U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ACHIRAL
Molecular Formula C16H24N2O.ClH
Molecular Weight 296.836
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ROPINIROLE HYDROCHLORIDE

SMILES

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

InChI

InChIKey=XDXHAEQXIBQUEZ-UHFFFAOYSA-N
InChI=1S/C16H24N2O.ClH/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);1H

HIDE SMILES / InChI

Molecular Formula ClH
Molecular Weight 36.461
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Molecular Formula C16H24N2O
Molecular Weight 260.3746
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
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.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
83.0 nM [EC50]
19.2 nM [EC50]
100.0 nM [EC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
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

8.746272E11
Primary
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

8.746272E11
Primary
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

8.746272E11
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
5.01 ng/mL
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
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

AUC

ValueDoseCo-administeredAnalytePopulation
25.9 ng × h/mL
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
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
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
6 h
unknown, oral
ROPINIROLE HYDROCHLORIDE plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
60%
unknown, oral
ROPINIROLE HYDROCHLORIDE plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse 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:
unhealthy
n = 1
Health Status: unhealthy
Condition: Parkinson's disease with severe dyskinesias
Population Size: 1
Sources:
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: Page: p. 18
unhealthy
Other AEs: Nausea, Dizziness...
Other AEs:
Nausea
Dizziness
Claustrophobia
Chorea
Palpitations
Asthenia
Nightmares
Hyperhidrosis
Visual hallucinations
Sources: 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:
unhealthy
n = 157
Health Status: unhealthy
Condition: Parkinson’s disease
Population Size: 157
Sources:
Disc. AE: Nausea, Dizziness...
AEs leading to
discontinuation/dose reduction:
Nausea (2%)
Dizziness (2%)
Sources:
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:
unhealthy
n = 61
Health Status: unhealthy
Condition: Parkinson's disease
Population Size: 61
Sources:
AEs

AEs

AESignificanceDosePopulation
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: Page: p. 18
unhealthy
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: Page: p. 18
unhealthy
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: Page: p. 18
unhealthy
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: Page: p. 18
unhealthy
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: Page: p. 18
unhealthy
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: Page: p. 18
unhealthy
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: Page: p. 18
unhealthy
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: Page: p. 18
unhealthy
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: Page: p. 18
unhealthy
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:
unhealthy
n = 157
Health Status: unhealthy
Condition: Parkinson’s disease
Population Size: 157
Sources:
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:
unhealthy
n = 157
Health Status: unhealthy
Condition: Parkinson’s disease
Population Size: 157
Sources:
PubMed

PubMed

TitleDatePubMed
Sleep disorders in patients with Parkinson's disease: epidemiology and management.
2001
Ropinirole for levodopa-induced complications in Parkinson's disease.
2001
Neostriatal muscarinic receptor subtypes involved in the generation of tremulous jaw movements in rodents implications for cholinergic involvement in parkinsonism.
2001 Apr 27
Antiparkinsonian drugs and "sleep attacks".
2001 Apr 3
Iontophoretic delivery of ropinirole hydrochloride: effect of current density and vehicle formulation.
2001 Dec
[Dopamine agonists situation in Parkinson disease].
2001 Dec 1-15
Efficacy and tolerability of dopamine agonists in a parkinsonian population.
2001 Feb
Antiparkinsonian activity and dyskinesia risk of ropinirole and L-DOPA combination therapy in drug naïve MPTP-lesioned common marmosets (Callithrix jacchus).
2001 Jul
Treatment of early onset Parkinson's disease with ropinirole.
2001 Mar
[Parkinson disease: diagnostic and therapeutic criteria].
2001 Mar 3
Sleep attacks and antiparkinsonian drugs: a pilot prospective pharmacoepidemiologic study.
2001 May-Jun
Randomized clinical trials with added rescue medication: some approaches to their analysis and interpretation.
2001 Oct 30
Sleep disorders in Parkinson's disease: epidemiology and management.
2002
DA agonists -- non-ergot derivatives: ropinirole: management of Parkinson's disease.
2002
Clinical pharmacokinetic and pharmacodynamic properties of drugs used in the treatment of Parkinson's disease.
2002
A six-month multicentre, double-blind, bromocriptine-controlled study of the safety and efficacy of ropinirole in the treatment of patients with Parkinson's disease not optimally controlled by L-dopa.
2002 Apr
Two advances in the management of Parkinson disease.
2002 Aug
[The usefulness of dopaminergic drugs in traumatic brain injury].
2002 Aug 16-31
Behavioral and neurochemical effects of dopaminergic drugs in models of brain injury.
2002 Jun
Alopecia induced by dopamine agonists.
2002 Mar 12
Ropinirole for the treatment of tremor in early Parkinson's disease.
2002 May
Do dopamine agonists or levodopa modify Parkinson's disease progression?
2002 Nov
Dopamine agonist monotherapy in Parkinson's disease.
2002 Nov 30
An evidence-based review of dopamine receptor agonists in the treatment of Parkinson's disease.
2002 Oct
Do dopaminergic agents increase the daytime sleep propensity? Article reviewed: Effect of ropinirole on sleep onset. A randomized, placebo-controlled study in healthy volunteers.
2002 Sep
Cabergoline, pramipexole and ropinirole used as monotherapy in early Parkinson's disease: an evidence-based comparison.
2003
Comparison of the risk of adverse events with pramipexole and ropinirole in patients with Parkinson's disease: a meta-analysis.
2003
[Sexual delinquency and Parkinson's disease].
2003 Apr
Ropinirole as an adjunct to levodopa in the treatment of Parkinson's disease: a 16-week bromocriptine controlled study.
2003 Jan
Slower progression of Parkinson's disease with ropinirole versus levodopa: The REAL-PET study.
2003 Jul
The initial drug treatment of older patients with Parkinson's disease - consider an agonist, but don't demonise dopa.
2003 May
High-dose ropinirole in advanced Parkinson's disease with severe dyskinesias.
2003 May-Jun
Current treatment options for restless legs syndrome.
2003 Oct
Patents

Sample Use Guides

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
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.
Substance Class Chemical
Created
by admin
on Fri Dec 16 18:24:54 UTC 2022
Edited
by admin
on Fri Dec 16 18:24:54 UTC 2022
Record UNII
D7ZD41RZI9
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
ROPINIROLE HYDROCHLORIDE
JAN   MART.   MI   ORANGE BOOK   USAN   USP-RS   VANDF   WHO-DD  
USAN  
Official Name English
ROPINIROLE HYDROCHLORIDE [MI]
Common Name English
4-[2-(Dipropylamino)ethyl]-2-indolinone monohydrochloride
Systematic Name English
ROPINIROLE HYDROCHLORIDE [USAN]
Common Name English
ROPINIROLE (AS HYDROCHLORIDE)
Common Name English
ROPINIROLE HYDROCHLORIDE [VANDF]
Common Name English
2H-INDOL-2-ONE, 4-(2-(DIPROPYLAMINO)ETHYL)-1,3-DIHYDRO-, MONOHYDROCHLORIDE
Systematic Name English
ROPINIROLE HYDROCHLORIDE [MART.]
Common Name English
SK&F 101468-A
Code English
ROPINIROLE HCL
Common Name English
ROPINIROLE HYDROCHLORIDE [ORANGE BOOK]
Common Name English
ROPINIROLE HYDROCHLORIDE [JAN]
Common Name English
Ropinirole hydrochloride [WHO-DD]
Common Name English
ROPINIROLE HYDROCHLORIDE [USP-RS]
Common Name English
4-(2-(DIPROPYLAMINO)ETHYL)-1,3-DIHYDRO-2H-INDOL-2-ONE MONOHYDROCHLORIDE
Systematic Name English
ROPINIROLE HYDROCHLORIDE [EP MONOGRAPH]
Common Name English
ROPINIROLE HYDROCHLORIDE [USP MONOGRAPH]
Common Name English
SK&F-101468-A
Code English
SK&F-101468A
Common Name English
REQUIP
Brand Name English
Classification Tree Code System Code
NCI_THESAURUS C38149
Created by admin on Fri Dec 16 18:24:54 UTC 2022 , Edited by admin on Fri Dec 16 18:24:54 UTC 2022
Code System Code Type Description
PUBCHEM
68727
Created by admin on Fri Dec 16 18:24:54 UTC 2022 , Edited by admin on Fri Dec 16 18:24:54 UTC 2022
PRIMARY
USAN
EE-30
Created by admin on Fri Dec 16 18:24:54 UTC 2022 , Edited by admin on Fri Dec 16 18:24:54 UTC 2022
PRIMARY
EVMPD
SUB15144MIG
Created by admin on Fri Dec 16 18:24:54 UTC 2022 , Edited by admin on Fri Dec 16 18:24:54 UTC 2022
PRIMARY
CAS
91374-20-8
Created by admin on Fri Dec 16 18:24:54 UTC 2022 , Edited by admin on Fri Dec 16 18:24:54 UTC 2022
PRIMARY
RS_ITEM_NUM
1605205
Created by admin on Fri Dec 16 18:24:54 UTC 2022 , Edited by admin on Fri Dec 16 18:24:54 UTC 2022
PRIMARY
ChEMBL
CHEMBL589
Created by admin on Fri Dec 16 18:24:54 UTC 2022 , Edited by admin on Fri Dec 16 18:24:54 UTC 2022
PRIMARY
MERCK INDEX
M9658
Created by admin on Fri Dec 16 18:24:54 UTC 2022 , Edited by admin on Fri Dec 16 18:24:54 UTC 2022
PRIMARY Merck Index
DAILYMED
D7ZD41RZI9
Created by admin on Fri Dec 16 18:24:54 UTC 2022 , Edited by admin on Fri Dec 16 18:24:54 UTC 2022
PRIMARY
FDA UNII
D7ZD41RZI9
Created by admin on Fri Dec 16 18:24:54 UTC 2022 , Edited by admin on Fri Dec 16 18:24:54 UTC 2022
PRIMARY
DRUG BANK
DBSALT000390
Created by admin on Fri Dec 16 18:24:54 UTC 2022 , Edited by admin on Fri Dec 16 18:24:54 UTC 2022
PRIMARY
NCI_THESAURUS
C47710
Created by admin on Fri Dec 16 18:24:54 UTC 2022 , Edited by admin on Fri Dec 16 18:24:54 UTC 2022
PRIMARY
EPA CompTox
DTXSID50238533
Created by admin on Fri Dec 16 18:24:54 UTC 2022 , Edited by admin on Fri Dec 16 18:24:54 UTC 2022
PRIMARY
RXCUI
236553
Created by admin on Fri Dec 16 18:24:54 UTC 2022 , Edited by admin on Fri Dec 16 18:24:54 UTC 2022
PRIMARY RxNorm
Related Record Type Details
BASIS OF STRENGTH->SUBSTANCE
ASSAY (HPLC)
USP
PARENT -> SALT/SOLVATE
Related Record Type Details
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
Ph.Eur.; USP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
Ph.Eur.; USP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
Ph.Eur.; USP
Related Record Type Details
ACTIVE MOIETY