Rotigotine

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.

All affinities listed were assayed using human materials except that for α2B-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 α2B-adrenergic receptor, and as a partial agonist at the 5-HT1A 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 α2B-adrenergic and 5-HT1A activity also possibly having some minor relevance.

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 US 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 the European Union in August 2008.

References

References

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6. Parkinson Study Group. (December 2003). "A controlled trial of rotigotine monotherapy in early Parkinson's disease". Archives of Neurology.
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8. (February 2015). "Rotigotine is a potent agonist at dopamine D1 receptors as well as at dopamine D2 and D3 receptors". British Journal of Pharmacology.
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10. (October 1985). "Synthesis and radioreceptor binding activity of N-0437, a new, extremely potent and selective D2 dopamine receptor agonist". Pharmaceutisch Weekblad. Scientific Edition.
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15. (23 July 2013). "Rotigotine transdermal patch in Parkinson's disease: a systematic review and meta-analysis". PLOS ONE.
16. "Neupro Patch Re-launches in the US".