Array ( [0] => {{short description|Chemical compound}} [1] => {{cs1 config|name-list-style=vanc|display-authors=6}} [2] => {{DISPLAYTITLE:L-DOPA}} [3] => {{Infobox drug [4] => | Watchedfields = changed [5] => | verifiedrevid = 461087196 [6] => | IUPAC_name = (''S'')-2-Amino-3-(3,4-dihydroxyphenyl)propanoic acid [7] => | image = 3,4-Dihydroxy-L-phenylalanin (Levodopa).svg [8] => | caption = [[Skeletal formula]] of L-DOPA [9] => | image2 = L-DOPA-from-xtal-view-2-3D-bs-17.png [10] => | width2 = 180px [11] => | caption2 = [[Ball-and-stick model]] of the [[zwitterion]]ic form of L-DOPA found in the [[crystal structure]]{{ 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 }} [12] => | drug_name = {{sm|l}}-DOPA [13] => [14] => [15] => | pronounce = {{IPAc-en|ˌ|ɛ|l|ˈ|d|oʊ|p|ə}}, {{IPAc-en|ˌ|l|ɛ|v|oʊ|ˈ|d|oʊ|p|ə}} [16] => | tradename = Larodopa, Dopar, Inbrija, others [17] => | Drugs.com = {{drugs.com|ppa|levodopa-oral-inhalation}} [18] => | MedlinePlus = a619018 [19] => | licence_EU = yes [20] => | DailyMedID = Levodopa [21] => | licence_US = [22] => | pregnancy_AU = B3 [23] => | pregnancy_AU_comment = {{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}} [24] => | pregnancy_US = N [25] => | pregnancy_US_comment = [26] => | routes_of_administration = [[Oral administration|By mouth]], [[intravenous]] [27] => | ATC_prefix = N04 [28] => | ATC_suffix = BA01 [29] => [30] => [31] => | legal_AU = S4 [32] => | legal_AU_comment = [33] => | legal_BR = [34] => | legal_BR_comment = [35] => | legal_CA = [36] => | legal_CA_comment = [37] => | legal_DE = [38] => | legal_DE_comment = [39] => | legal_NZ = [40] => | legal_NZ_comment = [41] => | legal_UK = POM [42] => | legal_UK_comment = [43] => | legal_US = Rx-only [44] => | legal_US_comment = (some forms are OTC) [45] => | legal_EU = Rx-only [46] => | legal_EU_comment = [47] => | legal_UN = [48] => | legal_UN_comment = [49] => | legal_status = [50] => [51] => [52] => | bioavailability = 30% [53] => | metabolism = [[Aromatic-L-amino-acid decarboxylase|Aromatic-{{sm|l}}-amino-acid decarboxylase]] [54] => | elimination_half-life = 0.75–1.5 hours [55] => | excretion = [[renal]] 70–80% [56] => [57] => [58] => | CAS_number_Ref = {{cascite|correct|??}} [59] => | CAS_number = 59-92-7 [60] => | PubChem = 6047 [61] => | IUPHAR_ligand = 3639 [62] => | DrugBank_Ref = {{drugbankcite|correct|drugbank}} [63] => | DrugBank = DB01235 [64] => | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} [65] => | ChemSpiderID = 5824 [66] => | UNII_Ref = {{fdacite|correct|FDA}} [67] => | UNII = 46627O600J [68] => | KEGG_Ref = {{keggcite|correct|kegg}} [69] => | KEGG = D00059 [70] => | ChEBI_Ref = {{ebicite|correct|EBI}} [71] => | ChEBI = 15765 [72] => | ChEMBL_Ref = {{ebicite|correct|EBI}} [73] => | ChEMBL = 1009 [74] => [75] => [76] => | C=9 | H=11 | N=1 | O=4 [77] => | smiles = O=C(O)[C@@H](N)Cc1cc(O)c(O)cc1 [78] => | StdInChI_Ref = {{stdinchicite|correct|chemspider}} [79] => | 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 [80] => | StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} [81] => | StdInChIKey = WTDRDQBEARUVNC-LURJTMIESA-N [82] => }} [83] => '''{{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 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.{{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 }}{{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 }} 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.{{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 }} {{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]]. [84] => [85] => {{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]].{{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 }} [86] => [87] => ==Medical use== [88] => {{sm|l}}-DOPA crosses the protective [[blood–brain barrier]], whereas [[dopamine]] itself cannot.{{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 }} 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.{{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 }} [89] => [90] => 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. [91] => [92] => 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 L-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]]{{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}} ([[Valeant Pharmaceuticals|Aton Pharma]]){{citation |url=https://www.drugs.com/pro/lodosyn.html |title=Lodosyn |work=Drugs |date=nd |access-date=12 November 2012 }} [[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.{{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 }} [93] => [94] => 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]].{{Cite web|url=https://www.inbrija.com/prescribing-information.pdf|title=Inbrija Prescribing Information |access-date=February 14, 2019}} It was approved by the United States [[Food and Drug Administration]] on December 21, 2018, and is marketed by [[Acorda Therapeutics]].{{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}} [95] => [96] => 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. [97] => [98] => In addition, {{sm|l}}-DOPA, co-administered with a peripheral DDCI, is efficacious for the short-term treatment of [[restless leg syndrome]].{{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 }} [99] => [100] => The two types of response seen with administration of {{sm|l}}-DOPA are: [101] => * The short-duration response is related to the half-life of the drug. [102] => * 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. [103] => [104] => ==Biological role== [105] => {{phenylalanine biosynthesis|align=right}} [106] => {{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.{{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 }} [107] => 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). [108] => [109] => {{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.{{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 }} [110] => [111] => {{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]].{{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 }} [112] => [113] => ==Marine adhesion== [114] => {{sm|l}}-DOPA is a key [[chemical compound|compound]] in the formation of [[marine adhesive protein]]s, such as those found in [[mussel]]s.{{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 }}{{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}} 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]].{{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 }} The versatile chemistry of L-DOPA can be exploited in nanotechnology.{{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 }} For example, DOPA-containing self-assembling peptides were found to form functional nanostructures, adhesives and gels.{{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 }}{{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 }}{{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 }}{{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 }} [115] => [116] => ==Side effects and adverse reactions== [117] => The side effects of {{sm|l}}-DOPA may include: [118] => * [[Hypertension]], especially if the dosage is too high [119] => * [[Heart arrhythmia|Arrhythmia]]s, although these are uncommon [120] => * [[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. [121] => * Gastrointestinal bleeding [122] => * Disturbed [[respiration (physiology)|respiration]], which is not always harmful, and can actually benefit patients with upper airway obstruction [123] => * [[alopecia|Hair loss]] [124] => * [[Disorientation]] and [[mental confusion|confusion]] [125] => * Extreme [[emotion]]al states, particularly [[anxiety]], but also excessive [[libido]] [126] => * Vivid [[dream]]s or [[insomnia]] [127] => * [[Auditory hallucination|Auditory]] or [[Hallucination#Visual|visual hallucinations]] [128] => * Effects on learning; some evidence indicates it improves [[working memory]], while impairing other complex functions [129] => * [[Somnolence]] and [[narcolepsy]] [130] => * A condition similar to [[stimulant psychosis]] [131] => [132] => 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. [133] => [134] => More serious are the effects of chronic {{sm|l}}-DOPA administration in the treatment of Parkinson's disease, which include: [135] => * End-of-dose deterioration of function [136] => * "On/off" oscillations [137] => * Freezing during movement [138] => * Dose failure ([[drug resistance]]) [139] => * [[Dyskinesia]] at peak dose ([[levodopa-induced dyskinesia]]) [140] => * 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]].{{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 }} [141] => [142] => Clinicians try to avoid these side effects and adverse reactions by limiting {{sm|l}}-DOPA doses as much as possible until absolutely necessary. [143] => [144] => 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]].{{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 }} [145] => [146] => ==History== [147] => 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,{{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 }} published together with the neurologist [[Walther Birkmayer]] dramatic therapeutic antiparkinson effects of intravenously administered {{sm|l}}-DOPA in patients.{{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 }} This treatment was later extended to manganese poisoning and later Parkinsonism by [[George Cotzias]] and his coworkers,{{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 }} who used greatly increased oral doses, for which they won the 1969 [[Lasker Prize]].{{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{{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 }} 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.{{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 }} [148] => [149] => 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.{{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}}{{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}}{{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}} [150] => [151] => :[[File:L-dopaSyn.svg|thumb|center|550px|Synthesis of {{sm|l}}-DOPA via hydrogenation with C2-symmetric diphosphine.]] [152] => [153] => ==Research== [154] => === Age-related macular degeneration === [155] => 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.{{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 }}{{primary source inline|date=December 2016}} [156] => [157] => === Role in plants and in the environment === [158] => 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]].{{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 }} Its effect is strongly dependent on the pH and the reactivity of iron in the soil.{{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 }} [159] => [160] => == See also == [161] => * [[D-DOPA|{{sm|d}}-DOPA]] (Dextrodopa) [162] => * [[L-DOPS|{{sm|l}}-DOPS]] (Droxidopa) [163] => * [[Methyldopa]] (Aldomet, Apo-Methyldopa, Dopamet, Novomedopa, etc.) [164] => * [[Dopamine]] (Intropan, Inovan, Revivan, Rivimine, Dopastat, Dynatra, etc.) [165] => * [[Ciladopa]] [166] => [168] => * [[Neuroleptic malignant syndrome]] [169] => * [[Melanin]] (a metabolite) [170] => [171] => == References == [172] => {{Reflist}} [173] => [174] => == External links == [175] => * {{cite web | url = https://druginfo.nlm.nih.gov/drugportal/name/levodopa | publisher = U.S. National Library of Medicine | work = Drug Information Portal | title = Levodopa }} [176] => [177] => {{Stimulants}} [178] => {{Antiparkinson}} [179] => {{Supplements}} [180] => {{Amino acids}} [181] => {{Amino acid metabolism enzymes}} [182] => {{Neurotransmitter metabolism intermediates}} [183] => {{Dopaminergics}} [184] => {{Portal bar | Medicine}} [185] => [186] => {{DEFAULTSORT:DOPA, L-}} [187] => [[Category:Alpha-Amino acids]] [188] => [[Category:Aromatic amino acids]] [189] => [[Category:Antiparkinsonian agents]] [190] => [[Category:Carbonic anhydrase activators]] [191] => [[Category:Catecholamines]] [192] => [[Category:Dopamine agonists]] [193] => [[Category:Neurotransmitter precursors]] [194] => [[Category:Monoamine precursors]] [] => )
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L-DOPA

L-DOPA, also known as levodopa, is a medication used to treat the symptoms of Parkinson's disease. It is a naturally occurring chemical in the brain that is converted into dopamine, a neurotransmitter responsible for controlling movement.

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It is a naturally occurring chemical in the brain that is converted into dopamine, a neurotransmitter responsible for controlling movement. The Wikipedia page on L-DOPA provides a comprehensive overview of the drug, including its history, chemistry, pharmacology, and therapeutic uses. The page explains how L-DOPA was first discovered in the early 20th century and later found to be effective in relieving the symptoms of Parkinson's disease, such as tremors, stiffness, and difficulty with movement. The page also explores the chemistry of L-DOPA, detailing its structure and mechanism of action. It explains that L-DOPA is a precursor to dopamine and is converted into this neurotransmitter in the brain. By increasing dopamine levels, L-DOPA helps to restore the balance of neurotransmitters disrupted in Parkinson's disease. Moreover, the page discusses the pharmacology of L-DOPA, including its absorption, metabolism, and elimination from the body. It explains how the drug needs to be converted into its active form in the brain and highlights some factors that can affect its efficacy. Additionally, the Wikipedia page covers the therapeutic uses of L-DOPA beyond Parkinson's disease. It explores its potential applications in other movement disorders, such as restless legs syndrome, and discusses ongoing research investigating its role in conditions like attention deficit hyperactivity disorder (ADHD) and depression. The page also addresses some of the limitations and challenges associated with L-DOPA therapy. It explains that while it is highly effective in managing the symptoms of Parkinson's disease, long-term use can lead to complications, such as dyskinesias (involuntary movements) and motor fluctuations. It also touches on the issue of dopamine loss in the brain over time, which can reduce the drug's effectiveness. Overall, the Wikipedia page on L-DOPA provides a comprehensive and detailed examination of this medication, covering its history, chemistry, pharmacology, therapeutic uses, limitations, and ongoing research areas.

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