Ropinirole,sold under the brand nameRequipamong others, is amedicationused to treatParkinson's disease(PD) andrestless legs syndrome(RLS).[3]It is takenby mouth.[4]
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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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| Bioavailability | 50%[2] | ||
| Metabolism | Liver(CYP1A2)[2] | ||
| Eliminationhalf-life | 5-6 hours[2] | ||
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| ECHA InfoCard | 100.110.353 | ||
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| Formula | C16H24N2O | ||
| Molar mass | 260.381g·mol−1 | ||
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Common side effects include sleepiness, vomiting, and dizziness.[4]Serious side effects may includepathological gambling,low blood pressure with standingandhallucinations.[3][4]Use inpregnancyandbreastfeedingis of unclear safety.[5]It is adopamine agonistand works by triggeringdopamine D2receptors.[4]
It was approved for medical use in the United States in 1997.[4]It is available as ageneric medication.[3]In 2022, it was the 163rd most commonly prescribed medication in the United States, with more than 3million prescriptions.[6][7]
Medical uses
editRopinirole 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 dysfunctionanderectile dysfunctioncaused by eitherSSRIs[8]or antipsychotics.
A 2008meta-analysisfound that ropinirole was less effective thanpramipexolein the treatment of restless legs syndrome.[9]
Side effects
editRopinirole can cause nausea, dizziness, hallucinations,orthostatic hypotension,and sudden sleep attacks during the daytime. Unusual side effects specific to D3agonists such as ropinirole andpramipexolecan includehypersexuality,pundingandcompulsive 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 of these drugs is often very difficult and generally should be supervised by a medical professional.[11]
Pharmacology
edit| 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,andD4dopaminereceptoragonistwith highestaffinityfor D3,which are mostly found in the limbic areas.[13]It is weakly active at the5-HT2,andα2receptors and is said to have virtually no affinity for the5-HT1,GABA,mAChRs,α1-, andβ-adrenoreceptors.[14]It is apotentagonist of the5-HT2Breceptor,but showsbiased agonismat this receptor and does not appear to pose a risk ofcardiac valvulopathy.[15][16]
Ropinirole is metabolized primarily bycytochrome P450CYP1A2to 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,CYP2D6may be inhibited, although this has been tested onlyin vitro.[2]
Society and culture
editIt is manufactured byGlaxoSmithKline(GSK),Mylan Pharmaceuticals,Cipla,Dr. Reddy's LaboratoriesandSun Pharmaceutical.The discovery of the drug's utility in restless legs syndrome has been used as an example of successfuldrug repurposing.[18]
Lawsuits
editIn November 2012,GlaxoSmithKlinewas ordered by aRennesappeals 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]
References
edit- ^Anvisa(31 March 2023)."RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial"[Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control] (in Brazilian Portuguese).Diário Oficial da União(published 4 April 2023).Archivedfrom the original on 3 August 2023.Retrieved16 August2023.
- ^abcdTompson DJ, Vearer D (December 2007). "Steady-state pharmacokinetic properties of a 24-hour prolonged-release formulation of ropinirole: results of two randomized studies in patients with Parkinson's disease".Clinical Therapeutics.29(12): 2654–2666.doi:10.1016/j.clinthera.2007.12.010.PMID18201581.
- ^abcBritish National Formulary(76th ed.). Pharmaceutical Press. 2018. pp. 419–420.ISBN978-0-85711-338-2.
- ^abcde"Ropinirole Hydrochloride Monograph for Professionals".Drugs.com.American Society of Health-System Pharmacists.Retrieved3 March2019.
- ^"Ropinirole Pregnancy and Breastfeeding Warnings".Drugs.com.Retrieved3 March2019.
- ^"The Top 300 of 2022".ClinCalc.Archivedfrom the original on 30 August 2024.Retrieved30 August2024.
- ^"Ropinirole Drug Usage Statistics, United States, 2013 - 2022".ClinCalc.Retrieved30 August2024.
- ^Clinical trial numberNCT00334048atClinicalTrials.gov- "Treating Sexual Dysfunction From SSRI Medication: a Study Comparing Requip CR to Placebo"
- ^Quilici S, Abrams KR, Nicolas A, Martin M, Petit C, Lleu PL, et al. (October 2008). "Meta-analysis of the efficacy and tolerability of pramipexole versus ropinirole in the treatment of restless legs syndrome".Sleep Med.9(7): 715–26.doi:10.1016/j.sleep.2007.11.020.PMID18226947.
- ^Bostwick JM, Hecksel KA, Stevens SR, Bower JH, Ahlskog JE (April 2009)."Frequency of new-onset pathologic compulsive gambling or hypersexuality after drug treatment of idiopathic Parkinson disease".Mayo Clinic Proceedings.84(4): 310–316.doi:10.4065/84.4.310.PMC2665974.PMID19339647.
- ^"What is Augmentation?"(PDF).Austin, Texas: Restless Legs Syndrome (RLS) Foundation. Archived fromthe original(PDF)on 9 May 2018.Retrieved8 May2018.
- ^Coldwell MC, Boyfield I, Brown T, Hagan JJ, Middlemiss DN (1999)."Comparison of the functional potencies of ropinirole and other dopamine receptor agonists at human D2(long), D3 and D4.4 receptors expressed in Chinese hamster ovary cells".British Journal of Pharmacology.127(7): 1696–1702.doi:10.1038/sj.bjp.0702673.PMC1566138.PMID10455328.
- ^Shill HA, Stacy M (2009)."Update on ropinirole in the treatment of Parkinson's disease".Neuropsychiatric Disease and Treatment.5:33–36.PMC2695212.PMID19557097.
- ^Eden RJ, Costall B, Domeney AM, Gerrard PA, Harvey CA, Kelly ME, et al. (January 1991). "Preclinical pharmacology of ropinirole (SK&F 101468-A) a novel dopamine D2 agonist".Pharmacology, Biochemistry, and Behavior.38(1): 147–154.doi:10.1016/0091-3057(91)90603-Y.PMID1673248.S2CID26842270.
- ^Bender AM, Parr LC, Livingston WB, Lindsley CW, Merryman WD (August 2023)."2B Determined: The Future of the Serotonin Receptor 2B in Drug Discovery".J Med Chem.66(16): 11027–11039.doi:10.1021/acs.jmedchem.3c01178.PMC11073569.PMID37584406.S2CID260924858.
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
- ^Huang XP, Setola V, Yadav PN, Allen JA, Rogan SC, Hanson BJ, et al. (October 2009)."Parallel functional activity profiling reveals valvulopathogens are potent 5-hydroxytryptamine(2B) receptor agonists: implications for drug safety assessment".Mol Pharmacol.76(4): 710–22.doi:10.1124/mol.109.058057.PMC2769050.PMID19570945.
- ^Tompson D, Hewens D, Earl N, Oliveira D, Taubel J, Swan S, et al. (7–11 June 2009).An open-label, parallel-group, repeat-dose study to investigate the effects of end-stage renal disease and haemodialysis on the pharmacokinetics of ropinirole](PDF).13th International Congress of Parkinson’s Disease and Movement Disorders. Paris, France. Archived fromthe original(PDF)on 17 March 2012.
- ^Lipp E (1 August 2008)."Novel Approaches to Lead Optimization".Genetic Engineering & Biotechnology News.Vol. 28, no. 14. p. 20.Retrieved28 September2008.
- ^Wong C (29 November 2012)."Court Rules Parkinson's Drug Turned Straight Patient Into A Gay Sex Addict".Huffington Post.
