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{{Short description|Parkinson medication}} |
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{{Drugbox |
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{{Use dmy dates|date=June 2020}} |
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| verifiedrevid = 445290601 |
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{{cs1 config |name-list-style=vanc |display-authors=6}} |
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{{Infobox drug |
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<!--Combo data--> |
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| Verifiedfields = changed |
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| Watchedfields = changed |
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| verifiedrevid = 447382801 |
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| type = combo |
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| type = combo |
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| image = |
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| component1 = Agonist |
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| width = |
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| class1 = ] |
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| alt = |
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| component2 = Enzyme inhibitor |
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| caption = |
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| class2 = ] |
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<!--Clinical data--> |
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<!-- Combo data --> |
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| tradename = |
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| component1 = Carbidopa |
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| class1 = ] |
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| MedlinePlus = a601068 |
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| component2 = Levodopa |
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| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X --> |
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| class2 = ] |
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| pregnancy_US = <!-- A / B / C / D / X --> |
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| legal_AU = <!-- S2, S3, S4, S5, S6, S7, S8, S9 or Unscheduled--> |
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| legal_CA = <!-- Schedule I, II, III, IV, V, VI, VII, VIII --> |
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| legal_UK = <!-- GSL, P, POM, CD, or Class A, B, C --> |
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| legal_US = <!-- OTC / Rx-only / Schedule I, II, III, IV, V --> |
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<!--Identifiers--> |
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<!-- Clinical data --> |
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| tradename = Atamet, Carbilev, Sinemet, others |
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| Drugs.com = {{drugs.com|monograph|levodopa-carbidopa}} |
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| MedlinePlus = a601068 |
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| DailyMedID = Carbidopa and levodopa |
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| pregnancy_AU = B3 |
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| pregnancy_AU_comment = |
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| pregnancy_category = |
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| routes_of_administration = ] |
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| ATC_prefix = N04 |
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| ATC_prefix = N04 |
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| ATC_suffix = BA02 |
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| ATC_suffix = BA02 |
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| ATC_supplemental = |
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<!-- Legal status --> |
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| legal_AU = S4 |
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| legal_AU_comment = |
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| legal_BR = <!-- OTC, A1, A2, A3, B1, B2, C1, C2, C3, C4, C5, D1, D2, E, F --> |
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| legal_BR_comment = |
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| legal_CA = Rx-only |
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| legal_CA_comment = |
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| legal_DE = <!-- Anlage I, II, III or Unscheduled --> |
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| legal_DE_comment = |
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| legal_NZ = <!-- Class A, B, C --> |
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| legal_NZ_comment = |
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| legal_UK = POM |
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| legal_UK_comment = |
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| legal_US = Rx-only |
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| legal_US_comment = <ref name="Duopa FDA label">{{cite web | title=Duopa- carbidopa and levodopa suspension | website=DailyMed | date=4 March 2022 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7066d371-dc6a-0d6f-7bed-e5dd4ee912da | access-date=15 August 2024}}</ref><ref name="Parcopa FDA label">{{cite web | title=Parcopa- Carbidopa and Levodopa tablet, orally disintegrating | website=DailyMed | date=5 November 2007 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=e1ff4c1f-5d6f-44a6-a0f6-d7ca2a94adb9 | access-date=15 August 2024}}</ref><ref name="Rytary FDA label">{{cite web | title=Rytary- carbidopa and levodopa capsule, extended release | website=DailyMed | date=7 December 2019 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=6c1f7cd4-de56-45c1-a734-5e77b4aeb6f7 | access-date=15 August 2024}}</ref><ref name="Sinemet FDA label">{{cite web | title=Sinemet- carbidopa and levodopa tablet | website=DailyMed | date=1 June 2022 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9b17b028-964a-473c-823d-81423535bd66 | access-date=15 August 2024}}</ref><ref name="Crexont FDA label">{{cite web | title=Crexont- carbidopa and levodopa capsule, extended release | website=DailyMed | date=7 August 2024 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=095a08b6-b0b8-4f88-b759-67e8b87287a0 | access-date=15 August 2024}}</ref> |
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| legal_EU = |
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| legal_EU_comment = |
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| legal_UN = <!-- N I, II, III, IV / P I, II, III, IV --> |
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| legal_UN_comment = |
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| legal_status = <!-- For countries not listed above --> |
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<!-- Identifiers --> |
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| CAS_number = 57308-51-7 |
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| CAS_supplemental = |
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| PubChem = 104778 |
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| PubChem = 104778 |
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| DrugBank_Ref = {{drugbankcite|correct|drugbank}} |
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| DrugBank_Ref = {{drugbankcite|correct|drugbank}} |
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| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} |
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| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} |
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| ChemSpiderID = 94585 |
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| ChemSpiderID = 94585 |
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| UNII = |
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| KEGG = D00253 |
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<!--Chemical data--> |
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| ChEBI = |
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| smiles = O=C(O)(NN)(C)Cc1cc(O)c(O)cc1.O=C(O)(N)Cc1cc(O)c(O)cc1 |
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| ChEMBL = |
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| InChI = 1/C10H14N2O4.C9H11NO4/c1-10(12-11,9(15)16)5-6-2-3-7(13)8(14)4-6;10-6(9(13)14)3-5-1-2-7(11)8(12)4-5/h2-4,12-14H,5,11H2,1H3,(H,15,16);1-2,4,6,11-12H,3,10H2,(H,13,14)/t10-;6-/m00/s1 |
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| synonyms = |
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| InChIKey = IVTMXOXVAHXCHI-YXLMWLKOBF |
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| StdInChI_Ref = {{stdinchicite|correct|chemspider}} |
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| StdInChI = 1S/C10H14N2O4.C9H11NO4/c1-10(12-11,9(15)16)5-6-2-3-7(13)8(14)4-6;10-6(9(13)14)3-5-1-2-7(11)8(12)4-5/h2-4,12-14H,5,11H2,1H3,(H,15,16);1-2,4,6,11-12H,3,10H2,(H,13,14)/t10-;6-/m00/s1 |
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| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} |
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| StdInChIKey = IVTMXOXVAHXCHI-YXLMWLKOSA-N |
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}} |
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}} |
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<!-- Definition and medical uses --> |
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'''Carbidopa/levodopa''' is the combination of ] and ] and is used to treat ]<ref name="pmid17078781"/> and ] (DRD). It is sold under several brand names, including '''Sinemet''', '''Parcopa''', and '''Atamet'''. The generic name under the ] system is '''Co-careldopa'''. |
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'''Carbidopa/levodopa''', also known as '''levocarb''' and '''co-careldopa''', is the combination of the two medications ] and ].<ref name=AHFS2015>{{cite web|title=Levodopa/Carbidopa|url=https://www.drugs.com/monograph/levodopa-carbidopa.html|publisher=The American Society of Health-System Pharmacists|access-date=21 August 2015|url-status=live|archive-url=https://web.archive.org/web/20150924003553/http://www.drugs.com/monograph/levodopa-carbidopa.html|archive-date=24 September 2015}}</ref> It is primarily used to manage the symptoms of ], but it does not slow down the disease or stop it from getting worse.<ref name=AHFS2015/> It is taken ].<ref name=AHFS2015/> It can take two to three weeks of treatment before benefits are seen.<ref name=Nurse2014/> Each dose then begins working in about ten minutes to two hours with a duration of effect of about five hours.<ref name=Nurse2014>{{cite book | chapter = Chapter 15: Antiparkinson Drugs |title=Pharmacology and the Nursing Process|date=2014|publisher=Elsevier Health Sciences|isbn=9780323293617|page=246| chapter-url=https://books.google.com/books?id=_bnwAwAAQBAJ&pg=PA246|url-status=live|archive-url=https://web.archive.org/web/20170705223056/https://books.google.ca/books?id=_bnwAwAAQBAJ&pg=PA246|archive-date=5 July 2017}}</ref><ref name="Complications in anesthesia">{{cite book| vauthors = Atlee JL |title=Complications in anesthesia|date=2007|publisher=Elsevier/Saunders|location=Philadelphia|isbn=9781416022152|page=490|edition=2nd|url=https://books.google.com/books?id=qVdr5MVok1YC&pg=PA490|url-status=live|archive-url=https://web.archive.org/web/20170315175203/https://books.google.ca/books?id=qVdr5MVok1YC&pg=PA490|archive-date=15 March 2017}}</ref><ref name=Ox2015>{{cite book |title=The new Parkinson's disease treatment book : partnering with your doctor to get the most from your medications |date=2015 |publisher=Oxford University Press |isbn=9780190231866 |page=227 |edition=2 |url=https://books.google.com/books?id=vNsACgAAQBAJ&pg=PP227}}</ref> |
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<!-- Side effects and mechanism --> |
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== Benefits of the combination drug == |
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Common side effects include ] and nausea.<ref name=AHFS2015/> More serious side effects include depression, ], sudden onset of sleepiness, ], and increased risk-taking behavior.<ref name=AHFS2015/><ref name=Ric2013/> Carbidopa prevents the breakdown of levodopa outside the brain.<ref name=Ric2013/> In the brain, levodopa is broken down into ], its active form.<ref name=Ric2013/> Carbidopa also helps prevent some of the nausea which levodopa causes.<ref>{{cite book | vauthors = Ahlskog JE |title=Parkinson's Disease Treatment Guide for Physicians |date=2009 |publisher=Oxford University Press |isbn=978-0-19-537177-2 |page=124 |url=https://books.google.com/books?id=OkEdjS_vEDYC&pg=PA124 |language=en}}</ref> |
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Levodopa is converted to ] via the action of a naturally occurring ] called ]. This occurs both in the peripheral circulation and in the ] after levodopa has crossed the ]. Activation of central dopamine receptors improves the symptoms of Parkinson's Disease, however, activation of peripheral dopamine receptors causes nausea and vomiting. For this reason levodopa is usually administered in combination with a ], in this case carbidopa, which is very polar (and charged at physiologic pH) and cannot cross the blood brain barrier, however prevents peripheral conversion of levodopa to dopamine and thereby reduces the unwanted peripheral side-effects of levodopa. Use of carbidopa also increases the quantity of levodopa in the bloodstream that is available to enter the brain. |
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<!-- Society and culture --> |
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== History== |
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It is on the ].<ref name="WHO21st">{{cite book | vauthors = ((World Health Organization)) | title = World Health Organization model list of essential medicines: 21st list 2019 | year = 2019 | hdl = 10665/325771 | author-link = World Health Organization | publisher = World Health Organization | location = Geneva | id = WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO | hdl-access=free }}</ref> It is available as a ].<ref name=Ric2013>{{cite book| vauthors = Hamilton RJ |title=Tarascon pocket pharmacopoeia.|date=2013|publisher=Jones & Bartlett Learning|location=Burlington, MA.|isbn=9781449673635|page=303|edition=14th|url=https://books.google.com/books?id=Ti4xt1-9fLkC&pg=PA303|url-status=live|archive-url=https://web.archive.org/web/20160112052652/https://books.google.ca/books?id=Ti4xt1-9fLkC&pg=PA303|archive-date=12 January 2016}}</ref> In 2022, it was the 278th most commonly prescribed medication in the United States, with more than 700,000 prescriptions.<ref>{{cite web | title=The Top 300 of 2022 | url=https://clincalc.com/DrugStats/Top300Drugs.aspx | website=ClinCalc | access-date=30 August 2024 | archive-date=30 August 2024 | archive-url=https://web.archive.org/web/20240830202410/https://clincalc.com/DrugStats/Top300Drugs.aspx | url-status=live }}</ref><ref>{{cite web | title = Carbidopa; Levodopa Drug Usage Statistics, United States, 2013 - 2022 | website = ClinCalc | url = https://clincalc.com/DrugStats/Drugs/CarbidopaLevodopa | access-date = 30 August 2024 }}</ref> |
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In 1960 the Austrian biochemist ], while at the ], examined results of autopsies of patients who had died with Parkinson's disease. He suggested that the disease was associated with, or caused by, a reduction in the levels of dopamine in the ] of the brain. Since dopamine itself did not enter the brain, he tried treating twenty patients with a ] of ] (DOPA), which could enter the brain and be converted there to dopamine by the action of DOPA decarboxylase. His results were positive, as were those of another trial in Montreal run by ]. Unfortunately, other investigators were unable to replicate these early results, and the use of DOPA remained in question until 1967, when ] at the ] in Upton, New York, used megadoses of DOPA, up to 16 grams per day. Not long after these results became known, Curt Porter at ] showed that L-DOPA was the active ], thus reducing the effective dose to half.<ref name=Scriabine/> |
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==Medical uses== |
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With L-DOPA identified as the active form, Alfred Pletscher and his colleagues at ] synthesized ], an inhibitor of DOPA decarboxylase, which further reduced the required dose. A drug combining L-DOPA with benserazide was marketed under the brand name of Madopar. Independent work was carried out by Victor Lotti at Merck in West Point, Pennsylvania. Merck had already synthesized and patented carbidopa, another dopa decarboxylase inhibitor in 1962, and in 1971 Lotti showed that the use of the L-form of carbidopa, further reduced the therapeutic dose of L-DOPA into the range of 1 to 2 grams per day. The combination of L-carbidopa and L-DOPA was marketed under the brand name of Sinemet.<ref name=Scriabine/> |
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] |
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===Parkinson's disease=== |
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In 1991 the manufacture and sale of Sinemet was taken over by a new joint venture, Dupont Merck Pharmaceutical Company. That same year approvals for a sustained release formulation (Sinemet CR) which could be taken less frequently were also obtained.<ref name=Dupont/> ] purchased Merck's share in the joint venture in 1998 and began operating the company as Dupont Pharmaceuticals (later Dupont Pharma), but Merck continued to manufacture the drug for Dupont.<ref name=listingdrugs/> Starting in late 2009 and continuing into 2011 Merck stopped manufacturing the drug while awaiting regulatory approvals due to a change in the supplier of the active ingredient. This resulted in shortages of the brand name products Sinemet and Sinemet CR, although alternative generic versions were still available.<ref name=Bibmomma/> |
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It is primarily used to improve the symptoms of ] but does not change the course of the disease.<ref name=AHFS2015/> It can take two to three weeks of treatment before benefits are seen.<ref name=Nurse2014/> Each dose then begins working in about ten minutes to two hours depending on the formulation, with a duration of effect of about five hours.<ref name="Nurse2014"/><ref name="Complications in anesthesia"/><ref name=Ox2015/> |
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A formulation that can be given in an intra-] pump, known as Duodopa, is being developed.<ref>{{cite web|url=http://hc-sc.gc.ca/dhp-mps/prodpharma/notices-avis/conditions/duodopa_fs_fd_139124-eng.php |title=Fact sheet - Duodopa (levodopa/carbidopa intestinal gel) |publisher=Hc-sc.gc.ca |date=11 August 2010 |access-date=5 February 2013 |url-status=dead |archive-url=https://web.archive.org/web/20130111161648/http://www.hc-sc.gc.ca/dhp-mps/prodpharma/notices-avis/conditions/duodopa_fs_fd_139124-eng.php |archive-date=11 January 2013 }}</ref><ref>{{cite web |url=http://www.duodopa.co.uk/Pages/DuodopaTherapy.aspx | publisher = Abbott Healthcare | title = Information on Duodopa | work = Duodopa.co.uk |access-date=5 February 2013 |url-status=dead |archive-url=https://web.archive.org/web/20130101124710/http://www.duodopa.co.uk/pages/DuodopaTherapy.aspx |archive-date=1 January 2013 }}</ref> |
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== See also == |
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* ] |
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* ] |
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* ] in combination with ] |
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== References == |
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===Other=== |
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Other uses include for ] (DRD) and ].<ref name=Ric2013/><ref name="AFP2013">{{cite journal | vauthors = Ramar K, Olson EJ | title = Management of common sleep disorders | journal = American Family Physician | volume = 88 | issue = 4 | pages = 231–238 | date = August 2013 | pmid = 23944726 | url = https://www.aafp.org/link_out?pmid=23944726 }}</ref><ref name="NEUR2021">{{cite journal | vauthors = Gossard TR, Trotti LM, Videnovic A, St Louis EK | title = Restless Legs Syndrome: Contemporary Diagnosis and Treatment | journal = Neurotherapeutics | volume = 18 | issue = 1 | pages = 140–155 | date = January 2021 | pmid = 33880737 | pmc = 8116476 | doi = 10.1007/s13311-021-01019-4 }}</ref> Using carbidopa/levodopa may lead to augmentation syndrome, with increasing persistence of restless legs syndrome, and increasing severity.<ref name ="NEUR2021"/> |
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<references><!-- |
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--> |
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<ref name="pmid17078781">{{cite journal |author=Nyholm D |title=Enteral levodopa/carbidopa gel infusion for the treatment of motor fluctuations and dyskinesias in advanced Parkinson's disease |journal=Expert review of neurotherapeutics |volume=6 |issue=10 |pages=1403–11 |year=2006 |month=October |pmid=17078781 |doi=10.1586/14737175.6.10.1403 |url=http://www.future-drugs.com/doi/abs/10.1586/14737175.6.10.1403?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dncbi.nlm.nih.gov}}</ref><!-- |
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--> |
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<ref name=Scriabine>Scriabine, Alexander (1999). "Discovery and Development of Major Drugs Currently in Use", pp. 222–223 in ''Pharmaceutical Innovation: Revolutionizing Human Health'', edited by Ralph Landau, Basil Achilladelis, and Alexander Scriabine. Philadelphia: Chemical Heritage Press. ISBN 9780941901215.</ref><!-- |
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--> |
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<ref name=Dupont> at Dupont Heritage.</ref><!-- |
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--> |
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<ref name=listingdrugs> at listingdrugs.com</ref><!-- |
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--> |
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<ref name=Bibmomma> at Bibmomma's Blog – Reflections of an early onset Parkinson's patient.</ref><!-- |
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--> |
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</references> |
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There is tentative evidence that it is useful in ] when used with other treatments.<ref>{{cite journal | vauthors = DeSantis D | title = Amblyopia | journal = Pediatric Clinics of North America | volume = 61 | issue = 3 | pages = 505–518 | date = June 2014 | pmid = 24852148 | doi = 10.1016/j.pcl.2014.03.006 }}</ref> |
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== External links == |
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* at MedlinePlus Drug Information |
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==Side effects== |
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* at Merck Frosst Canada |
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* {{Dead link}} |
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Common side effects include dizziness, drowsiness, blurred vision, vomiting, nausea, dry mouth, low appetite, heartburn, diarrhea, constipation, frequent sneezing, stuffiness of the nose, any of the symptoms of ordinary common cold, cough, muscle pain, hallucinations, numbness or a tingling sensation, disturbances of sleep, skin rash, itching, and/or headache.<ref name="rxlist">{{Cite web|url=https://www.rxlist.com/sinemet-side-effects-drug-center.htm|title = Side Effects of Sinemet (Carbidopa-Levodopa), Warnings, Uses | work = RxList | editor = Cunha JP | date = 26 April 2023 }}</ref> |
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Less common, but more serious, side effects can include very frequent blinking or twitching of the eyes, fainting, mood changes such as confusion, depression, hallucinations, thoughts of suicide, or unusual strong urges (such as increased gambling), increases in the sex-drive, delusions (strongly-felt belief in something which is obviously not true), worsening of involuntary movements or spasms, and/or other ]. |
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== Mechanism of action == |
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Levodopa is converted to ] via the action of a naturally occurring ] called ].<ref>{{cite book |doi=10.1016/B978-1-4160-3074-4.X1000-4 |title=Clinical Neurology for Psychiatrists |date=2007 |isbn=978-1-4160-3074-4 |editor1-first=David Myland |editor1-last=Kaufman }}{{pn|date=December 2024}}</ref> This occurs both in the peripheral circulation and in the ] after levodopa has crossed the ]. Activation of central dopamine receptors improves the symptoms of Parkinson's disease; however, activation of peripheral dopamine receptors causes nausea and vomiting. For this reason levodopa is usually administered in combination with a ], in this case carbidopa, which is very polar (and charged at physiologic pH) and cannot cross the blood brain barrier, however prevents peripheral conversion of levodopa to dopamine and thereby reduces the unwanted peripheral side effects of levodopa. Use of carbidopa also increases the quantity of levodopa in the bloodstream that is available to enter the brain. |
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==History== |
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In 1960, the Austrian biochemist ], while at the ], examined results of autopsies of patients who had died with Parkinson's disease. He suggested that the disease was associated with, or caused by, a reduction in the levels of dopamine in the ] of the brain. Since dopamine itself did not enter the brain, he tried treating twenty patients with a ] of ] (DOPA), which could enter the brain and be converted there to dopamine by the action of DOPA decarboxylase. His results were positive, as were those of another trial in Montreal run by ]. Unfortunately, other investigators were unable to replicate these early results, and the use of DOPA remained in question until 1967, when ] at the ] in Upton, New York, used megadoses of DOPA, up to 16 grams per day. Not long after these results became known, Curt Porter at ] showed that L-DOPA was the active ], thus reducing the effective dose to half.<ref name=Scriabine/> |
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With L-DOPA identified as the active form, Alfred Pletscher and his colleagues at ] synthesized ], an inhibitor of DOPA decarboxylase, which further reduced the required dose. A drug combining L-DOPA with benserazide was marketed under the brand name of Madopar. Independent work was carried out by Victor Lotti at Merck in West Point, Pennsylvania. Merck had already synthesized and patented carbidopa, another dopa decarboxylase inhibitor in 1962, and in 1971 Lotti showed that the use of the L-form of carbidopa, further reduced the therapeutic dose of L-DOPA. The combination of L-carbidopa and L-DOPA was marketed under the brand name of Sinemet.<ref name=Scriabine>{{cite book | vauthors = Scriabine A | date = 1999 | chapter = Discovery and Development of Major Drugs Currently in Use | pages = 222–223 | title = Pharmaceutical Innovation: Revolutionizing Human Health | veditors = Landau R, Achilladelis B, Scriabine A | location = Philadelphia | publisher = Chemical Heritage Press | isbn = 978-0-941901-21-5}}</ref> |
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==Society and culture== |
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=== Economics === |
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It is available as a ].<ref name=Ric2013/> |
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===Names=== |
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{{unreferenced section|date=October 2015}} |
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The generic name under the ] system is Co-careldopa. |
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It is sold under several brand names, including Sinemet (]), Pharmacopa, Atamet, Apo-Levocarb, Duodopa, Kinson, and Pharmacopa, among others. |
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Extended-release formulations are sold as Rytary and Sinemet-CR. An extended-release enteral solution is sold as Duopa. |
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===Shortages=== |
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In 1991, Merck licensed the rights to the manufacture and sale of Sinemet to a newly created joint venture, DuPont Merck Pharmaceutical Company. That same year, approvals for a sustained release formulation (Sinemet CR) which could be taken less frequently were also obtained.<ref name=DuPont>{{cite web | url = http://www2.dupont.com/Heritage/en_US/related_topics/sinemet.html | title = Sinemet | archive-url = https://web.archive.org/web/20110511062513/http://www2.dupont.com/Heritage/en_US/related_topics/sinemet.html | archive-date=11 May 2011 | work = Dupont Heritage }}</ref> ] purchased Merck's share in the joint venture in 1998 and began operating the company as DuPont Pharmaceuticals (DuPont Pharma), but Merck continued to manufacture the drug for DuPont.<ref name=listingdrugs>{{cite web | url = http://www.listingdrugs.com/drugs/SINEMET.HTM | title = SINEMET | work = listingdrugs.com | archive-url = https://web.archive.org/web/20120503200925/http://www.listingdrugs.com/drugs/SINEMET.HTM | archive-date=3 May 2012 }}</ref> Starting in late 2009 and continuing into 2011 Merck stopped manufacturing the drug while awaiting regulatory approvals due to a change in the supplier of the active ingredient. This resulted in shortages of the brand name products Sinemet and Sinemet CR, although alternative generic versions were still available.<ref name=Bibmomma>{{cite web | url = http://bibmomma.wordpress.com/2010/09/01/letter-from-merck-about-sinemet-shortage/ | title = Letter From MERCK About SINEMET Shortage | archive-url = https://web.archive.org/web/20110703041854/http://bibmomma.wordpress.com/2010/09/01/letter-from-merck-about-sinemet-shortage/ | archive-date=3 July 2011 | work = Bibmomma's Blog – Reflections of an early onset Parkinson's patient }}</ref> |
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== References == |
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{{DEFAULTSORT:Carbidopa Levodopa}} |
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