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Revision as of 09:47, 17 November 2011 editBeetstra (talk | contribs)Edit filter managers, Administrators172,031 edits Saving copy of the {{drugbox}} taken from revid 461039912 of page L-DOPA for the Chem/Drugbox validation project (updated: 'DrugBank').		Latest revision as of 05:03, 5 January 2025 edit SimLibrarian (talk | contribs)Extended confirmed users124,451 editsm MOS:PERCENT, non-breaking space use (MOS:NBSP)Tag: Visual edit
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			{{Short description|Dopaminergic medication}}
	{{ambox | text = This page contains a copy of the infobox ({{tl|drugbox}}) taken from revid of page ] with values updated to verified values.}}
			{{About|<small>L</small>-DOPA (levodopa) as a medication and supplement|its role as a biological compound|L-DOPA}}
	{{Drugbox
			{{cs1 config|name-list-style=vanc|display-authors=6}}
	| Verifiedfields = changed
			{{Infobox drug
	| verifiedrevid = 415564129
			| Watchedfields = changed
	| IUPAC_name = (''S'')-2-amino-3-(3,4-dihydroxyphenyl)<br />propanoic acid
			| verifiedrevid = 461087196
			| IUPAC_name = (''S'')-2-Amino-3-(3,4-dihydroxyphenyl)propanoic acid
	| image = 3,4-Dihydroxy-L-phenylalanin (Levodopa).svg		| image = 3,4-Dihydroxy-L-phenylalanin (Levodopa).svg
	| width = 200		| width =
			| caption = ] of levodopa
	| image2 = Levodopa3D.PNG
			| image2 = L-DOPA-from-xtal-view-2-3D-bs-17.png
	| drug_name = <small>L</small>-DOPA
			| width2 = 180px
			| caption2 = ] of the ]ic form of levodopa found in the ]<ref>{{ cite journal | title = Experimental and theoretical determination of electronic properties in Ldopa | vauthors = Howard ST, Hursthouse MB, Lehmann CW, Poyner EA | journal = ] | volume = 51 | pages = 328–337 | year = 1995 | issue = 3 | doi = 10.1107/S0108768194011407 | bibcode = 1995AcCrB..51..328H | s2cid = 96802274 }}</ref>
	<!--Clinical data-->		<!-- Clinical data -->
			| pronounce = {{IPAc-en|ˌ|ɛ|l|ˈ|d|oʊ|p|ə}}, {{IPAc-en|ˌ|l|ɛ|v|oʊ|ˈ|d|oʊ|p|ə}}
	| tradename =
			| tradename = Larodopa, Dopar, Inbrija, others
			| Drugs.com = {{drugs.com|ppa|levodopa-oral-inhalation}}
			| MedlinePlus = a619018
			| licence_EU = yes
			| DailyMedID = Levodopa
			| licence_US = <!-- FDA may use generic or brand name (generic name preferred) -->
	| pregnancy_AU = B3		| pregnancy_AU = B3
			| pregnancy_AU_comment = <ref name="Drugs.com pregnancy">{{cite web | title=Levodopa Use During Pregnancy | website=Drugs.com | date=12 July 2019 | url=https://www.drugs.com/pregnancy/levodopa.html | access-date=27 September 2020}}</ref>
	| pregnancy_US = C
	| legal_status = OTC		| pregnancy_US = N
			| pregnancy_US_comment = <ref name="Drugs.com pregnancy" />
	| routes_of_administration = oral
			| routes_of_administration = ], ], ] (]), ] (as ])
			| class = ]; ]
			| ATC_prefix = N04
			| ATC_suffix = BA01
			<!-- Legal status -->
			| legal_AU = S4
			| legal_AU_comment =
			| legal_BR = <!-- OTC, A1, A2, A3, B1, B2, C1, C2, C3, C4, C5, D1, D2, E, F -->
			| legal_BR_comment =
			| legal_CA = <!-- OTC, Rx-only, Schedule I, II, III, IV, V, VI, VII, VIII -->
			| legal_CA_comment =
			| legal_DE = <!-- Anlage I, II, III or Unscheduled -->
			| legal_DE_comment =
			| legal_NZ = <!-- Class A, B, C -->
			| legal_NZ_comment =
			| legal_UK = POM
			| legal_UK_comment =
			| legal_US = Rx-only
			| legal_US_comment = (some forms are OTC)
			| legal_EU = Rx-only
			| legal_EU_comment =
			| legal_UN = <!-- N I, II, III, IV / P I, II, III, IV -->
			| legal_UN_comment =
			| legal_status = <!-- For countries not listed above -->
	<!--Pharmacokinetic data-->		<!-- Pharmacokinetic data -->
	| bioavailability = 30%		| bioavailability = 30%
			| protein_bound =
	| metabolism = ]
			| metabolism = ]
	| elimination_half-life = 0.75–1.5 hours
	| excretion = ] 70–80%		| metabolites = • ]
			| elimination_half-life = 0.75–1.5 hours
			| excretion = ] 70–80%
	<!--Identifiers-->		<!-- Identifiers -->
	| CASNo_Ref = {{cascite|correct|CAS}}
	| CAS_number_Ref = {{cascite|correct|??}}		| CAS_number_Ref = {{cascite|correct|??}}
	| CAS_number = 59-92-7		| CAS_number = 59-92-7
	| ATC_prefix = N04
	| ATC_suffix = BA01
	| PubChem = 6047		| PubChem = 6047
			| IUPHAR_ligand = 3639
	| DrugBank_Ref = {{drugbankcite|correct|drugbank}}		| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
	| DrugBank = DB01235		| DrugBank = DB01235
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	| KEGG_Ref = {{keggcite|correct|kegg}}		| KEGG_Ref = {{keggcite|correct|kegg}}
	| KEGG = D00059		| KEGG = D00059
	| ChEBI_Ref = {{ebicite|changed|EBI}}		| ChEBI_Ref = {{ebicite|correct|EBI}}
	| ChEBI = 15765		| ChEBI = 15765
	| ChEMBL_Ref = {{ebicite|correct|EBI}}		| ChEMBL_Ref = {{ebicite|correct|EBI}}
	| ChEMBL = 1009		| ChEMBL = 1009
			| synonyms = <small>L</small>-DOPA
	<!--Chemical data-->		<!-- Chemical data -->
	| C=9 | H=11 | N=1 | O=4		| C=9 | H=11 | N=1 | O=4
			| SMILES = O=C(O)(N)Cc1cc(O)c(O)cc1
	| molecular_weight = 197.19 g/mol
	| smiles = O=C(O)(N)Cc1cc(O)c(O)cc1
	| StdInChI_Ref = {{stdinchicite|correct|chemspider}}		| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
	| StdInChI = 1S/C9H11NO4/c10-6(9(13)14)3-5-1-2-7(11)8(12)4-5/h1-2,4,6,11-12H,3,10H2,(H,13,14)/t6-/m0/s1		| StdInChI = 1S/C9H11NO4/c10-6(9(13)14)3-5-1-2-7(11)8(12)4-5/h1-2,4,6,11-12H,3,10H2,(H,13,14)/t6-/m0/s1
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	| StdInChIKey = WTDRDQBEARUVNC-LURJTMIESA-N		| StdInChIKey = WTDRDQBEARUVNC-LURJTMIESA-N
	}}		}}
			<!-- Definition and medical uses -->
			'''Levodopa''', also known as '''<small>L</small>-DOPA''' and sold under many brand names, is a ] ] which is used in the treatment of ] and certain other conditions like ] and ].<ref name="WhitfieldMooreDaniels2014">{{cite journal | vauthors = Whitfield AC, Moore BT, Daniels RN | title = Classics in chemical neuroscience: levodopa | journal = ACS Chem Neurosci | volume = 5 | issue = 12 | pages = 1192–1197 | date = December 2014 | pmid = 25270271 | doi = 10.1021/cn5001759 | url = }}</ref> The drug is usually used and formulated in combination with a ] ] (AAAD) ] like ] or ].<ref name="WhitfieldMooreDaniels2014" /> Levodopa is taken ], ], ], or by ] (as ]).<ref name="WhitfieldMooreDaniels2014" />
			<!-- Side effects, mechanism of action, and chemistry -->
			]s of levodopa include ], the wearing-off phenomenon, ], and ], among others.<ref name="WhitfieldMooreDaniels2014" /> The drug is a ] ] ] and ] of ] and hence acts as a ].<ref name="WhitfieldMooreDaniels2014" /> Chemically, levodopa is an ], a ], and a ].<ref name="WhitfieldMooreDaniels2014" />
			<!-- History, society, and culture -->
			Levodopa was first ] and isolated in the early 1910s.<ref name="WhitfieldMooreDaniels2014" /> The ] effects of levodopa were discovered in the 1950s and 1960s.<ref name="WhitfieldMooreDaniels2014" /> Following this, it was introduced for the treatment of Parkinson's disease in 1970.<ref name="WhitfieldMooreDaniels2014" />
			==Medical uses==
			Levodopa crosses the protective ], whereas ] itself cannot.<ref name="WhitfieldMooreDaniels2014" /><ref>{{cite journal | vauthors = Hardebo JE, Owman C | title = Barrier mechanisms for neurotransmitter monoamines and their precursors at the blood-brain interface | journal = Annals of Neurology | volume = 8 | issue = 1 | pages = 1–31 | date = July 1980 | pmid = 6105837 | doi = 10.1002/ana.410080102 | s2cid = 22874032 }}</ref> Thus, levodopa is used to increase dopamine concentrations in the treatment of ], ], ] and ]. The therapeutic efficacy is different for different kinds of symptoms. ] and ] are the most responsive symptoms while ]s are less responsive to levodopa therapy. Speech, ], postural instability, and freezing gait are the least responsive symptoms.<ref name=":0">{{cite journal | vauthors = Ovallath S, Sulthana B | title = Levodopa: History and Therapeutic Applications | journal = Annals of Indian Academy of Neurology | volume = 20 | issue = 3 | pages = 185–189 | date = 2017 | pmid = 28904446 | pmc = 5586109 | doi = 10.4103/aian.AIAN_241_17 | doi-access = free }}</ref>
			Once levodopa has entered the ], it is converted into dopamine by the ] ] (AAAD), also known as ] (DDC). ] (]) is a required ] in this ], and may occasionally be administered along with levodopa, usually in the ] of ]. Because levodopa bypasses the enzyme ], the rate-limiting step in dopamine synthesis, it is much more readily converted to dopamine than tyrosine, which is normally the natural precursor for dopamine production.
			In humans, conversion of levodopa to dopamine does not only occur within the ]. Cells in the ] perform the same task. Thus administering levodopa alone will lead to increased dopamine signaling in the periphery as well. Excessive peripheral dopamine signaling is undesirable as it causes many of the adverse ]s seen with sole levodopa administration. To bypass these effects, it is standard clinical practice to coadminister (with levodopa) a peripheral ] (DDCI) such as ] (medicines containing carbidopa, either alone or in combination with levodopa, are branded as ]<ref name="Medicare">{{cite web | url=http://www.q1medicare.com/PartD-2014MedicarePlan-RetailDrugPriceprint.php?stateReg=22Tx&ndc=25010071115&formulary=00014006&contractId=S5660&planId=192&segmentId=0&zipCountyCode=0&cplanType=P&cletter=L&cmode=state | title=Medicare D | publisher=Medicare | date=2014 | access-date=12 November 2015}}</ref> (])<ref name="Aton">{{citation |url=https://www.drugs.com/pro/lodosyn.html |title=Lodosyn |work=Drugs |date=n.d. |access-date=12 November 2012 }}</ref> ] (]), Pharmacopa (]), ] (]), Syndopa and ] (]) or with a ] (combination medicines are branded Madopar or Prolopa), to prevent the peripheral synthesis of dopamine from levodopa). However, when consumed as a botanical extract, for example from ''M pruriens'' supplements, a peripheral ] is not present.<ref name="JAMANeuro">{{cite journal | vauthors = Cohen PA, Avula B, Katragunta K, Khan I | title = Levodopa Content of Mucuna pruriens Supplements in the NIH Dietary Supplement Label Database | journal = JAMA Neurology | volume = 79 | issue = 10 | pages = 1085–1086 | date = October 2022 | pmid = 35939305 | doi = 10.1001/jamaneurol.2022.2184 | pmc = 9361182 }}</ref>
			Inbrija (previously known as CVT-301) is an inhaled powder formulation of levodopa indicated for the intermittent treatment of "off episodes" in patients with Parkinson's disease currently taking ].<ref>{{Cite web|url=https://www.inbrija.com/prescribing-information.pdf|title=Inbrija Prescribing Information |access-date=14 February 2019}}</ref> It was approved by the United States ] on 21 December 2018, and is marketed by ].<ref>{{Cite web|url=http://ir.acorda.com/investors/investor-news/investor-news-details/2018/Acorda-Therapeutics-Announces-FDA-Approval-of-INBRIJA-levodopa-inhalation-powder/default.aspx|title=Acorda Therapeutics Announces FDA Approval of INBRIJA™ (levodopa inhalation powder)|website=ir.acorda.com|language=en-CA|access-date=14 February 2019}}</ref>
			Coadministration of ] without a DDCI accelerates the peripheral ] of levodopa to such an extent that it negates the effects of levodopa administration, a phenomenon that historically caused great confusion.
			In addition, levodopa, co-administered with a peripheral DDCI, is efficacious for the short-term treatment of ].<ref>{{cite journal | vauthors = Scholz H, Trenkwalder C, Kohnen R, Riemann D, Kriston L, Hornyak M | title = Levodopa for restless legs syndrome | journal = The Cochrane Database of Systematic Reviews | issue = 2 | pages = CD005504 | date = February 2011 | volume = 2011 | pmid = 21328278 | doi = 10.1002/14651858.CD005504.pub2 | pmc = 8889887 | collaboration = Cochrane Movement Disorders Group }}</ref>
			The two types of response seen with administration of levodopa are:
			* The short-duration response is related to the half-life of the drug.
			* The longer-duration response depends on the accumulation of effects over at least two weeks, during which ] accumulates in ]. In the treatment of Parkinson's disease, this response is evident only in early therapy, as the inability of the brain to store dopamine is not yet a concern.
			===Available forms===
			Levodopa is available, alone and/or in ] with ], in the form of ] ] ]s and ]s, ] oral tablets and capsules, ]s, as a powder for ], and as an ] ] or ] (via ]).<ref name="LivingstonMonroe-Duprey2024">{{cite journal | vauthors = Livingston C, Monroe-Duprey L | title = A Review of Levodopa Formulations for the Treatment of Parkinson's Disease Available in the United States | journal = J Pharm Pract | volume = 37 | issue = 2 | pages = 485–494 | date = April 2024 | pmid = 36704966 | doi = 10.1177/08971900221151194 | url = }}</ref><ref name="Drugs@FDA">{{cite web | title=Drugs@FDA: FDA-Approved Drugs | website=accessdata.fda.gov | url=https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm | access-date=28 September 2024}}</ref> In terms of combination formulations, it is available with ] (as ]), with ] (as ]), and with both carbidopa and ] (as ]).<ref name="LivingstonMonroe-Duprey2024" /><ref name="Drugs@FDA" /><ref name="IndexNominum2004" /><ref name="Drugs.com-International" /> In addition to levodopa itself, certain ]s of levodopa are available, including ] (]) (used orally) and ] (]) (used ]).<ref name="NakmodeDaySong2023">{{cite journal | vauthors = Nakmode DD, Day CM, Song Y, Garg S | title = The Management of Parkinson's Disease: An Overview of the Current Advancements in Drug Delivery Systems | journal = Pharmaceutics | volume = 15 | issue = 5 | date = May 2023 | page = 1503 | pmid = 37242745 | pmc = 10223383 | doi = 10.3390/pharmaceutics15051503 | doi-access = free | url = }}</ref><ref name="FabbriBarbosaRascol2023">{{cite journal | vauthors = Fabbri M, Barbosa R, Rascol O | title = Off-time Treatment Options for Parkinson's Disease | journal = Neurol Ther | volume = 12 | issue = 2 | pages = 391–424 | date = April 2023 | pmid = 36633762 | pmc = 10043092 | doi = 10.1007/s40120-022-00435-8 | url = }}</ref><ref name="LeesTolosaStocchi2023">{{cite journal | vauthors = Lees A, Tolosa E, Stocchi F, Ferreira JJ, Rascol O, Antonini A, Poewe W | title = Optimizing levodopa therapy, when and how? Perspectives on the importance of delivery and the potential for an early combination approach | journal = Expert Rev Neurother | volume = 23 | issue = 1 | pages = 15–24 | date = January 2023 | pmid = 36729395 | doi = 10.1080/14737175.2023.2176220 | url = | hdl = 10451/56313 | hdl-access = free }}</ref>
			==Side effects==
			The ]s of levodopa may include:
			* ], especially if the dosage is too high
			* ]s, although these are uncommon
			* ], which is often reduced by taking the drug with food, although ] reduces drug absorption. Levodopa is an amino acid, so protein competitively inhibits levodopa absorption.
			* Gastrointestinal bleeding
			* Disturbed ], which is not always harmful, and can actually benefit patients with upper airway obstruction
			* ]
			* ] and ]
			* Extreme ]al states, particularly ], but also excessive ]
			* Vivid ]s or ]
			* ] or ]
			* Effects on learning; some evidence indicates it improves ], while impairing other complex functions
			* ] and ]
			* A condition similar to ]
			Although many adverse effects are associated with levodopa, in particular psychiatric ones, it has fewer than other ]s, such as ]s and ]s.
			More serious are the effects of chronic levodopa administration in the treatment of Parkinson's disease, which include:
			* End-of-dose deterioration of function
			* "On/off" oscillations
			* Freezing during movement
			* Dose failure (])
			* ] at peak dose (])
			* Possible dopamine dysregulation: The long-term use of levodopa in Parkinson's disease has been linked to the so-called ].<ref name="pmid17988927">{{cite journal | vauthors = Merims D, Giladi N | title = Dopamine dysregulation syndrome, addiction and behavioral changes in Parkinson's disease | journal = Parkinsonism & Related Disorders | volume = 14 | issue = 4 | pages = 273–80 | year = 2008 | pmid = 17988927 | doi = 10.1016/j.parkreldis.2007.09.007 }}</ref>
			Rapidly decreasing the dose of levodopa can result in ].
			Clinicians try to avoid these side effects and adverse reactions by limiting levodopa doses as much as possible until absolutely necessary.
			Metabolites of dopamine, such as ], are known to be ]s. The long term use of levodopa increases oxidative stress through ] led enzymatic degradation of synthesized dopamine causing neuronal damage and cytotoxicity. The oxidative stress is caused by the formation of ] (H<sub>2</sub>O<sub>2</sub>) during the monoamine oxidase led metabolism of dopamine. It is further perpetuated by the richness of Fe<sup>2+</sup> ions in striatum via the Fenton reaction and intracellular ]. The increased oxidation can potentially cause mutations in DNA due to the formation of ], which is capable of pairing with adenosine during ].<ref>{{cite journal | vauthors = Dorszewska J, Prendecki M, Lianeri M, Kozubski W | title = Molecular Effects of L-dopa Therapy in Parkinson's Disease | journal = Current Genomics | volume = 15 | issue = 1 | pages = 11–7 | date = February 2014 | pmid = 24653659 | pmc = 3958954 | doi = 10.2174/1389202914666131210213042 }}</ref> See also the ].
			==Pharmacology==
			===Pharmacodynamics===
			Levodopa is a ] and ] of ] and hence acts as a ] ], including of the ]s (], ]) and the ]s (], ], ]).<ref name="WhitfieldMooreDaniels2014" />
			===Pharmacokinetics===
			The ] of levodopa is 30%.<ref name="WhitfieldMooreDaniels2014" /> It is ] into ] by ] (AAAD) in the ] and periphery.<ref name="WhitfieldMooreDaniels2014" /> The ] of levodopa is 0.75 to 1.5{{nbsp}}hours.<ref name="WhitfieldMooreDaniels2014" /> It is ] 70–80% in ].
			==Chemistry==
			Levodopa is an ] and a ] and ].<ref name="WhitfieldMooreDaniels2014" />
			]s and prodrugs of levodopa include ], ], ], and ]. Some of these, like melevodopa and foslevodopa, are approved for the treatment of ] similarly to levodopa.
			Other analogues include ], an ], and ] (<small>L</small>-DOPS), a ] and prodrug.
			], a prodrug of ] (6-OHDA), is a ] ] used in ].
			==History==
			Levodopa was first ] in 1911 by Torquato Torquati from the '']'' bean.<ref name="WhitfieldMooreDaniels2014" /> It was first isolated in 1913 by Marcus Guggenheim from the ''V.{{nbsp}}faba'' bean.<ref name="WhitfieldMooreDaniels2014" /> Guggenheim tried levodopa at a dose of 2.5{{nbsp}}mg and thought that it was inactive aside from ] and ].<ref name="WhitfieldMooreDaniels2014" />
			In work that earned him a ] in 2000, ] scientist ] first showed in the 1950s that administering levodopa to animals with drug-induced (]) Parkinsonian ]s caused a reduction in the intensity of the animals' symptoms. In 1960 or 1961 ], after discovering greatly reduced levels of dopamine in autopsied brains of patients with Parkinson's disease,<ref name="WhitfieldMooreDaniels2014" /><ref name="pmid13726012">{{cite journal | vauthors = Ehringer H, Hornykiewicz O | title = | journal = Klinische Wochenschrift | volume = 38 | issue = 24 | pages = 1236–9 | date = December 1960 | pmid = 13726012 | doi = 10.1007/BF01485901 | s2cid = 32896604 }}</ref> published together with the neurologist Walther Birkmayer dramatic therapeutic antiparkinson effects of intravenously administered levodopa in patients.<ref name="pmid13869404">{{cite journal | vauthors = Birkmayer W, Hornykiewicz O | title = | journal = Wiener Klinische Wochenschrift | volume = 73 | pages = 787–8 | date = November 1961 | pmid = 13869404 }}</ref> This treatment was later extended to manganese poisoning and later Parkinsonism by ] and his coworkers,<ref>{{cite journal | vauthors = Cotzias GC, Papavasiliou PS, Gellene R | title = L-dopa in parkinson's syndrome | journal = The New England Journal of Medicine | volume = 281 | issue = 5 | pages = 272 | date = July 1969 | pmid = 5791298 | doi = 10.1056/NEJM196907312810518 }}</ref> who used greatly increased oral doses, for which they won the 1969 ].<ref>{{cite web | url = http://www.laskerfoundation.org/awards/1969_c_description.htm | title = Lasker Award | date = 1969 | archive-url = https://web.archive.org/web/20160105102139/http://www.laskerfoundation.org/awards/1969_c_description.htm| archive-date= 5 January 2016}}, retrieved 1 April 2013</ref><ref>{{cite book | vauthors = Simuni T, Hurtig H | chapter = Levadopa: A Pharmacologic Miracle Four Decades Later | url = https://books.google.com/books?id=zUp54Dm-Y7MC | title = Parkinson's Disease: Diagnosis and Clinical Management | via = Google eBook | veditors = Factor SA, Weiner WJ | publisher = Demos Medical Publishing | date = 2008 | isbn = 978-1-934559-87-1 }}</ref> The first study reporting improvements in patients with Parkinson's disease resulting from treatment with levodopa was published in 1968.<ref name="pmid5637779">{{cite journal | vauthors = Cotzias GC | title = L-Dopa for Parkinsonism | journal = The New England Journal of Medicine | volume = 278 | issue = 11 | pages = 630 | date = March 1968 | pmid = 5637779 | doi = 10.1056/nejm196803142781127 }}</ref>
			Levodopa was first marketed in 1970 by Roche under the brand name Larodopa.<ref name="WhitfieldMooreDaniels2014" />
			The ] ] describes this treatment in human patients with ] in his 1973 book '']'', upon which ] is based.
			] was added to levodopa in 1974 and this improved its ].<ref name="WhitfieldMooreDaniels2014" />
			==Society and culture==
			===Names===
			''Levodopa'' is the ] of the drug and its {{Abbrlink|INN|International Nonproprietary Name}}, {{Abbrlink|USAN|United States Adopted Name}}, {{Abbrlink|USP|United States Pharmacopeia}}, {{Abbrlink|BAN|British Approved Name}}, {{Abbrlink|DCF|Dénomination Commune Française}}, {{Abbrlink|DCIT|Denominazione Comune Italiana}}, and {{Abbrlink|JAN|Japanese Accepted Name}}.<ref name="Elks2014">{{cite book | vauthors = Elks J | title=The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies | publisher=Springer US | year=2014 | isbn=978-1-4757-2085-3 | url=https://books.google.com/books?id=0vXTBwAAQBAJ&pg=PA54 | access-date=28 September 2024 | page=54}}</ref><ref name="MortonHall2012">{{cite book | vauthors = Morton IK, Hall JM | title=Concise Dictionary of Pharmacological Agents: Properties and Synonyms | publisher=Springer Netherlands | year=2012 | isbn=978-94-011-4439-1 | url=https://books.google.com/books?id=tsjrCAAAQBAJ&pg=PA164 | access-date=28 September 2024 | page=164}}</ref><ref name="IndexNominum2004">{{cite book | author=Schweizerischer Apotheker-Verein | title=Index Nominum: International Drug Directory | publisher=Medpharm Scientific Publishers | year=2004 | isbn=978-3-88763-101-7 | url=https://books.google.com/books?id=EgeuA47Ocm4C&pg=PA699 | access-date=28 September 2024 | page=699}}</ref><ref name="Drugs.com-International">{{cite web | title=Levodopa (International database) | website=Drugs.com | date=2 September 2024 | url=https://www.drugs.com/international/levodopa.html | access-date=28 September 2024}}</ref>
			==Research==
			===Novel formulations and prodrugs===
			New levodopa formulations for use by other ], such as ], are being developed.<ref name="Doggrell2023">{{cite journal | vauthors = Doggrell SA | title = Continuous subcutaneous levodopa-carbidopa for the treatment of advanced Parkinson's disease: is it an improvement on other delivery? | journal = Expert Opin Drug Deliv | volume = 20 | issue = 9 | pages = 1189–1199 | date = 2023 | pmid = 37634938 | doi = 10.1080/17425247.2023.2253146 | url = }}</ref><ref name="UrsoChaudhuriQamar2020">{{cite journal | vauthors = Urso D, Chaudhuri KR, Qamar MA, Jenner P | title = Improving the Delivery of Levodopa in Parkinson's Disease: A Review of Approved and Emerging Therapies | journal = CNS Drugs | volume = 34 | issue = 11 | pages = 1149–1163 | date = November 2020 | pmid = 33146817 | doi = 10.1007/s40263-020-00769-7 | url = }}</ref>
			Levodopa ]s, with the potential for better ], reduced fluctuations in levodopa levels, and reduced "on–off" phenomenon, are being researched and developed.<ref name="CacciatoreCiullaMarinelli2018">{{cite journal | vauthors = Cacciatore I, Ciulla M, Marinelli L, Eusepi P, Di Stefano A | title = Advances in prodrug design for Parkinson's disease | journal = Expert Opin Drug Discov | volume = 13 | issue = 4 | pages = 295–305 | date = April 2018 | pmid = 29361853| doi = 10.1080/17460441.2018.1429400 | url = }}</ref><ref name="HaddadSawalhaKhawaja2017">{{cite journal | vauthors = Haddad F, Sawalha M, Khawaja Y, Najjar A, Karaman R | title = Dopamine and Levodopa Prodrugs for the Treatment of Parkinson's Disease | journal = Molecules | volume = 23 | issue = 1 | date = December 2017 | page = 40 | pmid = 29295587 | pmc = 5943940 | doi = 10.3390/molecules23010040 | doi-access = free | url = }}</ref>
			===Depression===
			Levodopa has been reported to be inconsistently effective as an ] in the treatment of ]s.<ref name="SalamoneYohnLópez-Cruz2016">{{cite journal | vauthors = Salamone JD, Yohn SE, López-Cruz L, San Miguel N, Correa M | title = Activational and effort-related aspects of motivation: neural mechanisms and implications for psychopathology | journal = Brain | volume = 139 | issue = Pt 5 | pages = 1325–1347 | date = May 2016 | pmid = 27189581 | pmc = 5839596 | doi = 10.1093/brain/aww050 | url = }}</ref><ref name="BrownGershon1993">{{cite journal | vauthors = Brown AS, Gershon S | title = Dopamine and depression | journal = J Neural Transm Gen Sect | volume = 91 | issue = 2–3 | pages = 75–109 | date = 1993 | pmid = 8099801 | doi = 10.1007/BF01245227 | url = }}</ref> However, it was found to enhance psychomotor activation in people with depression.<ref name="SalamoneYohnLópez-Cruz2016" /><ref name="BrownGershon1993" />
			===Motivational disorders===
			Levodopa has been found to increase the willingness to exert ] for ]s in humans and hence appears to show ] effects.<ref name="WebberLopez-GamundiStamatovich2021">{{cite journal | vauthors = Webber HE, Lopez-Gamundi P, Stamatovich SN, de Wit H, Wardle MC | title = Using pharmacological manipulations to study the role of dopamine in human reward functioning: A review of studies in healthy adults | journal = Neurosci Biobehav Rev | volume = 120 | issue = | pages = 123–158 | date = January 2021 | pmid = 33202256 | pmc = 7855845 | doi = 10.1016/j.neubiorev.2020.11.004 | url = }}</ref><ref name="ZénonDevesseOlivier2016">{{cite journal | vauthors = Zénon A, Devesse S, Olivier E | title = Dopamine Manipulation Affects Response Vigor Independently of Opportunity Cost | journal = J Neurosci | volume = 36 | issue = 37 | pages = 9516–9525 | date = September 2016 | pmid = 27629704 | pmc = 6601940 | doi = 10.1523/JNEUROSCI.4467-15.2016 | url = }}</ref> Other ]s have also shown pro-motivational effects and may be useful in the treatment of ]s.<ref name="SalamoneCorrea2024">{{cite journal | vauthors = Salamone JD, Correa M | title = The Neurobiology of Activational Aspects of Motivation: Exertion of Effort, Effort-Based Decision Making, and the Role of Dopamine | journal = Annu Rev Psychol | volume = 75 | issue = | pages = 1–32 | date = January 2024 | pmid = 37788571 | doi = 10.1146/annurev-psych-020223-012208 | url = | hdl = 10234/207207 | hdl-access = free }}</ref>
			===Age-related macular degeneration===
			In 2015, a retrospective analysis comparing the incidence of ] (AMD) between patients taking versus not taking levodopa found that the drug delayed onset of AMD by around 8{{nbsp}}years. The authors state that significant effects were obtained for both dry and wet AMD.<ref>{{cite journal | vauthors = Brilliant MH, Vaziri K, Connor TB, Schwartz SG, Carroll JJ, McCarty CA, Schrodi SJ, Hebbring SJ, Kishor KS, Flynn HW, Moshfeghi AA, Moshfeghi DM, Fini ME, McKay BS | title = Mining Retrospective Data for Virtual Prospective Drug Repurposing: L-DOPA and Age-related Macular Degeneration | journal = The American Journal of Medicine | volume = 129 | issue = 3 | pages = 292–8 | date = March 2016 | pmid = 26524704 | pmc = 4841631 | doi = 10.1016/j.amjmed.2015.10.015 }}</ref>{{Primary source inline|date=December 2016}}
			==References==
			{{Reflist}}
			==External links==
			* {{cite web | url = https://druginfo.nlm.nih.gov/drugportal/name/levodopa | publisher = U.S. National Library of Medicine | work = Drug Information Portal | title = Levodopa }}
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