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| Clinical data | |
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| Trade names | Requip, Repreve, Ronirol, others |
| AHFS/Drugs.com | Monograph |
| MedlinePlus | a698013 |
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| Routes of administration | By mouth |
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| Pharmacokinetic data | |
| Bioavailability | 50%[2] |
| Metabolism | Liver (CYP1A2)[2] |
| Eliminationhalf-life | 5-6 hours[2] |
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| CompTox Dashboard(EPA) | |
| ECHA InfoCard | 100.110.353 |
| Chemical and physical data | |
| Formula | C16H24N2O |
| Molar mass | 260.381 g·mol−1 |
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Ropinirole, sold under the brand nameRequip among others, is amedication used to treatParkinson's disease (PD) andrestless legs syndrome (RLS).[3] It is takenby mouth.[4]
Common side effects include sleepiness, vomiting, and dizziness.[4] Serious side effects may includepathological gambling,hypersexuality,low blood pressure with standing andhallucinations.[3][4] Use inpregnancy andbreastfeeding is of unclear safety.[5] It is adopamine agonist and works by triggeringdopamine D2 receptors.[4]
It was approved for medical use in the United States in 1997.[4] It is available as ageneric medication.[3] In 2023, it was the 212th most commonly prescribed medication in the United States, with more than 2 million prescriptions.[6][7]
Ropinirole is prescribed for mainlyParkinson's disease, restless legs syndrome, andextrapyramidal symptoms. It can also reduce the side effects caused by selective serotonin reuptake inhibitors, including Parkinsonism syndrome as well assexual dysfunction anderectile dysfunction caused by eitherSSRIs[8] or antipsychotics.
A 2008meta-analysis found that ropinirole was less effective thanpramipexole in the treatment of restless legs syndrome.[9]
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 andpramipexole can includehypersexuality,punding andcompulsive gambling, even in patients without a history of these behaviours.[10]
Ropinirole is also known to cause an effect known as "augmentation" when used to treat restless legs syndrome, where over time treatment with dopamine agonists will cause restless legs syndrome symptoms to become more severe. This usually leads to constant dosage increases in an attempt to offset the symptom progression. Symptoms will return to the level of severity they were experienced at before treatment was initiated if the drug is stopped; however, both ropinirole and pramipexole are known to cause painful withdrawal effects when treatment is stopped and the process of taking a patient who has been using the medication long-term off these drugs is often very difficult and should be supervised by a medical professional.[11]
| Target | Ki (nM) | IA% | Action |
|---|---|---|---|
| D1 | >10,000 | ? | Agonist |
| D2 | 3.7 | 100% | Full Agonist |
| D3 | 2.9 | 97% | Full Agonist |
| D4 | 7.8 | 81% | Partial Agonist |
| D5 | >10,000 | ? | Agonist |
Ropinirole acts as aD2,D3, andD4dopaminereceptoragonist with highestaffinity for D3, which are mostly found in the limbic areas.[13] It is weakly active at the5-HT2, andα2 receptors and is said to have virtually no affinity for the5-HT1,GABA,mAChRs,α1-, andβ-adrenoreceptors.[14] It is apotent agonist of the5-HT2B receptor, but showsbiased agonism at this receptor and does not appear to pose a risk ofcardiac valvulopathy.[15][16]
Ropinirole is metabolized primarily bycytochrome P450CYP1A2 to form twometabolites; SK&F-104557 and SK&F-89124, both of which are renally excreted,[17] and at doses higher than clinical, is also metabolized byCYP3A4. At doses greater than 24 mg,CYP2D6 may be inhibited, although this has been tested onlyin vitro.[2]
It is manufactured byGlaxoSmithKline (GSK),Mylan Pharmaceuticals,Cipla,Dr. Reddy's Laboratories andSun Pharmaceutical. The discovery of the drug's utility in restless legs syndrome has been used as an example of successfuldrug repurposing.[18]
In November 2012,GlaxoSmithKline was ordered by aRennes appeals court to pay Frenchman Didier Jambart 197,000 euros ($255,824); Jambart had taken ropinirole from 2003 to 2010 and exhibited risky hypersexual behavior and gambled excessively until stopping the medication.[19] This behavior displayed is characteristic ofDopamine Dysregulation Syndrome.[20]
Functionally Biased Agonists. Conversely, a compound presenting as an agonist in 5-HT2B functional assays does not necessarily pose a risk for valvulopathy. In 5-HT2B calcium flux assays, certain known VHD-associated compounds displayed an agonist profile comparable to that of ropinirole, an approved treatment for Parkinson's disease (PD) and restless leg syndrome.122 Because ropinirole is not known to be associated with VHD or similar cardiopathies, it is thought that calcium flux may not be the optimal assay for screening 5-HT2B agonists for potential VHD-related risks. In additional readouts of 5-HT2B receptor activation (calcium-sensitive NFAT-mediated transcription of a β-lactamase reporter gene, accumulation of InsPs in LiCl-treated cells, recruitment of β-arrestin to agonist-occupied receptors, and phosphorylation of the extracellular signal-regulated kinase ERK2), ropinirole was found to be "distinct from the seven known valvulopathic 5- HT2B receptor agonists [studied] in that it is much less potent, albeit not less efficacious, than the VHD-associated drugs in all but one of the 5-HT2B receptor functional assays employed." 66
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