General
Preferred name
ROPINIROLE
Synonyms
ROPINIROLE HYDROCHLORIDE ()
SKF 101468 hydrochloride ()
Ropinirole HCl ()
SKF-101468A ()
Ropinirole (hydrochloride) ()
ropinirole XR, GSK ()
SKF 101468 (hydrochloride) ()
Aimpart XL ()
Adartrel ()
Ropilynz XL ()
SK&F 101468-A ()
Ralnea XL ()
Requip Xl ()
Raponer XL ()
Spiroco XL ()
Repinex XL ()
Requip ()
Ipinnia XL ()
Ropinirole (as hydrochloride) ()
SK&F-101468-A ()
NSC-758917 ()
SK&F 101468 ()
Ropinirole-d7 (hydrochloride) ()
P&D ID
PD010133
CAS
91374-20-8
91374-21-9
1261396-31-9
Tags
natural product
drug
available
Approved by
PMDA
FDA
First approval
1997
Drug Status
investigational
approved
vet_approved
Drug indication
Parkinson disease
Antiparkinsonian (D2 receptor agonist)
Max Phase
Phase 4
Structure
Probe scores
P&D probe-likeness score
[[ v.score ]]%
Structure formats
[[ format ]]
[[ compound[format === 'MOL' ? 'molblock' : format.toLowerCase()] ]]
Description
(extracted from source data)
HALF-LIFE Approximately 6 hours [FDA label], [A37840].
ROE The majority of the absorbed dose is cleared by the liver [A35711]. In clinical trials, more than 88% of a radiolabeled dose was recovered in urine [FDA 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%) [FDA label].
INDICATION For the treatment of the signs and symptoms of Parkinson's disease and for the treatment of primary moderate-severe restless legs syndrome [FDA 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 [FDA label], both of which are inactive [A35711]. 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 [FDA label]. _In vitro_ studies show that the major cytochrome P450 enzyme involved in the metabolism of ropinirole is CYP1A2 [FDA label], [A37840].
ABSORPTION Ropinirole is rapidly absorbed after oral administration, reaching peak concentration in approximately 1 to 2 hours [FDA label], [A37840]. Absolute bioavailability was 45% to 55%, suggesting approximately 50% hepatic first-pass effect [FDA label]. The bioavailability of ropinirole prolonged release compared to the immediate release tablets is about 100% [A38215]. 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 [FDA label].
MOA 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 [A35711]. 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 [A35711].; ; ; 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 [FDA label].
ROE The majority of the absorbed dose is cleared by the liver [A35711].; ; In clinical trials, more than 88% of a radiolabeled dose was recovered in urine [FDA 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%) [FDA 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 [FDA 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 [FDA label].; ; **Mutagenesis**; ; Ropinirole was not found to be mutagenic or clastogenic during in vitro assays, or in the in vivo mouse micronucleus test [FDA 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 [FDA 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 [FDA label], both of which are inactive [A35711].; ; 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 [FDA label].; ; _In vitro_ studies show that the major cytochrome P450 enzyme involved in the metabolism of ropinirole is CYP1A2 [FDA label], [A37840].
DESCRIPTION Ropinirole is a dopamine agonist. This drug is active at the dopamine-D2 and -D3 receptor subtypes, both centrally and peripherally. (GtoPdb)
MOA 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 [A35711]. 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 [A35711]. 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 [FDA label].
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 [FDA 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 [FDA 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 [FDA 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 [FDA 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 [FDA 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 [FDA label]. **Mutagenesis** Ropinirole was not found to be mutagenic or clastogenic during in vitro assays, or in the in vivo mouse micronucleus test [FDA 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 [FDA label].
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 [FDA 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 [FDA 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 [FDA 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 [FDA label].
ABSORPTION Ropinirole is rapidly absorbed after oral administration, reaching peak concentration in approximately 1 to 2 hours [FDA label], [A37840].; ; Absolute bioavailability was 45% to 55%, suggesting approximately 50% hepatic first-pass effect [FDA label]. The bioavailability of ropinirole prolonged release compared to the immediate release tablets is about 100% [A38215].; ; 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 [FDA label].
DESCRIPTION Selective M1 agonist (Tocris Bioactive Compound Library)
DESCRIPTION Selective D2 dopamine receptor agonist (LOPAC library)
DESCRIPTION Ropinirole a selective D-2 agonist with Ki of 29 nM. (BOC Sciences Bioactive Compounds)
Cell lines
0
Organisms
2
Compound Sets
34
AdooQ Bioactive Compound Library
A11915
Axon Medchem Screening Library
1514
BOC Sciences Bioactive Compounds
ropinirole-hcl-cas-91374-20-8-item-84-79480
Cayman Chemical Bioactives
23871
31689
ChEMBL Approved Drugs
CHEMBL1200411
CHEMBL589
ChEMBL Drugs
CHEMBL1200411
CHEMBL589
Concise Guide to Pharmacology 2017/18
7295
Concise Guide to Pharmacology 2019/20
7295
Concise Guide to Pharmacology 2021/22
7295
Concise Guide to Pharmacology 2023/24
7295
Drug Repurposing Hub
DrugBank
DB00268
DrugBank Approved Drugs
DB00268
DrugCentral
2402
DrugCentral Approved Drugs
2402
DrugMAP
DMA6S1D
DrugMAP Approved Drugs
DMA6S1D
DrugMatrix
Enamine BioReference Compounds
EU-OPENSCREEN Bioactive Compound Library
EOS101587
Guide to Pharmacology
7295
Ki Database
Ropinirole
LOPAC library
LSP-MoA library (Laboratory of Systems Pharmacology)
CHEMBL589
MedChem Express Bioactive Compound Library
HY-B0623A
NCATS Inxight Approved Drugs
030PYR8953
NPC Screening Collection
Prestwick Chemical Library
ReFrame library
Selleckchem Bioactive Compound Library
ropinirole-hydrochloride
TargetMol Bioactive Compound Library
T2592
The Spectrum Collection
Tocris Bioactive Compound Library
3680
ZINC Tool Compounds
ZINC000000002041
External IDs
56
Properties
(calculated by RDKit )
Molecular Weight
260.19
Hydrogen Bond Acceptors
2
Hydrogen Bond Donors
1
Rotatable Bonds
7
Ring Count
2
Aromatic Ring Count
1
cLogP
2.85
TPSA
32.34
Fraction CSP3
0.56
Chiral centers
0.0
Largest ring
6.0
QED
0.82
Structural alerts
0
No structural alerts detected
Related compounds
Custom attributes
(extracted from source data)
Selectivity
D2
Pathway
GPCR/G protein
Neuroscience
Neuronal Signaling
Primary Target
Non-selective Dopamine
MOA
Agonist
Dopamine Receptor agonist
Indication
Parkinson's Disease, restless leg syndrome
Target
ADRA2A, ADRA2B, ADRA2C, DRD1, DRD2, DRD3, DRD4, DRD5, HTR1A, HTR1B, HTR1D, HTR2A, HTR2B, HTR2C
DA agonist
Dopamine Receptor
Therapeutic Class
Antiparkinson Agents
Source data