Wikipedia:WikiProject Chemicals/Chembox validation/VerifiedDataSandbox and L-DOPA: Difference between pages

{{short description|Chemical compound}}

{{cs1 config|name-list-style=vanc|display-authors=6}}

{{DISPLAYTITLE:<small>L</small>-DOPA}}

{{Infobox drug

| Watchedfields = changed

| verifiedrevid = 461087196

| IUPAC_name = (''S'')-2-Amino-3-(3,4-dihydroxyphenyl)propanoic acid

| caption = [[Skeletal formula]] of <small>L</small>-DOPA

| image2 = L-DOPA-from-xtal-view-2-3D-bs-17.png

| width2 = 180px

| caption2 = [[Ball-and-stick model]] of the [[zwitterion]]ic form of <small>L</small>-DOPA found in the [[crystal structure]]<ref>{{ cite journal | title = Experimental and theoretical determination of electronic properties in Ldopa | vauthors = Howard ST, Hursthouse MB, Lehmann CW, Poyner EA | journal = [[Acta Crystallographica|Acta Crystallogr. B]] | volume = 51 | pages = 328–337 | year = 1995 | issue = 3 | doi = 10.1107/S0108768194011407 | bibcode = 1995AcCrB..51..328H | s2cid = 96802274 }}</ref>

| drug_name = {{sm|l}}-DOPA

| pronounce = {{IPAc-en|ˌ|ɛ|l|ˈ|d|oʊ|p|ə}}, {{IPAc-en|ˌ|l|ɛ|v|oʊ|ˈ|d|oʊ|p|ə}}

| 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_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 = N

| pregnancy_US_comment = <ref name="Drugs.com pregnancy" />

| routes_of_administration = [[Oral administration|By mouth]], [[intravenous]]

| 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 -->

| metabolism = [[Aromatic-L-amino-acid decarboxylase|Aromatic-{{sm|l}}-amino-acid decarboxylase]]

| elimination_half-life = 0.75–1.5 hours

| excretion = [[renal]] 70–80%

| IUPHAR_ligand = 3639

| ChEBI_Ref = {{ebicite|correct|EBI}}

| C=9 | H=11 | N=1 | O=4

'''{{sm|l}}-DOPA''', also known as '''levodopa''' and '''{{sm|l}}-3,4-dihydroxyphenylalanine''', is made and used as part of the normal [[biology]] of some plants <ref name="JAMANeuro" /> and animals, including humans. Humans, as well as a portion of the other animals that utilize {{sm|l}}-DOPA, make it via [[biosynthesis]] from the [[amino acid]] [[L-tyrosine|{{sm|l}}-tyrosine]]. {{sm|l}}-DOPA is the [[precursor (chemistry)|precursor]] to the [[neurotransmitter]]s [[dopamine]], [[norepinephrine]] (noradrenaline), and [[epinephrine]] (adrenaline), which are collectively known as [[catecholamine]]s. Furthermore, {{sm|l}}-DOPA itself mediates [[Neurotrophic factors|neurotrophic factor]] release by the brain and CNS.<ref>{{cite journal | vauthors = Lopez VM, Decatur CL, Stamer WD, Lynch RM, McKay BS | title = L-DOPA is an endogenous ligand for OA1 | journal = PLOS Biology | volume = 6 | issue = 9 | pages = e236 | date = September 2008 | pmid = 18828673 | pmc = 2553842 | doi = 10.1371/journal.pbio.0060236 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Hiroshima Y, Miyamoto H, Nakamura F, Masukawa D, Yamamoto T, Muraoka H, Kamiya M, Yamashita N, Suzuki T, Matsuzaki S, Endo I, Goshima Y | title = The protein Ocular albinism 1 is the orphan GPCR GPR143 and mediates depressor and bradycardic responses to DOPA in the nucleus tractus solitarii | journal = British Journal of Pharmacology | volume = 171 | issue = 2 | pages = 403–14 | date = January 2014 | pmid = 24117106 | pmc = 3904260 | doi = 10.1111/bph.12459 }}</ref> In some plant families (of the order [[Caryophyllales]]), {{sm|l}}-DOPA is the central precursor of a biosynthetic pathway that produces a class of pigments called [[betalain]]s.<ref>{{cite journal |vauthors= Polturak G, Breitel D, Grossman N, Sarrion-Perdigones A, Weithorn E, Pliner M, Orzaez D, Granell A, Rogachev I, Aharoni A |title=Elucidation of the first committed step in betalain biosynthesis enables the heterologous engineering of betalain pigments in plants |journal= New Phytol |volume=210 |issue=1 |pages= 269–283 |year=2016 |doi=10.1111/nph.13796 |doi-access=free |pmid=26683006 }}</ref> {{sm|l}}-DOPA can be manufactured and in its pure form is sold as a [[psychoactive drug]] with the [[International Nonproprietary Name|INN]] levodopa; trade names include Sinemet, Pharmacopa, Atamet, and Stalevo. As a drug, it is used in the clinical [[therapy|treatment]] of [[Parkinson's disease]] and [[dopamine-responsive dystonia]].

{{sm|l}}-DOPA has a counterpart with opposite [[chirality (chemistry)#By configuration: D- and L-|chirality]], [[D-DOPA|{{sm|d}}-DOPA]]. As is true for many molecules, the human body produces only one of these [[isomer]]s (the {{sm|l}}-DOPA form). The [[Enantiomer|enantiomeric purity]] of {{sm|l}}-DOPA may be analyzed by determination of the optical rotation or by chiral [[thin-layer chromatography]].<ref>{{cite journal | vauthors = Martens J, Günther K, Schickedanz M | title = Resolution of Optical Isomers by Thin-Layer Chromatography: Enantiomeric Purity of Methyldopa | journal = [[Arch. Pharm.]] | volume = 319 | issue = 6 | pages = 572–574 | date = 1986 | doi = 10.1002/ardp.19863190618 | s2cid = 97903386 }}</ref>

==Medical use==

{{sm|l}}-DOPA crosses the protective [[blood–brain barrier]], whereas [[dopamine]] itself cannot.<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, {{sm|l}}-DOPA is used to increase dopamine concentrations in the treatment of [[Parkinson's disease]], [[Parkinsonism]], [[dopamine-responsive dystonia]] and [[Parkinson-plus syndrome]]. The therapeutic efficacy is different for different kinds of symptoms. [[Hypokinesia|Bradykinesia]] and [[Rigidity (neurology)|rigidity]] are the most responsive symptoms while [[tremor]]s are less responsive to levodopa therapy. Speech, [[Dysphagia|swallowing disorders]], 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 {{sm|l}}-DOPA has entered the [[central nervous system]], it is converted into dopamine by the [[enzyme]] [[aromatic L-amino acid decarboxylase|aromatic {{sm|l}}-amino acid decarboxylase]], also known as [[DOPA decarboxylase]]. [[Pyridoxal phosphate]] ([[Vitamin B6|vitamin B₆]]) is a required [[cofactor (biochemistry)|cofactor]] in this [[chemical reaction|reaction]], and may occasionally be administered along with {{sm|l}}-DOPA, usually in the [[drug form|form]] of [[pyridoxine]]. Because levodopa bypasses the enzyme [[tyrosine hydroxylase]], 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 {{sm|l}}-DOPA to dopamine does not only occur within the [[central nervous system]]. Cells in the [[peripheral nervous system]] perform the same task. Thus administering {{sm|l}}-DOPA 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 [[adverse effect|side effect]]s seen with sole <small>L</small>-DOPA administration. To bypass these effects, it is standard clinical practice to coadminister (with {{sm|l}}-DOPA) a peripheral [[DOPA decarboxylase inhibitor]] (DDCI) such as [[carbidopa]] (medicines containing carbidopa, either alone or in combination with {{sm|l}}-DOPA, are branded as [[Carbidopa|Lodosyn]]<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> ([[Valeant Pharmaceuticals|Aton Pharma]])<ref name="Aton">{{citation |url=https://www.drugs.com/pro/lodosyn.html |title=Lodosyn |work=Drugs |date=nd |access-date=12 November 2012 }}</ref> [[Carbidopa/levodopa|Sinemet]] ([[Merck & Co.|Merck Sharp & Dohme Limited]]), Pharmacopa ([[Jazz Pharmaceuticals]]), [[Carbidopa/levodopa|Atamet]] ([[UCB (company)|UCB]]), Syndopa and [[Carbidopa/levodopa/entacapone|Stalevo]] ([[Orion Corporation (pharmaceutical company)|Orion Corporation]]) or with a [[benserazide]] (combination medicines are branded Madopar or Prolopa), to prevent the peripheral synthesis of dopamine from {{sm|l}}-DOPA). However, when consumed as a botanical extract, for example from ''M pruriens'' supplements, a peripheral [[DOPA decarboxylase inhibitor]] 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 [[carbidopa/levodopa]].<ref>{{Cite web|url=https://www.inbrija.com/prescribing-information.pdf|title=Inbrija Prescribing Information |access-date=February 14, 2019}}</ref> It was approved by the United States [[Food and Drug Administration]] on December 21, 2018, and is marketed by [[Acorda Therapeutics]].<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=2019-02-14}}</ref>

Coadministration of [[pyridoxine]] without a DDCI accelerates the peripheral [[decarboxylation]] of {{sm|l}}-DOPA to such an extent that it negates the effects of {{sm|l}}-DOPA administration, a phenomenon that historically caused great confusion.

In addition, {{sm|l}}-DOPA, co-administered with a peripheral DDCI, is efficacious for the short-term treatment of [[restless leg syndrome]].<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 {{sm|l}}-DOPA 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 [[ΔFosB]] accumulates in [[nigrostriatal pathway|nigrostriatal neurons]]. 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.

==Biological role==

{{phenylalanine biosynthesis|align=right}}

{{sm|l}}-DOPA is produced from the amino acid {{sm|l}}-[[tyrosine]] by the enzyme [[tyrosine hydroxylase]]. {{sm|l}}-DOPA can act as an {{sm|l}}-tyrosine mimetic and be incorporated into proteins by mammalian cells in place of L-tyrosine, generating [[protease]]-resistant and [[protein aggregation|aggregate-prone proteins]] ''in vitro'' and may contribute to [[neurotoxicity]] with chronic {{sm|l}}-DOPA administration.<ref>{{cite journal | vauthors = Rodgers KJ | title = Non-protein amino acids and neurodegeneration: the enemy within | journal = Experimental Neurology | volume = 253 | pages = 192–196 | date = March 2014 | pmid = 24374297 | doi = 10.1016/j.expneurol.2013.12.010 | s2cid = 2288729 }}</ref>

It is also the precursor for the [[monoamine]] or [[catecholamine]] neurotransmitters dopamine, norepinephrine (noradrenaline), and epinephrine (adrenaline). Dopamine is formed by the decarboxylation of {{sm|l}}-DOPA by [[aromatic L-amino acid decarboxylase|aromatic {{sm|l}}-amino acid decarboxylase]] (AADC).

{{sm|l}}-DOPA can be directly metabolized by [[catechol-O-methyl transferase|catechol-''O''-methyl transferase]] to [[3-O-methyldopa|3-''O''-methyldopa]], and then further to [[vanillactic acid]]. This metabolic pathway is nonexistent in the healthy body, but becomes important after peripheral {{sm|l}}-DOPA administration in patients with Parkinson's disease or in the rare cases of patients with AADC enzyme deficiency.<ref name="pmid1281049">{{cite journal | vauthors = Hyland K, Clayton PT | title = Aromatic L-amino acid decarboxylase deficiency: diagnostic methodology | journal = Clinical Chemistry | volume = 38 | issue = 12 | pages = 2405–10 | date = December 1992 | pmid = 1281049 | doi = 10.1093/clinchem/38.12.2405| url = http://www.clinchem.org/cgi/reprint/38/12/2405.pdf | access-date = 2008-10-16 | archive-url = https://web.archive.org/web/20110607122144/http://www.clinchem.org/cgi/reprint/38/12/2405.pdf | archive-date = 2011-06-07 | url-status = dead | doi-access = free }}</ref>

{{sm|l}}-Phenylalanine, {{sm|l}}-tyrosine, and {{sm|l}}-DOPA are all precursors to the biological [[pigment]] [[melanin]]. The enzyme [[tyrosinase]] [[catalyst|catalyzes]] the [[oxidation]] of {{sm|l}}-DOPA to the reactive intermediate [[dopaquinone]], which reacts further, eventually leading to melanin [[oligomer]]s. In addition, [[tyrosinase]] can convert tyrosine directly to {{sm|l}}-DOPA in the presence of a reducing agent such as [[ascorbic acid]].<ref>{{cite journal | vauthors = Ito S, Kato T, Shinpo K, Fujita K | title = Oxidation of tyrosine residues in proteins by tyrosinase. Formation of protein-bonded 3,4-dihydroxyphenylalanine and 5-S-cysteinyl-3,4-dihydroxyphenylalanine | journal = The Biochemical Journal | volume = 222 | issue = 2 | pages = 407–11 | date = September 1984 | pmid = 6433900 | pmc = 1144193 | doi = 10.1042/bj2220407 }}</ref>

==Marine adhesion==

{{sm|l}}-DOPA is a key [[chemical compound|compound]] in the formation of [[marine adhesive protein]]s, such as those found in [[mussel]]s.<ref>{{cite journal | vauthors = Waite JH, Andersen NH, Jewhurst S, Sun C | title=Mussel Adhesion: Finding the Tricks Worth Mimicking | journal=J Adhesion | volume=81 | year=2005 | pages=1–21 | doi=10.1080/00218460590944602 | issue=3–4 | s2cid=136967853 }}</ref><ref>{{cite web | url = https://www.sciencedaily.com/releases/2006/08/060816024159.htm | title = Study Reveals Details Of Mussels' Tenacious Bonds | publisher = Science Daily | date = Aug 16, 2006 | access-date = Sep 30, 2013}}</ref> It is believed to be responsible for the water-resistance and rapid curing abilities of these proteins. {{sm|l}}-DOPA may also be used to prevent surfaces from fouling by bonding antifouling polymers to a susceptible [[substrate (biochemistry)|substrate]].<ref>{{cite web | url = http://biomaterials.bme.northwestern.edu/mussel.asp | title = Mussel Adhesive Protein Mimetics | archive-url = https://web.archive.org/web/20060529181142/http://biomaterials.bme.northwestern.edu/mussel.asp | archive-date=2006-05-29 }}</ref> The versatile chemistry of L-DOPA can be exploited in nanotechnology.<ref>{{cite journal | vauthors = Giuri D, Ravarino P, Tomasini C | title = L-Dopa in small peptides: an amazing functionality to form supramolecular materials | journal = Organic & Biomolecular Chemistry | volume = 19 | issue = 21 | pages = 4622–4636 | date = June 2021 | pmid = 33978030 | doi = 10.1039/D1OB00378J | s2cid = 234474122 | hdl = 11585/840774 | hdl-access = free }}</ref> For example, DOPA-containing self-assembling peptides were found to form functional nanostructures, adhesives and gels.<ref>{{cite journal | vauthors = Fichman G, Adler-Abramovich L, Manohar S, Mironi-Harpaz I, Guterman T, Seliktar D, Messersmith PB, Gazit E | title = Seamless metallic coating and surface adhesion of self-assembled bioinspired nanostructures based on di-(3,4-dihydroxy-L-phenylalanine) peptide motif | journal = ACS Nano | volume = 8 | issue = 7 | pages = 7220–7228 | date = July 2014 | pmid = 24936704 | pmc = 4108209 | doi = 10.1021/nn502240r }}</ref><ref>{{cite journal | vauthors = Fichman G, Guterman T, Adler-Abramovich L, Gazit E | title = The Use of the Calcitonin Minimal Recognition Module for the Design of DOPA-Containing Fibrillar Assemblies | journal = Nanomaterials | volume = 4 | issue = 3 | pages = 726–740 | date = August 2014 | pmid = 28344244 | pmc = 5304689 | doi = 10.3390/nano4030726 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Fichman G, Andrews C, Patel NL, Schneider JP | title = Antibacterial Gel Coatings Inspired by the Cryptic Function of a Mussel Byssal Peptide | journal = Advanced Materials | volume = 33 | issue = 40 | pages = e2103677 | date = October 2021 | pmid = 34423482 | pmc = 8492546 | doi = 10.1002/adma.202103677 | bibcode = 2021AdM....3303677F }}</ref><ref>{{cite journal | vauthors = Maity S, Nir S, Zada T, Reches M | title = Self-assembly of a tripeptide into a functional coating that resists fouling | journal = Chemical Communications | volume = 50 | issue = 76 | pages = 11154–11157 | date = October 2014 | pmid = 25110984 | doi = 10.1039/C4CC03578J }}</ref>

==Side effects and adverse reactions==

The side effects of {{sm|l}}-DOPA may include:

* [[Hypertension]], especially if the dosage is too high

* [[Heart arrhythmia|Arrhythmia]]s, although these are uncommon

* [[Nausea]], which is often reduced by taking the drug with food, although [[protein]] reduces drug absorption. {{sm|l}}-DOPA is an amino acid, so protein competitively inhibits {{sm|l}}-DOPA absorption.

* Gastrointestinal bleeding

* Disturbed [[respiration (physiology)|respiration]], which is not always harmful, and can actually benefit patients with upper airway obstruction

* [[alopecia|Hair loss]]

* [[Disorientation]] and [[mental confusion|confusion]]

* Extreme [[emotion]]al states, particularly [[anxiety]], but also excessive [[libido]]

* Vivid [[dream]]s or [[insomnia]]

* [[Auditory hallucination|Auditory]] or [[Hallucination#Visual|visual hallucinations]]

* Effects on learning; some evidence indicates it improves [[working memory]], while impairing other complex functions

* [[Somnolence]] and [[narcolepsy]]

* A condition similar to [[stimulant psychosis]]

Although many adverse effects are associated with {{sm|l}}-DOPA, in particular psychiatric ones, it has fewer than other [[Management of Parkinson's disease#Medication|antiparkinsonian agent]]s, such as [[anticholinergic]]s and [[dopamine receptor agonist]]s.

More serious are the effects of chronic {{sm|l}}-DOPA administration in the treatment of Parkinson's disease, which include:

* End-of-dose deterioration of function

* "On/off" oscillations

* Freezing during movement

* Dose failure ([[drug resistance]])

* [[Dyskinesia]] at peak dose ([[levodopa-induced dyskinesia]])

* Possible dopamine dysregulation: The long-term use of {{sm|l}}-DOPA in Parkinson's disease has been linked to the so-called [[dopamine dysregulation syndrome]].<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>

Clinicians try to avoid these side effects and adverse reactions by limiting {{sm|l}}-DOPA doses as much as possible until absolutely necessary.

The long term use of L-Dopa increases oxidative stress through [[monoamine oxidase]] led enzymatic degradation of synthesized dopamine causing neuronal damage and cytotoxicity. The oxidative stress is caused by the formation of [[reactive oxygen species]] (H₂O₂) during the monoamine oxidase led metabolism of dopamine. It is further perpetuated by the richness of Fe²⁺ ions in striatum via the Fenton reaction and intracellular [[autooxidation]]. The increased oxidation can potentially cause mutations in DNA due to the formation of [[8-Oxoguanine|8-oxoguanine]], which is capable of pairing with adenosine during [[mitosis]].<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>

==History==

In work that earned him a [[Nobel Prize in Physiology or Medicine|Nobel Prize]] in 2000, [[Swedish people|Swedish]] scientist [[Arvid Carlsson]] first showed in the 1950s that administering {{sm|l}}-DOPA to animals with drug-induced ([[reserpine]]) Parkinsonian [[symptom]]s caused a reduction in the intensity of the animals' symptoms. In 1960/61 [[Oleh Hornykiewicz]], after discovering greatly reduced levels of dopamine in autopsied brains of patients with Parkinson's disease,<ref name="pmid13726012">{{cite journal | vauthors = Ehringer H, Hornykiewicz O | title = [Distribution of noradrenaline and dopamine (3-hydroxytyramine) in the human brain and their behavior in diseases of the extrapyramidal system] | 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 {{sm|l}}-DOPA in patients.<ref name="pmid13869404">{{cite journal | vauthors = Birkmayer W, Hornykiewicz O | title = [The L-3,4-dioxyphenylalanine (DOPA)-effect in Parkinson-akinesia] | 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 [[George Cotzias]] 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 [[Lasker Prize]].<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= 2016-01-05}}, accessed April 1, 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 [[neurology|neurologist]] [[Oliver Sacks]] describes this treatment in human patients with [[encephalitis lethargica]] in his 1973 book ''[[Awakenings (book)|Awakenings]]'', upon which [[Awakenings|the 1990 movie of the same name]] is based. The first study reporting improvements in patients with Parkinson's disease resulting from treatment with L-dopa 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>

The 2001 [[Nobel Prize in Chemistry]] was also related to {{sm|l}}-DOPA: the Nobel Committee awarded one-quarter of the prize to [[William S. Knowles]] for his work on chirally catalysed [[hydrogenation]] reactions, the most noted example of which was used for the synthesis of {{sm|l}}-DOPA.<ref>{{cite journal | doi = 10.1021/ar00087a006 | title = Asymmetric hydrogenation | year = 1983 | vauthors = Knowles WS | journal = Accounts of Chemical Research | volume = 16 | issue = 3 | pages = 106–112}}</ref><ref>{{cite web | url = http://www.chem.wisc.edu/areas/reich/syntheses/dopa-monsanto-knowles.htm | title = Synthetic scheme for total synthesis of DOPA, L- (Monsanto) | publisher = UW Madison, Department of Chemistry | access-date = Sep 30, 2013}}</ref><ref>{{cite journal| vauthors = Knowles WS |title=Application of organometallic catalysis to the commercial production of L-DOPA|journal=Journal of Chemical Education|date=March 1986|volume=63|issue=3|pages=222|doi=10.1021/ed063p222|bibcode=1986JChEd..63..222K}}</ref>

:[[File:L-dopaSyn.svg|thumb|center|550px|Synthesis of {{sm|l}}-DOPA via hydrogenation with C₂-symmetric diphosphine.]]

==Research==

=== Age-related macular degeneration ===

In 2015, a retrospective analysis comparing the incidence of [[age-related macular degeneration]] (AMD) between patients taking versus not taking {{sm|l}}-DOPA found that the drug delayed onset of AMD by around 8 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}}

=== Role in plants and in the environment ===

In plants, L-DOPA functions as an [[allelochemical]] which inhibits the growth of certain species, and is produced and secreted by a few legume species such as the broad bean [[Vicia faba]] and the velvet bean [[Mucuna pruriens]].<ref>{{cite journal | vauthors = Fujii Y, Shibuya T, Yasuda T| title = L-3,4-Dihydroxyphenylalanine as an Allelochemical Candidate from Mucuna pruriens (L.) DC. var. utilis | journal = Agricultural and Biological Chemistry | volume = 55 | issue = 2 | pages = 617–618 | date = 1991 | doi = 10.1080/00021369.1991.10870627 }}</ref> Its effect is strongly dependent on the pH and the reactivity of iron in the soil.<ref>{{cite journal | vauthors = Hsieh EJ, Liao SW, Chang CY, Tseng CH, Wang SL, Grillet L| title = L-DOPA induces iron accumulation in roots of Ipomoea aquatica and Arabidopsis thaliana in a pH-dependent manner | journal = Botanical Studies | volume = 64 | issue = 24 | pages = 617–618 | date = 2023 | pmid = 37620733 | pmc = 10449704 | doi = 10.1186/s40529-023-00396-7 | doi-access = free | bibcode = 2023BotSt..64...24H }}</ref>

== See also ==

* [[D-DOPA|{{sm|d}}-DOPA]] (Dextrodopa)

* [[L-DOPS|{{sm|l}}-DOPS]] (Droxidopa)

* [[Methyldopa]] (Aldomet, Apo-Methyldopa, Dopamet, Novomedopa, etc.)

* [[Dopamine]] (Intropan, Inovan, Revivan, Rivimine, Dopastat, Dynatra, etc.)

* [[Ciladopa]]

<!-- already mentioned* [[Norepinephrine]] (Noradrenaline; Levophed, etc.)

* [[Epinephrine]] (Adrenaline; Adrenalin, EpiPen, Twinject, etc.) -->

* [[Neuroleptic malignant syndrome]]

* [[Melanin]] (a metabolite)

== 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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