| 词条 | Rotigotine |
| 释义 |
| Verifiedfields = changed | verifiedrevid = 464383949 | IUPAC_name = (S)-6-[Propyl(2-thiophen-2-ylethyl)amino]-5,6,7,8- tetrahydronaphthalen-1-ol | image = Rotigotine.svg | tradename = Neupro | Drugs.com = {{drugs.com|CONS|rotigotine_transdermal_patch}} | MedlinePlus = a607059 | pregnancy_AU = B3 | pregnancy_US = C | licence_EU = yes | legal_AU = S4 | legal_status = Rx-only | routes_of_administration = Transdermal patch | bioavailability = 37% (transdermal) | protein_bound = 92% | metabolism = Hepatic (CYP-mediated) | elimination_half-life = 5–7 hours | excretion = Urine (71%), Fecal (23%) | CAS_number_Ref = {{cascite|changed|??}} | CAS_number = 99755-59-6 | ATC_prefix = N04 | ATC_suffix = BC09 | PubChem = 57537 | IUPHAR_ligand = 941 | DrugBank_Ref = {{drugbankcite|correct|drugbank}} | DrugBank = DB05271 | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | ChemSpiderID = 51867 | UNII_Ref = {{fdacite|correct|FDA}} | UNII = 87T4T8BO2E | KEGG = D05768 | ChEMBL_Ref = {{ebicite|changed|EBI}} | ChEMBL = 1303 | C=19 | H=25 | N=1 | O=1 | S=1 | smiles = Oc1cccc3c1CCC(N(CCC)CCc2sccc2)C3 | StdInChI_Ref = {{stdinchicite|correct|chemspider}} | StdInChI = 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 | StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} | StdInChIKey = KFQYTPMOWPVWEJ-UHFFFAOYSA-N }}Rotigotine (trade name Neupro) is a dopamine agonist of the non-ergoline class of medications indicated for the treatment of Parkinson's disease (PD) and restless legs syndrome (RLS).[1][2] 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][1] Like other dopamine agonists, rotigotine has been shown to possess antidepressant effects and may be useful in the treatment of depression as well.[3] HistoryRotigotine was first developed in 1985 as N-0437 by a team from the University of Groningen.[4] Development was then continued 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.[2] Side effectsGeneral side effects for rotigotine may include constipation, dyskinesia, nausea, vomiting, dizziness, fatigue, insomnia, somnolence, confusion, and hallucinations.[7][8] More serious complications can include psychosis and impulse control disorders like hypersexuality, punding, and pathological gambling.[9] Mild adverse skin reactions at the patch application site may also occur.[1][8] PharmacologyRotigotine 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.[10] 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.[10] In functional studies however, rotigotine behaves as a full agonist of D1, D2, and D3 with similar potencies (EC50).[10] 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.[10] Rotigotine possesses the following in vitro receptor binding profile:[11] {{Col-begin}}{{Col-1-of-3}}
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.[11] 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. See also
References1. ^1 2 3 {{cite journal | vauthors = Chen JJ, Swope DM, Dashtipour K, Lyons KE | title = Transdermal rotigotine: a clinically innovative dopamine-receptor agonist for the management of Parkinson's disease | journal = Pharmacotherapy | volume = 29 | issue = 12 | pages = 1452–67 | date = December 2009 | pmid = 19947805 | doi = 10.1592/phco.29.12.1452 }} 2. ^1 {{cite journal | author = Davies S | title = Rotigotine for restless legs syndrome | journal = Drugs of Today (Barcelona, Spain : 1998) | volume = 45 | issue = 9 | pages = 663–8 |date=September 2009 | pmid = 19956807 | doi = 10.1358/dot.2009.45.9.1399952 | url = http://journals.prous.com/journals/servlet/xmlxsl/pk_journals.xml_summaryn_pr?p_JournalId=4&p_RefId=1399952}} 3. ^{{cite journal |vauthors=Bertaina-Anglade V, La Rochelle CD, Scheller DK | title = Antidepressant properties of rotigotine in experimental models of depression | journal = European Journal of Pharmacology | volume = 548 | issue = 1–3 | pages = 106–14 |date=October 2006 | pmid = 16959244 | doi = 10.1016/j.ejphar.2006.07.022 | url = http://linkinghub.elsevier.com/retrieve/pii/S0014-2999(06)00757-6}} 4. ^{{cite journal | pmid = 2933633 | volume=7 | issue=5 | title=Synthesis and radioreceptor binding activity of N-0437, a new, extremely potent and selective D2 dopamine receptor agonist | year=1985 | journal=Pharm Weekbl Sci | pages=208–11 | vauthors=Horn AS, Tepper P, Van der Weide J, Watanabe M, Grigoriadis D, Seeman P | doi=10.1007/bf02307578}} 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. ^{{cite journal |vauthors=Kulisevsky J, Pagonabarraga J | title = Tolerability and safety of ropinirole versus other dopamine agonists and levodopa in the treatment of Parkinson's disease: meta-analysis of randomized controlled trials | journal = Drug Safety | volume = 33 | issue = 2 | pages = 147–61 | year = 2010 | pmid = 20082541 | doi = 10.2165/11319860-000000000-00000 | url = http://content.wkhealth.com/linkback/openurl?issn=0114-5916&volume=33&issue=2&spage=147}} 8. ^1 {{cite journal | title = A controlled trial of rotigotine monotherapy in early Parkinson's disease | journal = Archives of Neurology | volume = 60 | issue = 12 | pages = 1721–8 | date = December 2003 | pmid = 14676046 | doi = 10.1001/archneur.60.12.1721 | url = http://archneur.ama-assn.org/cgi/pmidlookup?view=long&pmid=14676046 | archive-url = https://archive.is/20120224050013/http://archneur.ama-assn.org/cgi/pmidlookup?view=long&pmid=14676046 | dead-url = yes | archive-date = 2012-02-24 }} 9. ^{{cite journal |vauthors=Wingo TS, Evatt M, Scott B, Freeman A, Stacy M | title = Impulse control disorders arising in 3 patients treated with rotigotine | journal = Clinical Neuropharmacology | volume = 32 | issue = 2 | pages = 59–62 | year = 2009 | pmid = 18978496 | doi = 10.1097/WNF.0B013E3181684542 | url = http://meta.wkhealth.com/pt/pt-core/template-journal/lwwgateway/media/landingpage.htm?issn=0362-5664&volume=32&issue=2&spage=59}} 10. ^1 2 3 {{cite journal|last1=Wood|first1=Martyn|last2=Dubois|first2=Vanessa|last3=Scheller|first3=Dieter|last4=Gillard|first4=Michel|title=Rotigotine is a potent agonist at dopamine D1receptors as well as at dopamine D2and D3receptors|journal=British Journal of Pharmacology|volume=172|issue=4|year=2015|pages=1124–1135|issn=0007-1188|doi=10.1111/bph.12988|pmid=25339241|pmc=4314200}} 11. ^1 {{cite journal |vauthors=Scheller D, Ullmer C, Berkels R, Gwarek M, Lübbert H | title = The in vitro receptor profile of rotigotine: a new agent for the treatment of Parkinson's disease | journal = Naunyn-Schmiedeberg's Archives of Pharmacology | volume = 379 | issue = 1 | pages = 73–86 |date=January 2009 | pmid = 18704368 | doi = 10.1007/s00210-008-0341-4 }} External links
5 : Amines|Dopamine agonists|Phenols|Tetralins|Thiophenes |
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