Rotigotine

Rotigotine

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 Y
UNII	87T4T8BO2E Y
ChEMBL	CHEMBL1303 N
Chemical data
Formula	C19H25NOS
Mol. mass	315.474 g/mol
SMILES Oc1cccc3c1CCC(N(CCC)CCc2sccc2)C3
InChI InChI=1S/C19H25NOS/c1-2-11-20(12-10-17-6-4-13-22-17)16-8-9-18-15(14-16)5-3-7-19(18)21/h3-7,13,16,21H,2,8-12,14H2,1H3 Y Key:KFQYTPMOWPVWEJ-UHFFFAOYSA-N Y
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 (WED) formerly known as restless legs syndrome (RLS) in Europe and the United States. 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.

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

History

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.).

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.

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

Pharmacology

Rotigotine possesses the following in vitro receptor binding profile:

• D₁ receptor (K_i = 83 nM)
• D₂ receptor (K_i = 13.5 nM)
• D₃ receptor (K_i = 0.71 nM)
• D_4.2 receptor (K_i = 3.9 nM)
• D_4.4 receptor (K_i = 15 nM)
• D_4.7 receptor (K_i = 5.9 nM)
• D₅ receptor (K_i = 5.4 nM)

• α_1A-adrenergic receptor (K_i = 176 nM)
• α_1B-adrenergic receptor (K_i = 273 nM)
• α_2A-adrenergic receptor (K_i = 338 nM)
• α_2B-adrenergic receptor (K_i = 27 nM)
• α_2C-adrenergic receptor (K_i = 135 nM)

• 5-HT_1A receptor (K_i = 30 nM)
• 5-HT₇ receptor (K_i = 86 nM)
• H₁ receptor (K_i = 330 nM)

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 D₂-like (D₂, D₃, D₄) and D₅ receptor agonist, with its α_2B-adrenergic and 5-HT_1A activity also possibly having some low relevance.

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.

See also

• Piribedil
• Pramipexole
• Ropinirole

External links

• Rotigotine (SPM-962) - The First Once-a-Day Transdermal Patch to Treat Parkinson's Disease