Initially developed at the University of Groningen in 1985 as N-0437,[6] Aderis Pharmaceuticals acquired rotigotine and continued development toward commercialization.[citation needed] In 1998, Aderis globally out-licensed rotigotine for development and commercialization to Schwarz Pharma,[7] which firm was acquired by UCB S.A. in 2006. Schwarz completed acquisition of full rights to rotigotine from Aderis as of 2005.[8]
The drug was approved by the European Medicines Agency (EMA) for use in Europe in 2006.[2] In 2007, the Neupro patch was approved by the Food and Drug Administration (FDA).[9] It became the first transdermal treatment of Parkinson's disease in the United States.[citation needed] 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.[10] The patch was reformulated, and was reintroduced in the United States in 2012.[11]
Rotigotine was authorized as a treatment for restless legs syndrome in August 2008.[4]
Rotigotine acts as a non-selective agonist of the dopamineD1, D2, D3, and, to a lesser extent, D4 and D5receptors, with highest affinity for the D3 receptor.[15] 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.[15] In functional studies however, rotigotine behaves as a full agonist of D1, D2, and D3 with similar potencies (EC50).[15] 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.[15]
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 partialorfull 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.[16] Though it has affinity for a large number of sites as shown above, at clinical doses rotigotine behaves mostly as a selectiveD1-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.
^Bertaina-Anglade V, La Rochelle CD, Scheller DK (October 2006). "Antidepressant properties of rotigotine in experimental models of depression". European Journal of Pharmacology. 548 (1–3): 106–114. doi:10.1016/j.ejphar.2006.07.022. PMID16959244.
^Horn AS, Tepper P, Van der Weide J, Watanabe M, Grigoriadis D, Seeman P (October 1985). "Synthesis and radioreceptor binding activity of N-0437, a new, extremely potent and selective D2 dopamine receptor agonist". Pharmaceutisch Weekblad. Scientific Edition. 7 (5): 208–211. doi:10.1007/bf02307578. PMID2933633. S2CID8847550.
^Kulisevsky J, Pagonabarraga J (February 2010). "Tolerability and safety of ropinirole versus other dopamine agonists and levodopa in the treatment of Parkinson's disease: meta-analysis of randomized controlled trials". Drug Safety. 33 (2): 147–161. doi:10.2165/11319860-000000000-00000. PMID20082541. S2CID34876593.
^Wingo TS, Evatt M, Scott B, Freeman A, Stacy M (2009). "Impulse control disorders arising in 3 patients treated with rotigotine". Clinical Neuropharmacology. 32 (2): 59–62. doi:10.1097/WNF.0B013E3181684542. PMID18978496. S2CID23942499.
^ abScheller D, Ullmer C, Berkels R, Gwarek M, Lübbert H (January 2009). "The in vitro receptor profile of rotigotine: a new agent for the treatment of Parkinson's disease". Naunyn-Schmiedeberg's Archives of Pharmacology. 379 (1): 73–86. doi:10.1007/s00210-008-0341-4. PMID18704368. S2CID25112443.
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