Rotigotine

Overview

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.[1][2] WP

Like other dopamine agonists, rotigotine has been shown to possess antidepressant effects and may be useful in the treatment of depression as well.[3] WP

Risks and side effects

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.[1][4][5][6] WP

Pharmacology

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.[7] WP⚠ A table follows this text in the source and is not copied here. Open the source to see it.

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.[8] WP

History

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.[9][10][11] WP⚠ Wikipedia itself has flagged this text: citation needed.

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.[12–15] WP⚠ Wikipedia itself has flagged this text: citation needed.

Rotigotine was authorized as a treatment for restless legs syndrome in the European Union in August 2008.[2] WP

Chemistry

Formula

C19H25NOS PC

CAS number

92206-54-7 PC

Molar mass (g/mol)

315.5 PC

IUPAC name (computed by PubChem)

6-[propyl(2-thiophen-2-ylethyl)amino]-5,6,7,8-tetrahydronaphthalen-1-ol PC

SMILES

CCCN(CCC1=CC=CS1)C2CCC3=C(C2)C=CC=C3O PC

InChIKey

KFQYTPMOWPVWEJ-UHFFFAOYSA-N PC

PubChem CID

57537

Harm reduction information

No harm reduction data is on file for this compound yet. That means no dose, timing or combination data from PsychonautWiki or TripSit. Please don't guess a dose from similar compounds. If you have taken it and feel unwell, contact emergency services or a poison control center.

User reports

Pop culture

No references added yet.

Sources

1. Journal / agency Chen JJ, Swope DM, Dashtipour K, Lyons KE. Transdermal rotigotine: a clinically innovative dopamine-receptor agonist for the management of Parkinson's disease. Pharmacotherapy. December 2009. doi:10.1592/phco.29.12.1452 · PMID 19947805
2. Journal / agency Davies S. Rotigotine for restless legs syndrome. Drugs of Today. September 2009. doi:10.1358/dot.2009.45.9.1399952 · PMID 19956807
3. Journal / agency Bertaina-Anglade V, La Rochelle CD, Scheller DK. Antidepressant properties of rotigotine in experimental models of depression. European Journal of Pharmacology. October 2006. doi:10.1016/j.ejphar.2006.07.022 · PMID 16959244
4. Journal / agency Kulisevsky J, Pagonabarraga J. 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. February 2010. doi:10.2165/11319860-000000000-00000 · PMID 20082541
5. Journal / agency Parkinson Study Group. A controlled trial of rotigotine monotherapy in early Parkinson's disease. Archives of Neurology. December 2003. doi:10.1001/archneur.60.12.1721 · PMID 14676046
6. Journal / agency Wingo TS, Evatt M, Scott B, Freeman A, Stacy M. Impulse control disorders arising in 3 patients treated with rotigotine. Clinical Neuropharmacology. 2009. doi:10.1097/WNF.0B013E3181684542 · PMID 18978496
7. Journal / agency Wood M, Dubois V, Scheller D, Gillard M. Rotigotine is a potent agonist at dopamine D1 receptors as well as at dopamine D2 and D3 receptors. British Journal of Pharmacology. February 2015. doi:10.1111/bph.12988 · PMID 25339241 · PMC4314200
8. Journal / agency Scheller D, Ullmer C, Berkels R, Gwarek M, Lübbert H. The in vitro receptor profile of rotigotine: a new agent for the treatment of Parkinson's disease. Naunyn-Schmiedeberg's Archives of Pharmacology. January 2009. doi:10.1007/s00210-008-0341-4 · PMID 18704368
9. Journal / agency Horn AS, Tepper P, Van der Weide J, Watanabe M, Grigoriadis D, Seeman P. Synthesis and radioreceptor binding activity of N-0437, a new, extremely potent and selective D2 dopamine receptor agonist. Pharmaceutisch Weekblad. Scientific Edition. October 1985. doi:10.1007/bf02307578 · PMID 2933633
10. Other Development & Commercialization of rotigotine by Aderis (Aderis Pharmaceuticals making a reference for the commercialization of rotigotine)
11. Other SCHWARZ PHARMA ACQUIRES REMAINING RIGHTS TO ROTIGOTINE FROM ADERIS | FDAnews
12. Journal / agency Neupro EPAR. 17 September 2018
13. Journal / agency PubChem. Rotigotine
14. Journal / agency Zhou CQ, Li SS, Chen ZM, Li FQ, Lei P, Peng GG. Rotigotine transdermal patch in Parkinson's disease: a systematic review and meta-analysis. PLOS ONE. 23 July 2013. doi:10.1371/journal.pone.0069738 · PMID 23936090 · PMC3720658
15. Other Neupro Patch Re-launches in the US

Text and values on this page are quoted from Wikipedia (CC BY-SA 4.0), PubChem (public domain). Each value links to the exact revision it came from.