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

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
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
[Dopaminergic agonists in the treatment of Parkinson's disease].	2000 Dec	11194495
Ropinirole for levodopa-induced complications in Parkinson's disease.	2001	11279718
Efficacy and tolerability of dopamine agonists in a parkinsonian population.	2001 Feb	11487183
Possible applications for dopaminergic agents following traumatic brain injury: part 2.	2001 Feb	11277855
Literature alert.	2001 Jul	11898535
Antiparkinsonian activity and dyskinesia risk of ropinirole and L-DOPA combination therapy in drug naïve MPTP-lesioned common marmosets (Callithrix jacchus).	2001 Jul	11481686
Long-duration effect and the postsynaptic compartment: study using a dopamine agonist with a short half-life.	2001 Mar	11295785
[Parkinson disease: diagnostic and therapeutic criteria].	2001 Mar 3	11268897
Sleep attacks and antiparkinsonian drugs: a pilot prospective pharmacoepidemiologic study.	2001 May-Jun	11391132
Two advances in the management of Parkinson disease.	2002 Aug	12184472
[The usefulness of dopaminergic drugs in traumatic brain injury].	2002 Aug 16-31	12235569
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
Restless legs syndrome: treatment with dopaminergic agents.	2002 Feb 26	11909990
Pergolide in the treatment of patients with early and advanced Parkinson's disease.	2002 Jan-Feb	11852289
Gateways to clinical trials.	2002 Jul-Aug	12224444
Effect of dopamine receptor agonists on sensory nerve activity: possible therapeutic targets for the treatment of asthma and COPD.	2002 Jun	12055141
Levodopa but not ropinirole induces an internalization of D1 dopamine receptors in parkinsonian rats.	2002 Nov	12465054
Practical importance of neuroprotection in Parkinson's disease.	2002 Oct	12522574
Neuroprotection in idiopathic Parkinson's disease.	2002 Oct	12522567
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	14592182
The timing of antiparkinsonian treatment reduction after subthalamic nucleus stimulation.	2003	12464720
[Sexual delinquency and Parkinson's disease].	2003 Apr	12707708
Sleep attacks, daytime sleepiness, and dopamine agonists in Parkinson's disease.	2003 Jun	12784269
Potent activation of dopamine D3/D2 heterodimers by the antiparkinsonian agents, S32504, pramipexole and ropinirole.	2003 Nov	14535946

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.

Substance Class	Chemical Created by `admin` on `Sat Dec 16 15:50:19 GMT 2023` Edited by `admin` on `Sat Dec 16 15:50:19 GMT 2023`
Record UNII	030PYR8953
Record Status	`Validated (UNII)`
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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