Rotigotine

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 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 (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, insomnia, somnolence, confusion, and hallucinations. More serious complications can include psychosis and impulse control disorders like hypersexuality, punding, and pathological gambling. Mild adverse skin reactions at the patch application site may also occur.

Pharmacology

Rotigotine acts as a non-selective agonist of the dopamine D₁, D₂, D₃, and, to a lesser extent, D₄ and D₅ receptors, 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 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 in the treatment of Parkinson's disease than D₂-like-selective agonists but has suboptimal pharmacokinetic properties) and pergolide but unlike pramipexole and ropinirole.

Rotigotine possesses the following ''in vitro'' receptor 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 materials except that for α_2B-adrenergic which was done with NG 108–15 cells. Rotigotine behaves as a partial or full agonist (depending on the assay) at all dopamine receptors listed, as an antagonist 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.

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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