Ropinirole

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Ropinirole
Ropinirole Structural Formulae.svg Ropinirole ball-and-stick model.png
Clinical data
Trade names Requip
AHFS/Drugs.com Monograph
MedlinePlus a698013
Pregnancy
category
  • C
Routes of
administration
Oral
ATC code
Legal status
Legal status
  • In general: ℞ (Prescription only)
Pharmacokinetic data
Bioavailability 50%[1]
Metabolism Hepatic (CYP1A2)[1]
Elimination half-life 5-6 hours[1]
Identifiers
CAS Number
  • 91374-21-9 YesY
PubChem CID
  • 5095
IUPHAR/BPS
  • 7295
DrugBank
  • DB00268 YesY
ChemSpider
  • 4916 YesY
UNII
  • 030PYR8953
KEGG
  • D08489 YesY
ChEBI
  • CHEBI:8888 YesY
ChEMBL
  • CHEMBL589 YesY
ECHA InfoCard 100.110.353
Chemical and physical data
Formula C16H24N2O
Molar mass 260.375 g/mol
3D model (JSmol)
  • Interactive image
  (verify)

Ropinirole (INN; trade names Requip, Repreve, Ronirol, Adartrel) is a dopamine agonist of the non-ergoline class of medications. It is manufactured by GlaxoSmithKline (GSK), Cipla, Dr. Reddy's Laboratories and Sun Pharmaceutical. It is used in the treatment of Parkinson's disease and restless legs syndrome (RLS). Ropinirole is one of three medications approved by the FDA to treat RLS, the other two being pramipexole (Mirapex) and gabapentin enacarbil (Horizant). The discovery of the drug's utility in RLS has been used as an example of successful drug repurposing.[2]

Ropinirole's patent expired in May 2008, and the drug is now available in generic form.[3]

Medical uses

Ropinirole is prescribed for mainly Parkinson's disease, RLS and extrapyramidal symptoms. It can also reduce the side effects caused by selective serotonin reuptake inhibitors, including Parkinsonism syndrome as well as sexual dysfunction and erectile dysfunction caused by either SSRIs[4] or antipsychotics.

Dosage

Ropinirole in the Requip form is available in various preparations, ranging from a 0.25 mg tablet to a 5 mg tablet. The primary reason is dose titration. This implies that the person taking Requip has to closely interact and communicate with the primary care physician with regard to how much should actually be taken by the patient.

For Parkinson's disease, the maximum recommended dose is 24 mg per day, taken in three separate doses spread throughout the day. The maximum dose recommendations of ropinirole for subjects with end stage renal disease (ESRD) should be reduced by 25% compared with those recommended for subjects with normal renal function. A 25% dose reduction represents a more straightforward dosage regimen in terms of available tablet strength, compared with a 30% dose reduction.[5]

For RLS, the maximum recommended dose is 4 mg per day, taken 1 to 3 hours before bedtime. A 52-week open label study had a mean dosage of 1.90 mg, once daily 1 to 3 hours before bedtime.[6]

Pharmacology

Ropinirole acts as a D2, D3, and D4 dopamine receptor agonist with highest affinity for D2. It is weakly active at the 5-HT2, and α2 receptors and is said to have virtually no affinity for the 5-HT1, GABA, mAChRs, α1, and β-adrenoreceptors.[7]

Ropinirole is metabolized primarily by cytochrome P450 CYP1A2 to form two metabolites; SK&F-104557 and SK&F-89124, both of which are renally excreted,[5] and at doses higher than clinical, is also metabolized by CYP3A4. At doses greater than 24 mg, CYP2D6 may be inhibited, although this has only been tested in vitro.[1]

Side effects

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 behaviours.[8]

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 RLS 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. [9]

Lawsuits

In November 2012, GlaxoSmithKline was ordered by a Rennes 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 Parkinson's treatment.[10]

See also

References

  1. ^ a b c d Tompson, Debra J.; et al. (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 Pharmacokinetics. 29 (12): 2654–66. doi:10.1016/j.clinthera.2007.12.010. PMID 18201581. 
  2. ^ Lipp, Elizabeth (2008-08-01). "Novel Approaches to Lead Optimization". Genetic Engineering & Biotechnology News. Drug Discovery. 28 (14). Mary Ann Liebert. p. 20. ISSN 1935-472X. Retrieved 2008-09-28.  Note: The opinion that ropinirole's use in RLS was a successful example of drug repurposes was reported as being that of Josef Scheiber, a post-doctoral fellow at the Novartis Institutes for BioMedical Research.
  3. ^ New pharmaceutical products: Ceftriaxon-Rocephin, Granisetron-Kytril, Ipratropium-Albuterol
  4. ^ Clinical trial number NCT00334048 at ClinicalTrials.gov - "Treating Sexual Dysfunction From SSRI Medication: a Study Comparing Requip CR to Placebo"
  5. ^ a b An open-label, parallel-group, repeat-dose study to investigate the effects of end-stage renal disease and haemodialysis on the pharmacokinetics of ropinirole | Authors: Debra J. Tompson, Deborah Hewens, Nancy Earl, David Oliveira, Jorg Taubel, Suzanne Swan, Luigi Giorgi | 13th International Congress of Parkinson’s Disease and Movement Disorders, Paris, France, June 7–11, 2009
  6. ^ Garcia-Borreguero D, Grunstein R, Sridhar G, et al. (November 2007). "A 52-week open-label study of the long-term safety of ropinirole in patients with restless leg syndrome". Sleep Med. 8 (7–8): 742–52. doi:10.1016/j.sleep.2006.09.009. PMID 17512789. 
  7. ^ Eden, R. J.; et al. (1991). "Preclinical Pharmacology of Ropinirole (SK&F 101468-A) a Novel Dopamine D 2 Agonist". Pharmacology Biochemistry and Behavior. 38: 147–154. doi:10.1016/0091-3057(91)90603-Y. 
  8. ^ Bostwick JM, Hecksel KA, Stevens SR, Bower JH, Ahlskog JE (2009). "Frequency of new-onset pathologic compulsive gambling or hypersexuality after drug treatment of idiopathic Parkinson disease". Mayo Clinic Proceedings. 84 (4): 310–6. doi:10.4065/84.4.310. PMC 2665974Freely accessible. PMID 19339647. 
  9. ^ https://www.rls.org/file/what-is-augmentation.pdf
  10. ^ Wong, Curtis (2012-11-29). "Court Rules Parkinson's Drug Turned Straight Patient Into A Gay Sex Addict". Huffington Post. 

External links

  • Requip for RLS
  • Requip for PD
  • Requip - Clinical Pharmacology
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