l-DOPA Pronunciation , Trade names Larodopa, Dopar, Inbrija, others AHFS/ Drugs.com Professional Drug Facts MedlinePlus a619018 License data
Pregnancy category Routes of administration By mouth, intravenous ATC code Legal status
AU: S4 (Prescription only)
UK: POM (Prescription only)
US: ℞-only (some forms are OTC) Rx-only EU: Bioavailability 30% Metabolism Aromatic- l-amino-acid decarboxylase Elimination half-life 0.75–1.5 hours Excretion renal 70–80%
S)-2-Amino-3-(3,4-dihydroxyphenyl)propanoic acid CAS Number PubChem CID IUPHAR/BPS DrugBank ChemSpider UNII KEGG ChEBI ChEMBL CompTox Dashboard ( EPA) ECHA InfoCard 100.000.405 Formula C 9 H 11 N O 4 Molar mass g·mol 197.190 −1 3D model ( JSmol)
(verify) , also known as l-DOPA levodopa and , is an amino acid that is made and used as part of the normal l-3,4-dihydroxyphenylalanine biology of some plants and animals, including humans. Humans, as well as a portion of the other animals that utilize l-DOPA, make it via biosynthesis from the amino acid . l-tyrosine l-DOPA is the precursor to the neurotransmitters dopamine, norepinephrine (noradrenaline), and epinephrine (adrenaline), which are collectively known as catecholamines. Furthermore, l-DOPA itself mediates neurotrophic factor release by the brain and CNS.   l-DOPA can be manufactured and in its pure form is sold as a psychoactive drug with the INN levodopa; trade names include Sinemet, Pharmacopa, Atamet, and Stalevo. As a drug, it is used in the clinical treatment of Parkinson's disease and dopamine-responsive dystonia.
l-DOPA has a counterpart with opposite chirality, . As is true for many molecules, the human body produces only one of these d-DOPA isomers (the l-DOPA form). The enantiomeric purity of l-DOPA may be analyzed by determination of the optical rotation or by chiral thin-layer chromatography.
l-DOPA crosses the protective blood-brain barrier, whereas dopamine itself cannot. Thus,  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. Bradykinesia and rigidity are the most responsive symptoms while tremors are less responsive to levodopa therapy. Speech, swallowing disorders, postural instability and freezing gait are the least responsive symptoms.
l-DOPA has entered the central nervous system, it is converted into dopamine by the enzyme aromatic , also known as l-amino acid decarboxylase DOPA decarboxylase. Pyridoxal phosphate ( vitamin B) is a required 6 cofactor in this reaction, and may occasionally be administered along with l-DOPA, usually in the 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
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 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 side effects seen with sole L-DOPA administration. To bypass these effects, it is standard clinical practice to coadminister (with l-DOPA) a peripheral DOPA decarboxylase inhibitor (DDCI) such as carbidopa (medicines containing carbidopa, either alone or in combination with l-DOPA, are branded as Lodosyn (  Aton Pharma)  Sinemet ( Merck Sharp & Dohme Limited), Pharmacopa ( Jazz Pharmaceuticals), Atamet ( UCB), Syndopa and Stalevo ( Orion Corporation) or with a benserazide (combination medicines are branded Madopar or Prolopa), to prevent the peripheral synthesis of dopamine from l-DOPA).
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. It was approved by the United States  Food and Drug Administration on December 21, 2018, and is marketed by Acorda Therapeutics.
pyridoxine without a DDCI accelerates the peripheral decarboxylation of l-DOPA to such an extent that it negates the effects of l-DOPA administration, a phenomenon that historically caused great confusion.
l-DOPA, co-administered with a peripheral DDCI, is efficacious for the short-term treatment of restless leg syndrome.
The two types of response seen with administration of
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 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.
l-DOPA is produced from the amino acid l- tyrosine by the enzyme tyrosine hydroxylase. l-DOPA can act as an l-tyrosine mimetic and be incorporated into proteins by mammalian cells in place of L-tyrosine, generating protease-resistant and aggregate-prone proteins in vitro and may contribute to neurotoxicity with chronic l-DOPA administration.
It is also the precursor for the  monoamine or catecholamine neurotransmitters dopamine, norepinephrine (noradrenaline), and epinephrine (adrenaline). Dopamine is formed by the decarboxylation of l-DOPA by aromatic (AADC).
l-amino acid decarboxylase l-DOPA can be directly metabolized by catechol- to O-methyl transferase 3-, and then further to vanillactic acid. This metabolic pathway is nonexistent in the healthy body, but becomes important after peripheral O-methyldopa l-DOPA administration in patients with Parkinson's disease or in the rare cases of patients with AADC enzyme deficiency.
 l-Phenylalanine, l-tyrosine, and l-DOPA are all precursors to the biological pigment melanin. The enzyme tyrosinase catalyzes the oxidation of l-DOPA to the reactive intermediate dopaquinone, which reacts further, eventually leading to melanin oligomers. In addition, tyrosinase can convert tyrosine directly to l-DOPA in the presence of a reducing agent such as ascorbic acid.
Side effects and adverse reactions
The side effects of
l-DOPA may include:
Hypertension, especially if the dosage is too high
Arrhythmias, although these are uncommon
Nausea, which is often reduced by taking the drug with food, although protein reduces drug absorption. l-DOPA is an amino acid, so protein competitively inhibits l-DOPA absorption. Gastrointestinal bleeding
respiration, which is not always harmful, and can actually benefit patients with upper airway obstruction
Disorientation and confusion Extreme
emotional states, particularly anxiety, but also excessive libido Vivid
dreams or insomnia
Auditory or 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
l-DOPA, in particular psychiatric ones, it has fewer than other antiparkinsonian agents, such as anticholinergics and dopamine receptor agonists.
More serious are the effects of chronic
l-DOPA administration in the treatment of Parkinson's disease, which include:
Clinicians try to avoid these side effects and adverse reactions by limiting
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 (H 2O 2) during the monoamine oxidase led metabolism of dopamine. It is further perpetuated by the richness of Fe 2+ 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, which is capable of pairing with adenosine during mitosis.
In work that earned him a
Nobel Prize in 2000, Swedish scientist Arvid Carlsson first showed in the 1950s that administering l-DOPA to animals with drug-induced ( reserpine) Parkinsonian symptoms 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, published together with the neurologist Walther Birkmayer dramatic therapeutic antiparkinson effects of intravenously administered  l-DOPA in patients. This treatment was later extended to manganese poisoning and later Parkinsonism by  George Cotzias and his coworkers, who used greatly increased oral doses, for which they won the 1969  Lasker Prize.  . The  neurologist Oliver Sacks describes this treatment in human patients with encephalitis lethargica in his 1973 book , 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.
Nobel Prize in Chemistry was also related to 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 l-DOPA.  
l-DOPA via hydrogenation with C 2-symmetric diphosphine.
Herbal extracts containing l-DOPA are available; high-yielding sources include (velvet bean), Mucuna pruriens and  (broad bean), while other sources include the genera Vicia faba , Phanera , Piliostigma , Cassia , and Canavalia . Dalbergia
l-DOPA is a key compound in the formation of marine adhesive proteins, such as those found in mussels.  It is believed to be responsible for the water-resistance and rapid curing abilities of these proteins.  l-DOPA may also be used to prevent surfaces from fouling by bonding antifouling polymers to a susceptible substrate. The versatile chemistry of L-DOPA can be exploited in nanotechnology.  For example, DOPA-containing self-assembling peptides were found to form functional nanostructures, adhesives and gels.    
In 2015, a retrospective analysis comparing the incidence of
age-related macular degeneration (AMD) between patients taking versus not taking 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.
Methyldopa (Aldomet, Apo-Methyldopa, Dopamet, Novomedopa, etc.)
Dopamine (Intropan, Inovan, Revivan, Rivimine, Dopastat, Dynatra, etc.)
Neuroleptic malignant syndrome Melanin (a metabolite)
S. T. Howard, M. B. Hursthouse, C. W. Lehmann, E. A. Poyner (1995). "Experimental and theoretical determination of electronic properties in Ldopa". . Acta Crystallogr. B 51: 328–337. doi: 10.1107/S0108768194011407.
((: CS1 maint: uses authors parameter (
cite journal)) link)
^ a b
"Levodopa Use During Pregnancy". Drugs.com. 12 July 2019 . Retrieved . 27 September 2020
Lopez VM, Decatur CL, Stamer WD, Lynch RM, McKay BS (September 2008). "L-DOPA is an endogenous ligand for OA1". PLOS Biology. 6 (9): e236. doi: 10.1371/journal.pbio.0060236. PMC . 2553842 PMID 18828673.
Hiroshima Y, Miyamoto H, Nakamura F, Masukawa D, Yamamoto T, Muraoka H, Kamiya M, Yamashita N, Suzuki T, Matsuzaki S, Endo I, Goshima Y (January 2014). "The protein Ocular albinism 1 is the orphan GPCR GPR143 and mediates depressor and bradycardic responses to DOPA in the nucleus tractus solitarii". British Journal of Pharmacology. 171 (2): 403–14. doi: 10.1111/bph.12459. PMC . 3904260 PMID 24117106.
Martens, J, Günther, K, Schickedanz M (1986). "Resolution of Optical Isomers by Thin-Layer Chromatography: Enantiomeric Purity of Methyldopa". Arch. Pharm. 319 (6): 572–574. doi: 10.1002/ardp.19863190618. S2CID 97903386.
Hardebo, Jan Erik; Owman, Christer (1980). "Barrier mechanisms for neurotransmitter monoamines and their precursors at the blood-brain interface". Annals of Neurology. 8 (1): 1–11. doi: 10.1002/ana.410080102. ISSN 1531-8249. PMID 6105837. S2CID 22874032.
Ovallath, Sujith; Sulthana, Bahiya (2017). "Levodopa: History and Therapeutic Applications". Annals of Indian Academy of Neurology. 20 (3): 185–189. doi: 10.4103/aian.AIAN_241_17 (inactive 31 July 2022). ISSN 0972-2327. PMC . 5586109 PMID 28904446.
((: CS1 maint: DOI inactive as of July 2022 (
cite journal)) link)
"Medicare D". Medicare. 2014 . Retrieved . 12 November 2015
"Lodosyn", Drugs, nd , retrieved 12 November 2012
"Inbrija Prescribing Information" (PDF) . Retrieved . February 14, 2019
"Acorda Therapeutics Announces FDA Approval of INBRIJA™ (levodopa inhalation powder)". ir.acorda.com . Retrieved . 2019-02-14
Scholz H, Trenkwalder C, Kohnen R, Riemann D, Kriston L, Hornyak M (February 2011). Cochrane Movement Disorders Group (ed.). "Levodopa for restless legs syndrome". The Cochrane Database of Systematic Reviews (2): CD005504. doi: 10.1002/14651858.CD005504.pub2. PMC . 8889887 PMID 21328278.
Broadley KJ (March 2010). "The vascular effects of trace amines and amphetamines". Pharmacology & Therapeutics. 125 (3): 363–375. doi: 10.1016/j.pharmthera.2009.11.005. PMID 19948186.
Lindemann L, Hoener MC (May 2005). "A renaissance in trace amines inspired by a novel GPCR family". Trends in Pharmacological Sciences. 26 (5): 274–281. doi: 10.1016/j.tips.2005.03.007. PMID 15860375.
Wang X, Li J, Dong G, Yue J (February 2014). "The endogenous substrates of brain CYP2D". European Journal of Pharmacology. 724: 211–218. doi: 10.1016/j.ejphar.2013.12.025. PMID 24374199.
Rodgers, KJ (March 2014). "Non-protein amino acids and neurodegeneration: the enemy within". Experimental Neurology. 253: 192–6. doi: 10.1016/j.expneurol.2013.12.010. PMID 24374297. S2CID 2288729.
Hyland K, Clayton PT (December 1992). "Aromatic L-amino acid decarboxylase deficiency: diagnostic methodology" (PDF). Clinical Chemistry. 38 (12): 2405–10. doi: . 10.1093/clinchem/38.12.2405 PMID 1281049. Archived from the original (PDF) on 2011-06-07 . Retrieved . 2008-10-16
Ito S, Kato T, Shinpo K, Fujita K (September 1984). "Oxidation of tyrosine residues in proteins by tyrosinase. Formation of protein-bonded 3,4-dihydroxyphenylalanine and 5-S-cysteinyl-3,4-dihydroxyphenylalanine". The Biochemical Journal. 222 (2): 407–11. doi: 10.1042/bj2220407. PMC . 1144193 PMID 6433900.
Merims D, Giladi N (2008). "Dopamine dysregulation syndrome, addiction and behavioral changes in Parkinson's disease". Parkinsonism & Related Disorders. 14 (4): 273–80. doi: 10.1016/j.parkreldis.2007.09.007. PMID 17988927.
Dorszewska J, Prendecki M, Lianeri M, Kozubski W (February 2014). "Molecular Effects of L-dopa Therapy in Parkinson's Disease". Current Genomics. 15 (1): 11–7. doi: 10.2174/1389202914666131210213042. PMC . 3958954 PMID 24653659.
Ehringer H, Hornykiewicz O (December 1960). "[Distribution of noradrenaline and dopamine (3-hydroxytyramine) in the human brain and their behavior in diseases of the extrapyramidal system]". Klinische Wochenschrift. 38 (24): 1236–9. doi: 10.1007/BF01485901. PMID 13726012. S2CID 32896604.
Birkmayer W, Hornykiewicz O (November 1961). "[The L-3,4-dioxyphenylalanine (DOPA)-effect in Parkinson-akinesia]". Wiener Klinische Wochenschrift. 73: 787–8. PMID 13869404.
Cotzias GC, Papavasiliou PS, Gellene R (July 1969). "L-dopa in parkinson's syndrome". The New England Journal of Medicine. 281 (5): 272. doi: 10.1056/NEJM196907312810518. PMID 5791298.
Lasker Award 1969 Description Archived 2016-01-05 at the Wayback Machine, accessed April 1, 2013
^ Tanya Simuni and Howard Hurtig. "Levadopa: A Pharmacologic Miracle Four Decades Later", in
Parkinson's Disease: Diagnosis and Clinical Management (Google eBook). Eds. Stewart A Factor and William J Weiner. Demos Medical Publishing, 2008
New England Journal of Medicine  278 (11) : 630 (Cotzias, G) "L-Dopa for Parkinsonism"
Knowles WS (1983). "Asymmetric hydrogenation". Accounts of Chemical Research. 16 (3): 106–112. doi: 10.1021/ar00087a006.
"Synthetic scheme for total synthesis of DOPA, L- (Monsanto)". UW Madison, Department of Chemistry . Retrieved . Sep 30, 2013
Knowles WS (March 1986). "Application of organometallic catalysis to the commercial production of L-DOPA". Journal of Chemical Education. 63 (3): 222. Bibcode: 1986JChEd..63..222K. doi: 10.1021/ed063p222.
Pankaj Oudhia. "Kapikachu or Cowhage" . Retrieved . Nov 3, 2013
Ingle PK (May–June 2003). "L-DOPA bearing plants". Natural Product Radiance. 2 (3): 126–133.
Waite JH, Andersen NH, Jewhurst S, Sun C (2005). "Mussel Adhesion: Finding the Tricks Worth Mimicking". J Adhesion. 81 (3–4): 1–21. doi: 10.1080/00218460590944602. S2CID 136967853.
"Study Reveals Details Of Mussels' Tenacious Bonds". Science Daily. Aug 16, 2006 . Retrieved . Sep 30, 2013
Mussel Adhesive Protein Mimetics Archived 2006-05-29 at the Wayback Machine
Giuri, Demetra; Ravarino, Paolo; Tomasini, Claudia (2021). "l -Dopa in small peptides: an amazing functionality to form supramolecular materials". Organic & Biomolecular Chemistry. 19 (21): 4622–4636. doi: 10.1039/D1OB00378J. ISSN 1477-0520. PMID 33978030. S2CID 234474122.
Fichman, Galit; Adler-Abramovich, Lihi; Manohar, Suresh; Mironi-Harpaz, Iris; Guterman, Tom; Seliktar, Dror; Messersmith, Phillip B.; Gazit, Ehud (2014-07-22). "Seamless Metallic Coating and Surface Adhesion of Self-Assembled Bioinspired Nanostructures Based on Di-(3,4-dihydroxy- l -phenylalanine) Peptide Motif". ACS Nano. 8 (7): 7220–7228. doi: 10.1021/nn502240r. ISSN 1936-0851. PMC . 4108209 PMID 24936704.
Fichman, Galit; Guterman, Tom; Adler-Abramovich, Lihi; Gazit, Ehud (September 2014). "The Use of the Calcitonin Minimal Recognition Module for the Design of DOPA-Containing Fibrillar Assemblies". Nanomaterials. 4 (3): 726–740. doi: . 10.3390/nano4030726 ISSN 2079-4991. PMC . 5304689 PMID 28344244.
Fichman, Galit; Andrews, Caroline; Patel, Nimit L.; Schneider, Joel P. (October 2021). "Antibacterial Gel Coatings Inspired by the Cryptic Function of a Mussel Byssal Peptide". Advanced Materials. 33 (40): 2103677. doi: 10.1002/adma.202103677. ISSN 0935-9648. PMC 8492546. PMID 34423482.
Maity, Sibaprasad; Nir, Sivan; Zada, Tal; Reches, Meital (2014-08-26). "Self-assembly of a tripeptide into a functional coating that resists fouling". Chemical Communications. 50 (76): 11154–11157. doi: 10.1039/C4CC03578J. ISSN 1364-548X. PMID 25110984.
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 (March 2016). "Mining Retrospective Data for Virtual Prospective Drug Repurposing: L-DOPA and Age-related Macular Degeneration". The American Journal of Medicine. 129 (3): 292–8. doi: 10.1016/j.amjmed.2015.10.015. PMC . 4841631 PMID 26524704.
"Levodopa". Drug Information Portal. U.S. National Library of Medicine.