Ropinirole, sold under the brand name Requip among others, is a medication used to treat
Parkinson's disease
Parkinson's disease (PD), or simply Parkinson's, is a long-term degenerative disorder of the central nervous system that mainly affects the motor system. The symptoms usually emerge slowly, and as the disease worsens, non-motor symptoms beco ...
(PD) and
restless legs syndrome (RLS).
In PD the dose needs to be adjusted to the effect and treatment should not be suddenly stopped.
[ It is taken by mouth.][
Common side effects include sleepiness, vomiting, and dizziness.][ Serious side effects may include ]pathological gambling
Problem gambling or ludomania is repetitive gambling behavior despite harm and negative consequences. Problem gambling may be diagnosed as a mental disorder according to ''DSM-5'' if certain diagnostic criteria are met. Pathological gambling is ...
, low blood pressure with standing and hallucinations
A hallucination is a perception in the absence of an external stimulus that has the qualities of a real perception. Hallucinations are vivid, substantial, and are perceived to be located in external objective space. Hallucination is a combinati ...
.[ Use in ]pregnancy
Pregnancy is the time during which one or more offspring develops ( gestates) inside a woman's uterus (womb). A multiple pregnancy involves more than one offspring, such as with twins.
Pregnancy usually occurs by sexual intercourse, but ...
and breastfeeding
Breastfeeding, or nursing, is the process by which human breast milk is fed to a child. Breast milk may be from the breast, or may be expressed by hand or pumped and fed to the infant. The World Health Organization (WHO) recommends that bre ...
is of unclear safety. It is a dopamine agonist and works by triggering dopamine D2 receptors.
It was approved for medical use in the United States in 1997.[ It is available as a ]generic medication
A generic drug is a pharmaceutical drug that contains the same chemical substance as a drug that was originally protected by chemical patents. Generic drugs are allowed for sale after the patents on the original drugs expire. Because the active ...
.[ In 2020, it was the 156th most commonly prescribed medication in the United States, with more than 3million prescriptions.
]
Medical uses
Ropinirole is prescribed for mainly Parkinson's disease
Parkinson's disease (PD), or simply Parkinson's, is a long-term degenerative disorder of the central nervous system that mainly affects the motor system. The symptoms usually emerge slowly, and as the disease worsens, non-motor symptoms beco ...
, 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
Erectile dysfunction (ED), also called impotence, is the type of sexual dysfunction in which the penis fails to become or stay erect during sexual activity. It is the most common sexual problem in men.Cunningham GR, Rosen RC. Overview of ma ...
caused by either SSRIs or antipsychotics.
Dosage
Ropinirole is available in various preparations, ranging from a 0.25 mg tablet to a 5 mg tablet. The primary reason is dose titration.
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.
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.
Side effects
Ropinirole can cause nausea, dizziness, hallucinations, orthostatic hypotension
Orthostatic hypotension, also known as postural hypotension, is a medical condition wherein a person's blood pressure drops when standing up or sitting down. Primary orthostatic hypertension is also often referred to as neurogenic orthostatic hyp ...
, and sudden sleep attacks during the daytime. Unusual side effects specific to D3 agonists such as ropinirole and pramipexole can include hypersexuality, punding
Punding is compulsive performance of repetitive, mechanical tasks, such as assembling and disassembling, collecting, or sorting household objects. The term was originally coined to describe complex prolonged, purposeless, and stereotyped behaviou ...
and compulsive gambling
Problem gambling or ludomania is repetitive gambling behavior despite harm and negative consequences. Problem gambling may be diagnosed as a mental disorder according to ''DSM-5'' if certain diagnostic criteria are met. Pathological gambling is ...
, even in patients without a history of these behaviours.
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.
Pharmacology
Ropinirole acts as a D2, D3, and D4 dopamine
Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic chemical of the catecholamine and phenethylamine families. Dopamine constitutes about 80% o ...
receptor
Receptor may refer to:
*Sensory receptor, in physiology, any structure which, on receiving environmental stimuli, produces an informative nerve impulse
*Receptor (biochemistry), in biochemistry, a protein molecule that receives and responds to a n ...
agonist
An agonist is a chemical that activates a receptor to produce a biological response. Receptors are cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an antagonist blocks the action of the ag ...
with highest affinity for D3, which are mostly found in the limbic areas. 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.
Ropinirole is metabolized primarily by cytochrome P450
Cytochromes P450 (CYPs) are a superfamily of enzymes containing heme as a cofactor that functions as monooxygenases. In mammals, these proteins oxidize steroids, fatty acids, and xenobiotics, and are important for the clearance of various co ...
CYP1A2 to form two metabolites; SK&F-104557 and SK&F-89124, both of which are renally excreted,[An open-label, parallel-group, repeat-dose study to investigate the effects of end-stage renal disease and haemodialysis on the pharmacokinetics of ropinirole](_blank)
, 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, 7–11 June 2009 and at doses higher than clinical, is also metabolized by CYP3A4
Cytochrome P450 3A4 (abbreviated CYP3A4) () is an important enzyme in the body, mainly found in the liver and in the intestine. It oxidizes small foreign organic molecules ( xenobiotics), such as toxins or drugs, so that they can be removed from ...
. At doses greater than 24 mg, CYP2D6 may be inhibited, although this has been tested only in vitro
''In vitro'' (meaning in glass, or ''in the glass'') studies are performed with microorganisms, cells, or biological molecules outside their normal biological context. Colloquially called " test-tube experiments", these studies in biology a ...
.[
]
Society and culture
It is manufactured by GlaxoSmithKline
GSK plc, formerly GlaxoSmithKline plc, is a British multinational pharmaceutical and biotechnology company with global headquarters in London, England. Established in 2000 by a merger of Glaxo Wellcome and SmithKline Beecham. GSK is the tent ...
(GSK), Mylan Pharmaceuticals
Mylan N.V. was a global generic and specialty pharmaceuticals company. In November 2020, Mylan merged with Upjohn, Pfizer's off-patent medicine division, to form Viatris. Previously, the company was domiciled in the Netherlands, with principal ...
, Cipla, Dr. Reddy's Laboratories and Sun Pharmaceutical. The discovery of the drug's utility in RLS has been used as an example of successful drug repurposing
Drug repositioning (also called drug repurposing) involves the investigation of existing drugs for new therapeutic purposes.
Repurposing achievements
A number of successes have been achieved, the foremost including sildenafil (Viagra) for erect ...
.[ ''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.'']
Lawsuits
In November 2012, GlaxoSmithKline
GSK plc, formerly GlaxoSmithKline plc, is a British multinational pharmaceutical and biotechnology company with global headquarters in London, England. Established in 2000 by a merger of Glaxo Wellcome and SmithKline Beecham. GSK is the tent ...
was ordered by a Rennes
Rennes (; br, Roazhon ; Gallo: ''Resnn''; ) is a city in the east of Brittany in northwestern France at the confluence of the Ille and the Vilaine. Rennes is the prefecture of the region of Brittany, as well as the Ille-et-Vilaine departme ...
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.
References
External links
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