Rotigotine

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Rotigotine
Rotigotin Enantiomer Structural Formulae.png
Systematic (IUPAC) name
(S)-6-[propyl(2-thiophen-2-ylethyl)amino]-5,6,7,8- tetrahydronaphthalen-1-ol
Clinical data
AHFS/Drugs.com Micromedex Detailed Consumer Information
MedlinePlus a607059
Pregnancy cat. C
Legal status Prescription only
Routes Transdermal patch
Pharmacokinetic data
Bioavailability 37% (transdermal)
Protein binding 92%
Metabolism Hepatic (CYP-mediated)
Half-life 5–7 hours
Excretion Urine (71%), Fecal (23%)
Identifiers
CAS number 92206-54-7 N
ATC code N04BC09
PubChem CID 57537
IUPHAR ligand 941
DrugBank DB05271
ChemSpider 51867 YesY
UNII 87T4T8BO2E YesY
ChEMBL CHEMBL1303 N
Chemical data
Formula C19H25NOS 
Mol. mass 315.474 g/mol
 N (what is this?)  (verify)

Rotigotine (Neupro) is a dopamine agonist of the non-ergoline class of medications indicated for the treatment of Parkinson's disease (PD) and Willis-Ekbom Disease [1] (WED) formerly known as restless legs syndrome (RLS) in Europe and the United States.[2][3] 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.[2][2]

Like other dopamine agonists, rotigotine has been shown to possess antidepressant effects and may be useful in the treatment of depression as well.[4]

History[edit]

Rotigotine was developed by Aderis Pharmaceuticals. In 1998, Aderis licensed worldwide development and commercialization rights for rotigotine to the German pharmaceutical company Schwarz Pharma (today a subsidiary of the Belgian company UCB S.A.).[5]

The drug has been approved by the EMEA for use in Europe in 2006 and is today being sold in several European countries. In 2007, the Neupro patch was approved by the Food and Drug Administration (FDA) as the first transdermal treatment of Parkinson's disease in the United States. However, as of 2008, Schwarz Pharma has recalled all Neupro patches in the United States and some in Europe because of problems with the delivery mechanism. The patch was reformulated, and was reintroduced in the United States in 2012.[6]

Rotigotine has been authorized as a treatment for restless legs syndrome since August 2008.[3]

Chemistry[edit]

Rotigotine is analogous to 7-OH-DPAT and UH-232, all three of which are aminotetralin derivatives. These compounds are similar in structure to dopamine, likely underlying their pharmacology.

Rotigotine synth.png

Cusack, N. J.; Peck, J. V.; Drugs Future 1993, 18, 1005.

Pharmacology[edit]

Rotigotine possesses the following in vitro receptor binding profile:[7]

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.[7] Though it has affinity for a large number of sites as shown above, at clinical doses rotigotine behaves mostly as a selective D2-like (D2, D3, D4) and D5 receptor agonist, with its α2B-adrenergic and 5-HT1A activity also possibly having some low relevance.

Side effects[edit]

General side effects for rotigotine may include constipation, dyskinesia, nausea, vomiting, dizziness, fatigue, insomnia, somnolence, confusion, and hallucinations.[8][9] More serious complications can include psychosis and impulse control disorders like hypersexuality, punding, and pathological gambling.[10] Mild adverse skin reactions at the patch application site may also occur.[2][9]

See also[edit]

References[edit]

  1. ^ Nightwalkers: Willis-Ekbom Foundation; Winter 2013 issue
  2. ^ a b c d Chen 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): 1452–67. doi:10.1592/phco.29.12.1452. PMID 19947805. 
  3. ^ a b Davies S (September 2009). "Rotigotine for restless legs syndrome". Drugs of Today (Barcelona, Spain : 1998) 45 (9): 663–8. doi:10.1358/dot.2009.45.9.1399952. PMID 19956807. 
  4. ^ 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): 106–14. doi:10.1016/j.ejphar.2006.07.022. PMID 16959244. 
  5. ^ Development & Commercialization of rotigotine by Aderis (Aderis Pharmaceuticals making a reference for the commercialization of rotigotine)
  6. ^ Neupro Patch Re-launches in the US
  7. ^ a b Scheller 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. PMID 18704368. 
  8. ^ Kulisevsky J, Pagonabarraga J (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 : an International Journal of Medical Toxicology and Drug Experience 33 (2): 147–61. doi:10.2165/11319860-000000000-00000. PMID 20082541. 
  9. ^ a b "A controlled trial of rotigotine monotherapy in early Parkinson's disease". Archives of Neurology 60 (12): 1721–8. December 2003. doi:10.1001/archneur.60.12.1721. PMID 14676046. 
  10. ^ 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. PMID 18978496. 

External links[edit]