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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2014/10/28 22:56:34」(JST)

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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

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

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 synthesis:^[7]

Pharmacology

Rotigotine possesses the following in vitro receptor binding profile:^[8]

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.^[8] 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.^[9]^[10] More serious complications can include psychosis and impulse control disorders like hypersexuality, punding, and pathological gambling.^[11] Mild adverse skin reactions at the patch application site may also occur.^[2]^[10]

References

^ Nightwalkers: Willis-Ekbom Foundation; Winter 2013 issue
^ ^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.
^ ^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.
^ 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.
^ Development & Commercialization of rotigotine by Aderis (Aderis Pharmaceuticals making a reference for the commercialization of rotigotine)
^ Neupro Patch Re-launches in the US
^ Cusack, N. J.; Peck, J. V.; Drugs Future 1993, 18, 1005.
^ ^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.
^ 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.
^ ^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.
^ 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

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

UpToDate Contents

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1. 成人におけるむずむず脚症候群／Willis-Ekbom病の治療 treatment of restless legs syndrome willis ekbom disease in adults
2. パーキンソン病の薬理学的治療 pharmacologic treatment of parkinson disease
3. パーキンソン病における症状の変動およびジスキネジア motor fluctuations and dyskinesia in parkinson disease
4. 妊娠中および授乳中のむずむず脚症候群／Willis-Ekbom病 restless legs syndrome willis ekbom disease during pregnancy and lactation
5. 神経疾患を有する手術患者の周術期ケア perioperative care of the surgical patient with neurologic disease

English Journal

Report of Two Never Treated Adult Sisters with Aromatic L-Amino Acid Decarboxylase Deficiency: A Portrait of the Natural History of the Disease or an Expanding Phenotype?

Leuzzi V1, Mastrangelo M, Polizzi A, Artiola C, van Kuilenburg AB, Carducci C, Ruggieri M, Barone R, Tavazzi B, Abeling NG, Zoetekouw L, Sofia V, Zappia M, Carducci C.
JIMD reports.JIMD Rep.2014 May 1. [Epub ahead of print]
Two sisters were diagnosed in their adulthood with aromatic L-amino acid decarboxylase (AADC) deficiency (OMIM#608643). They experienced early myasthenia-like manifestations, myoclonic jerks, oculogyric crises, tremors, and developmental delay during childhood; clinical stabilization afterwards; and
PMID 24788355

Dopaminergic agonists in Parkinson's disease.

Alonso Cánovas A1, Luquin Piudo R2, García Ruiz-Espiga P3, Burguera JA4, Campos Arillo V5, Castro A6, Linazasoro G7, López Del Val J8, Vela L9, Martínez Castrillo JC10.
Neurologia (Barcelona, Spain).Neurologia.2014 May;29(4):230-241. doi: 10.1016/j.nrl.2011.04.012. Epub 2011 Jul 2.
BACKGROUND: Non-ergoline dopamine agonists (DA) are effective treatments for Parkinson's disease (PD). This review presents the pharmacology, evidence of efficacy and safety profile of pramipexole, ropinirole, and rotigotine, and practical recommendations are given regarding their use in clinical pr
PMID 21724302

Meta-analysis of the efficacy and safety of long-acting non-ergot dopamine agonists in Parkinson's disease.

Zhou CQ1, Zhang JW2, Wang M3, Peng GG4.
Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia.J Clin Neurosci.2014 Apr 28. pii: S0967-5868(14)00060-5. doi: 10.1016/j.jocn.2013.10.041. [Epub ahead of print]
A meta-analysis of randomized controlled trials (RCT) was performed to evaluate the efficacy and safety of long-acting non-ergot dopamine agonists (NEDA) versus placebo in Parkinson's disease (PD). A comprehensive literature search up to February 2013 was performed, and the weighted mean differences
PMID 24786715

Japanese Journal

パーキンソン病治療薬 (新薬展望 2009) -- (治療における最近の新薬の位置付け<薬効別>--新薬の広場)

頼高朝子,服部信孝
医薬ジャ-ナル 45(S1), 324-327, 2009
NAID 40016465081

Determination of the dopamine agonist rotigotine in microdialysates from the rat brain by microbore column liquid chromatography with electrochemical detection

KEHR Jan,HU Xiao-Jing,YOSHITAKE Takashi,SCHELLER Dieter
Journal of chromatography. B, Analytical technologies in the biomedical and life sciences 845(1), 109-113, 2007-01-01
NAID 10019944257

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リンク元

「ロチゴチン」

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
ATC code	N04BC09
PubChem	CID 57537
IUPHAR ligand	941
DrugBank	DB05271
ChemSpider	51867
UNII	87T4T8BO2E
ChEMBL	CHEMBL1303
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 ; Key:KFQYTPMOWPVWEJ-UHFFFAOYSA-N ;
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　　[★]

英: rotigotine
商: ニュープロ

[1] Nightwalkers: Willis-Ekbom Foundation; Winter 2013 issue

[pmid19947805-2] 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.

[pmid19956807-3] 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.

[pmid16959244-4] 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] Cusack, N. J.; Peck, J. V.; Drugs Future 1993, 18, 1005.

[pmid18704368-8] 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.

[pmid20082541-9] 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.

[pmid14676046-10] "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.

[pmid18978496-11] 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.

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rotigotine