26	11909990
Sleep attacks in patients taking dopamine agonists: review.	2002 Jun 22	12077032
Alopecia induced by dopamine agonists.	2002 Mar 12	11889256
Cabergoline, pramipexole and ropinirole used as monotherapy in early Parkinson's disease: an evidence-based comparison.	2003	12964891
Comparison of the risk of adverse events with pramipexole and ropinirole in patients with Parkinson's disease: a meta-analysis.	2003	12688834
Ropinirole as an adjunct to levodopa in the treatment of Parkinson's disease A short commentary.	2003 Jan	12528000
Slower progression of Parkinson's disease with ropinirole versus levodopa: The REAL-PET study.	2003 Jul	12838524
REAL and CALM: what have we learned?	2003 Jul	12815670
The initial drug treatment of older patients with Parkinson's disease - consider an agonist, but don't demonise dopa.	2003 May	12720606
Dihydroergocriptine in Parkinson's disease: clinical efficacy and comparison with other dopamine agonists.	2003 May	12713527

Patents

Sample Use Guides

In Vivo Use Guide

Parkinson Disease: 0.25 mg PO q8hr for 1 week initially, then increased weekly by 0.25 mg q8hr; if necessary, after week 4, may be increased weekly by 1.5 mg/day up to 9 mg/day, then increased weekly by 3 mg/day up to 24 mg/day Restless Leg Syndrome: 0.25 mg/day PO 1-3 hr before bedtime; after day 2, may be increased to 0.5 mg/day PO; at end of week 1, increased to 1 mg/day, then increased weekly by 0.5 mg/day up to 4 mg/day

Route of Administration: Oral

In Vitro Use Guide

Human SH-SY5Y neuroblastoma cells were grown to confluence in Dulbecco’s Modified Eagle’s media (DMEM) supplemented with 10% fetal calf serum, 100 mkg/mL penicillin, 100 mkg/mL streptomycin, 0.25 mkg/mL amphotericin B, and 0.01 mkM non-essential amino acids (Gibco Grand Island, NY, USA) and then sub-cultured for differentiation in 48 well Costar culture plates. For differentiation, the cells were grown in same media containing 10 mkM retinoic acid for 3 days; then the media was removed and replaced with media containing 160 nM of the phorbol ester 12-O-tetradecanoyl-phorbol-13-acetate (TPA) for 3 days of differentiation. The cells were then administered a range doses of pramipexole, ropinirole and S32504 (10 nM to 1 mM) in DMEM for three days prior to addition of 1 mM MPP+. Following transfer of MPP+ to the media cells were tested every 24 h for 72 h for the cytotoxicity of MPP+ as measured by the MTT and LDH assays which accurately measure different aspects of apoptosis. In addition, we tested for the neuroprotective effects of a fixed dose of each drug (50 mkM) and a range of doses of S32504 on MPP+ induced apoptosis, and the effects of ropinirole alone (1 mM) as measured by DNA laddering.

Name

Type

Language

ROPINIROLE

Official Name

English

Ropinirole [WHO-DD]

Common Name

English

ROPINIROLE [MI]

Common Name

English

NARAPIN

Common Name

English

SK&F 101468

Code

English

ROPITOR

Brand Name

English

ROPINIROLE [USAN]

Common Name

English

NSC-758917

Code

English

ROPINIROLE [VANDF]

Common Name

English

ropinirole [INN]

Common Name

English

SK&F-101468

Code

English

Classification Tree Code System Code

NCI_THESAURUS

C38149