Rotigotine, sold under the brand name Neupro among others, is a

dopamine agonist A dopamine agonist (DA) is a compound that activates dopamine receptors. There are two families of dopamine receptors, D2-like and D1-like, and they are all G protein-coupled receptors. D1- and D5-receptors belong to the D1-like family and the ...

of the non-

ergoline Ergoline is a chemical compound whose structural skeleton is contained in a variety of alkaloids, referred to as ergoline derivatives or ergoline alkaloids. Ergoline alkaloids, one being ergine, were initially characterized in ergot. Some of thes ...

class of medications indicated for the treatment of

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 ...

and

restless legs syndrome Restless legs syndrome (RLS), also known as Willis-Ekbom disease (WED), is generally a long-term disorder that causes a strong urge to move one's legs. There is often an unpleasant feeling in the legs that improves somewhat by moving them. This ...

. It is formulated as a once-daily

transdermal patch A transdermal patch is a medicated adhesive patch that is placed on the skin to deliver a specific dose of medication through the skin and into the bloodstream. An advantage of a transdermal drug delivery route over other types of medica ...

which provides a slow and constant supply of the drug over the course of 24 hours. Like other dopamine agonists, rotigotine has been shown to possess

antidepressant Antidepressants are a class of medication used to treat major depressive disorder, anxiety disorders, chronic pain conditions, and to help manage addictions. Common Side effect, side-effects of antidepressants include Xerostomia, dry mouth, weig ...

effects and may be useful in the treatment of depression as well.

History

Initially developed at the

University of Groningen The University of Groningen (abbreviated as UG; nl, Rijksuniversiteit Groningen, abbreviated as RUG) is a public research university of more than 30,000 students in the city of Groningen in the Netherlands. Founded in 1614, the university is th ...

in 1985 as N-0437, Aderis Pharmaceuticals acquired rotigotine and continued development toward commercialization. In 1998, Aderis globally out-licensed rotigotine for development and commercialization to Schwarz Pharma, which firm was acquired by UCB S.A. in 2006. Schwarz completed acquisition of full rights to rotigotine from Aderis as of 2005. The drug was approved by the

European Medicines Agency The European Medicines Agency (EMA) is an agency of the European Union (EU) in charge of the evaluation and supervision of medicinal products. Prior to 2004, it was known as the European Agency for the Evaluation of Medicinal Products or Eur ...

(EMA) for use in Europe in 2006. In 2007, the Neupro patch was approved by the

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...

(FDA). It became the first transdermal treatment of Parkinson's disease in the United States. In 2008, Schwarz Pharma recalled all Neupro patches in the United States and some in Europe because of problems with the delivery mechanism. FDA also suspended its marketing authorization after crystal formation was noted in some patches. The patch was reformulated, and was reintroduced in the United States in 2012. Rotigotine was authorized as a treatment for restless legs syndrome in August 2008.

Side effects

General

side effect In medicine, a side effect is an effect, whether therapeutic or adverse, that is secondary to the one intended; although the term is predominantly employed to describe adverse effects, it can also apply to beneficial, but unintended, consequence ...

s for rotigotine may include

constipation Constipation is a bowel dysfunction that makes bowel movements infrequent or hard to pass. The stool is often hard and dry. Other symptoms may include abdominal pain, bloating, and feeling as if one has not completely passed the bowel moveme ...

dyskinesia Dyskinesia refers to a category of movement disorders that are characterized by involuntary muscle movements, including movements similar to tics or chorea and diminished voluntary movements. Dyskinesia can be anything from a slight tremor of ...

nausea Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. While not painful, it can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of th ...

vomiting Vomiting (also known as emesis and throwing up) is the involuntary, forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose. Vomiting can be the result of ailments like food poisoning, gastroenter ...

dizziness Dizziness is an imprecise term that can refer to a sense of disorientation in space, vertigo, or lightheadedness. It can also refer to disequilibrium or a non-specific feeling, such as giddiness or foolishness. Dizziness is a common medical c ...

fatigue Fatigue describes a state of tiredness that does not resolve with rest or sleep. In general usage, fatigue is synonymous with extreme tiredness or exhaustion that normally follows prolonged physical or mental activity. When it does not resolve ...

insomnia Insomnia, also known as sleeplessness, is a sleep disorder in which people have trouble sleeping. They may have difficulty falling asleep, or staying asleep as long as desired. Insomnia is typically followed by daytime sleepiness, low energy, ...

somnolence Somnolence (alternatively sleepiness or drowsiness) is a state of strong desire for sleep, or sleeping for unusually long periods (compare hypersomnia). It has distinct meanings and causes. It can refer to the usual state preceding falling asleep ...

confusion In medicine, confusion is the quality or state of being bewildered or unclear. The term "acute mental confusion"

, and

hallucination 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 ...

s. More serious complications can include

psychosis Psychosis is a condition of the mind that results in difficulties determining what is real and what is not real. Symptoms may include delusions and hallucinations, among other features. Additional symptoms are incoherent speech and behavi ...

and

impulse control disorder Impulse-control disorder (ICD) is a class of psychiatric disorders characterized by impulsivity – failure to resist a temptation, an urge, or an impulse; or having the inability to not speak on a thought. Many psychiatric disorders feature impu ...

s like

hypersexuality Hypersexuality is extremely frequent or suddenly increased libido. It is controversial whether it should be included as a clinical diagnosis used by mental healthcare professionals. Nymphomania and satyriasis were terms previously used for the c ...

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

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 ...

. Mild adverse skin reactions at the patch application site may also occur.

Pharmacology

Rotigotine acts as a non-selective

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 ...

of the

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 ...

D₁, D₂, D₃, and, to a lesser extent, D₄ and D₅

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 ...

s, with highest affinity for the D₃ receptor. In terms of affinity, rotigotine has 10-fold selectivity for the D₃ receptor over the D₂, D₄, and D₅ receptors and 100-fold selectivity for the D₃ receptor over the D₁ receptor. In functional studies however, rotigotine behaves as a

full 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 a ...

of D₁, D₂, and D₃ with similar potencies ( EC₅₀). Its ability to activate both D₁-like and D₂-like receptors is similar to the case of apomorphine (which notably has greater

efficacy Efficacy is the ability to perform a task to a satisfactory or expected degree. The word comes from the same roots as ''effectiveness'', and it has often been used synonymously, although in pharmacology a distinction is now often made between ...

in the treatment of Parkinson's disease than D₂-like-selective agonists but has suboptimal

pharmacokinetic Pharmacokinetics (from Ancient Greek ''pharmakon'' "drug" and ''kinetikos'' "moving, putting in motion"; see chemical kinetics), sometimes abbreviated as PK, is a branch of pharmacology dedicated to determining the fate of substances administered ...

properties) and

pergolide Pergolide, sold under the brand name Permax and Prascend (veterinary) among others, is an ergoline-based dopamine receptor agonist used in some countries for the treatment of Parkinson's disease. Parkinson's disease is associated with reduced do ...

but unlike pramipexole and

ropinirole Ropinirole, sold under the brand name Requip among others, is a medication used to treat Parkinson's disease (PD) and restless legs syndrome (RLS). In PD the dose needs to be adjusted to the effect and treatment should not be suddenly stopped. ...

. Rotigotine possesses the following ''

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 ...

binding profile: * D₁ receptor (K_i = 83 nM) * D₂ receptor (K_i = 13.5 nM) * D₃ receptor (K_i = 0.71 nM) * D_4.2 receptor (K_i = 3.9 nM) * D_4.4 receptor (K_i = 15 nM) * D_4.7 receptor (K_i = 5.9 nM) * D₅ receptor (K_i = 5.4 nM) * α_1A-adrenergic receptor (K_i = 176 nM) * α_1B-adrenergic receptor (K_i = 273 nM) * α_2A-adrenergic receptor (K_i = 338 nM) * α_2B-adrenergic receptor (K_i = 27 nM) * α_2C-adrenergic receptor (K_i = 135 nM) * 5-HT_1A receptor (K_i = 30 nM) * 5-HT₇ receptor (K_i = 86 nM) * H₁ receptor (K_i = 330 nM) All affinities listed were assayed using

human Humans (''Homo sapiens'') are the most abundant and widespread species of primate, characterized by bipedalism and exceptional cognitive skills due to a large and complex brain. This has enabled the development of advanced tools, cultu ...

materials except that for α_2B-adrenergic which was done with NG 108–15 cells. Rotigotine behaves as a

partial Partial may refer to: Mathematics *Partial derivative, derivative with respect to one of several variables of a function, with the other variables held constant ** ∂, a symbol that can denote a partial derivative, sometimes pronounced "partial d ...

(depending on the assay) at all dopamine receptors listed, as an

antagonist An antagonist is a character in a story who is presented as the chief foe of the protagonist. Etymology The English word antagonist comes from the Greek ἀνταγωνιστής – ''antagonistēs'', "opponent, competitor, villain, enemy, ri ...

at the α_2B-adrenergic receptor, and as a partial agonist at the 5-HT_1A receptor. Though it has affinity for a large number of sites as shown above, at clinical doses rotigotine behaves mostly as a selective D₁-like (D₁, D₅) and D₂-like (D₂, D₃, D₄) receptor agonist, with its α_2B-adrenergic and 5-HT_1A activity also possibly having some minor relevance.

References

External links

*
Rotigotine (SPM-962) - The First Once-a-Day Transdermal Patch to Treat Parkinson's Disease
{{Portal bar , Medicine 5-HT1A agonists Adrenergic receptor modulators Alpha-2 blockers Aminotetralins D1-receptor agonists D2-receptor agonists D3 receptor agonists D4 receptor agonists D5 receptor agonists Phenols Thiophenes

History

Side effects

Pharmacology

See also

References

External links