Rotigotine acts as a non-selectiveagonist of thedopamineD1,D2,D3, and, to a lesser extent,D4 andD5receptors, with highestaffinity for the D3 receptor.[9] In terms ofaffinity, 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.[9] In functional studies however, rotigotine behaves as afull agonist of D1, D2, and D3 with similar potencies (EC50).[9] Its ability to activate bothD1-like andD2-like receptors is similar to the case ofapomorphine (which notably has greaterefficacy in the treatment of Parkinson's disease than D2-like-selective agonists but has suboptimalpharmacokinetic properties) andpergolide but unlikepramipexole andropinirole.[9]
All affinities listed were assayed usinghuman materials except that for α2B-adrenergic which was done withNG 108–15 cells. Rotigotine behaves as apartial orfull agonist (depending on the assay) at all dopamine receptors listed, as anantagonist at the α2B-adrenergic receptor, and as a partial agonist at the 5-HT1A receptor.[10] Though it has affinity for a large number of sites as shown above, at clinical doses rotigotine behaves mostly as aselective 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.
Rotigotine bound to the Dopamine D2 receptor PDB ID 7X2C
Initially developed at theUniversity of Groningen in 1985 as N-0437,[11] 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,[12] which firm was acquired byUCB S.A. in 2006. Schwarz completed acquisition of full rights to rotigotine from Aderis as of 2005.[13]
The drug was approved by theEuropean Medicines Agency (EMA) for use in Europe in 2006.[2] In 2007, the Neupro patch was approved by the USFood and Drug Administration (FDA).[14] 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.[15] The patch was reformulated, and was reintroduced in the United States in 2012.[16]
Rotigotine was authorized as a treatment for restless legs syndrome in the European Union in August 2008.[4]
^ab"Neupro EPAR".European Medicines Agency. 17 September 2018. Retrieved2 March 2020.
^abcChen JJ, Swope DM, Dashtipour K, Lyons KE (December 2009). "Transdermal rotigotine: a clinically innovative dopamine-receptor agonist for the management of Parkinson's disease".Pharmacotherapy.29 (12):1452–1467.doi:10.1592/phco.29.12.1452.PMID19947805.S2CID40466260.
^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.
^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.
^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.
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