rotigotine

General side effects for rotigotine may include constipation, dyskinesia, nausea, vomiting, dizziness, fatigue, insomnia, somnolence, confusion, and hallucinations.{{cite journal | vauthors = Kulisevsky J, Pagonabarraga J | title = Tolerability and safety of ropinirole versus other dopamine agonists and levodopa in the treatment of Parkinson's disease: meta-analysis of randomized controlled trials | journal = Drug Safety | volume = 33 | issue = 2 | pages = 147–161 | date = February 2010 | pmid = 20082541 | doi = 10.2165/11319860-000000000-00000 | s2cid = 34876593 }}{{cite journal | author = Parkinson Study Group | title = A controlled trial of rotigotine monotherapy in early Parkinson's disease | journal = Archives of Neurology | volume = 60 | issue = 12 | pages = 1721–1728 | date = December 2003 | pmid = 14676046 | doi = 10.1001/archneur.60.12.1721 | doi-access = free }} More serious complications can include psychosis and impulse-control disorders like hypersexuality, punding, and pathological gambling.{{cite journal | vauthors = Wingo TS, Evatt M, Scott B, Freeman A, Stacy M | title = Impulse control disorders arising in 3 patients treated with rotigotine | journal = Clinical Neuropharmacology | volume = 32 | issue = 2 | pages = 59–62 | year = 2009 | pmid = 18978496 | doi = 10.1097/WNF.0B013E3181684542 | s2cid = 23942499 }} Mild adverse skin reactions at the patch application site may also occur.

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.{{cite journal | vauthors = Wood M, Dubois V, Scheller D, Gillard M | title = Rotigotine is a potent agonist at dopamine D1 receptors as well as at dopamine D2 and D3 receptors | journal = British Journal of Pharmacology | volume = 172 | issue = 4 | pages = 1124–1135 | date = February 2015 | pmid = 25339241 | pmc = 4314200 | doi = 10.1111/bph.12988 }} 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 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.

File:7x2c Rotigotine D2 protein-ligand.png

Initially developed at the University of Groningen in 1985 as N-0437,{{cite journal |vauthors=Horn AS, Tepper P, Van der Weide J, Watanabe M, Grigoriadis D, Seeman P |date=October 1985 |title=Synthesis and radioreceptor binding activity of N-0437, a new, extremely potent and selective D2 dopamine receptor agonist |journal=Pharmaceutisch Weekblad. Scientific Edition |volume=7 |issue=5 |pages=208–211 |doi=10.1007/bf02307578 |pmid=2933633 |s2cid=8847550}} Aderis Pharmaceuticals acquired rotigotine and continued development toward commercialization.{{cn|date=April 2022}} In 1998, Aderis globally out-licensed rotigotine for development and commercialization to Schwarz Pharma,Development & Commercialization of rotigotine by Aderis ([http://www.aderis.com/products/rotigotine.htm Aderis Pharmaceuticals making a reference for the commercialization of rotigotine]) which firm was acquired by UCB S.A. in 2006. Schwarz completed acquisition of full rights to rotigotine from Aderis as of 2005.{{Cite web |title=SCHWARZ PHARMA ACQUIRES REMAINING RIGHTS TO ROTIGOTINE FROM ADERIS {{!}} FDAnews |url=https://www.fdanews.com/articles/74339-schwarz-pharma-acquires-remaining-rights-to-rotigotine-from-aderis |access-date=11 August 2022 |website=www.fdanews.com}}

The drug was approved by the European Medicines Agency (EMA) for use in Europe in 2006.{{cite web |date=17 September 2018 |title=Neupro EPAR |url=https://www.ema.europa.eu/en/medicines/human/EPAR/neupro |access-date=2 March 2020 |website=European Medicines Agency}} In 2007, the Neupro patch was approved by the US Food and Drug Administration (FDA).{{Cite web |last=PubChem |title=Rotigotine |url=https://pubchem.ncbi.nlm.nih.gov/compound/59227 |access-date=11 August 2022 |website=pubchem.ncbi.nlm.nih.gov}} It became the first transdermal treatment of Parkinson's disease in the United States.{{Citation needed|date=August 2022}} 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.{{cite journal |vauthors=Zhou CQ, Li SS, Chen ZM, Li FQ, Lei P, Peng GG |date=23 July 2013 |title=Rotigotine transdermal patch in Parkinson's disease: a systematic review and meta-analysis |journal=PLOS ONE |volume=8 |issue=7 |pages=e69738 |bibcode=2013PLoSO...869738Z |doi=10.1371/journal.pone.0069738 |pmc=3720658 |pmid=23936090 |doi-access=free}} The patch was reformulated, and was reintroduced in the United States in 2012.{{Cite web |title=Neupro Patch Re-launches in the US |url=http://www.pdf.org/en/media_pr/release/pr_1342559027 |url-status=dead |archive-url=https://web.archive.org/web/20160323100931/http://www.pdf.org/en/media_pr/release/pr_1342559027 |archive-date=23 March 2016 |access-date=12 September 2012}}

Rotigotine was authorized as a treatment for restless legs syndrome in the European Union in August 2008.

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Category:5-HT1A agonists

Category:Adrenergic receptor modulators

Category:Alpha-2 blockers

Category:Aminotetralins

Category:D1 receptor agonists

Category:D2 receptor agonists

Category:D3 receptor agonists

Category:D4 receptor agonists

Category:D5 receptor agonists

Category:Dipropylamino compounds

Category:Hydroxyarenes

Category:Thiophenes

Category:Parkinson's disease