Rotigotine, sold under the brand name Neupro among others, is a
dopamine agonist of the non-
ergoline class of medications indicated for the treatment of
Parkinson's disease and
restless legs syndrome.
It is formulated as a once-daily
transdermal patch 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-effects of antidepressants include dry mouth, weight gain, dizziness, hea ...
effects and may be useful in the treatment of
depression as well.
History
Initially developed at the
University of Groningen 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 Euro ...
(EMA) for use in Europe in 2006. In 2007, the Neupro patch was approved by the
Food and Drug Administration (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 effects for rotigotine may include
constipation,
dyskinesia,
nausea,
vomiting,
dizziness,
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,
somnolence,
confusion, and
hallucinations.
More serious complications can include
psychosis 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 imp ...
s like
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
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 ago ...
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 compound, organic chemical of the catecholamine and phenethylamine families. Dopamine const ...
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 ...
s, with highest
affinity
Affinity may refer to:
Commerce, finance and law
* Affinity (law), kinship by marriage
* Affinity analysis, a market research and business management technique
* Affinity Credit Union, a Saskatchewan-based credit union
* Affinity Equity Partn ...
for the D
3 receptor.
In terms of
affinity
Affinity may refer to:
Commerce, finance and law
* Affinity (law), kinship by marriage
* Affinity analysis, a market research and business management technique
* Affinity Credit Union, a Saskatchewan-based credit union
* Affinity Equity Partn ...
, rotigotine has 10-fold selectivity for the D
3 receptor over the D
2, D
4, and D
5 receptors and 100-fold selectivity for the D
3 receptor over the D
1 receptor.
In functional studies however, rotigotine behaves as a
full agonist of D
1, D
2, and D
3 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 pragmatic clinical trial#Efficacy versu ...
in the treatment of Parkinson's disease than D
2-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 but unlike
pramipexole and
ropinirole.
Rotigotine possesses the following ''
in vitro''
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 ...
binding profile:
*
D1 receptor (K
i = 83 nM)
*
D2 receptor (K
i = 13.5 nM)
*
D3 receptor (K
i = 0.71 nM)
*
D4.2 receptor (K
i = 3.9 nM)
*
D4.4 receptor (K
i = 15 nM)
*
D4.7 receptor (K
i = 5.9 nM)
*
D5 receptor (K
i = 5.4 nM)
*
α1A-adrenergic receptor (K
i = 176 nM)
*
α1B-adrenergic receptor (K
i = 273 nM)
*
α2A-adrenergic receptor (K
i = 338 nM)
*
α2B-adrenergic receptor (K
i = 27 nM)
*
α2C-adrenergic receptor (K
i = 135 nM)
*
5-HT1A 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 materials except that for α
2B-adrenergic which was done with
NG 108–15
Ng, ng, or NG may refer to:
* Ng (name) (黄 伍 吳), a surname of Chinese origin
Arts and entertainment
* N-Gage (disambiguation), a handheld gaming system
* Naked Giants, Seattle rock band
* '' Spirit Hunter: NG'', a video game
Businesses ...
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 ...
or
full agonist (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, riv ...
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 D
1-like (D
1, D
5) and D
2-like (D
2, D
3, D
4) receptor agonist, with its α
2B-adrenergic and 5-HT
1A activity also possibly having some minor relevance.
See also
*
Piribedil
*
Pramipexole
*
Ropinirole
References
External links
*
Rotigotine (SPM-962) - The First Once-a-Day Transdermal Patch to Treat Parkinson's Disease
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