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L-DOPA (L-3,4-dihydroxyphenylalanine; Levodopa; Sinemet, Parcopa, Atamet, Stalevo, Madopar, Prolopa, etc) is a naturally-occurring dietary supplement and psychoactive drug found in certain kinds of food and herbs (e.g. Mucuna pruriens, or velvet bean), and is synthesized from the essential amino acids L-phenylalanine (PHE) and L-tyrosine (TYR) in the mammalian body and brain. L-DOPA is the precursor to the neurotransmitters dopamine, norepinephrine (noradrenaline), and epinephrine (adrenaline) collectively known as catecholamines. Aside from its natural and essential biological role, L-DOPA is also used in the clinical treatment of Parkinson's disease (PD) and dopamine-responsive dystonia (DRD).

Therapeutic use

L-DOPA is used to increase dopamine concentrations in the treatment of PD and DRD since it is capable of crossing the protective blood-brain barrier (BBB), whereas dopamine itself cannot. Once L-DOPA has entered the central nervous system (CNS), it is converted into dopamine by the enzyme aromatic L-amino acid decarboxylase (AADC), also known as DOPA decarboxylase (DDC). Pyridoxal phosphate (PLP; Vitamin B6) is a required cofactor in this reaction, and may occasionally be administered along with L-DOPA, usually in the form of pyridoxine.

Besides the CNS, L-DOPA is also converted into dopamine from within the peripheral nervous system (PNS). This property is the cause of many of the adverse side effect seen with sole L-DOPA administration. In order to bypass these effects, it is standard clinical practice to co-administer a peripheral DOPA decarboxylase inhibitor (DDCI) such as carbidopa (Lodosyn, Sinemet, Parcopa, Atamet, Stalevo) or benserazide (Madopar, Prolopa) with L-DOPA in augmentation, for the purpose of preventing the peripheral synthesis of dopamine from L-DOPA. Co-administration of pyridoxine without a DDCI accelerates the peripheral decarboxylation of L-DOPA to such an extent that it cancels out the effects of L-DOPA administration, a phenomenon that historically caused great confusion.

Additionally, L-DOPA, co-administered with a peripheral DDCI, has been investigated as a potential treatment for restless leg syndrome (RLS). Unfortunately, however, studies have demonstrated "no clear picture of reduced symptoms".

Dietary supplements

Herbal supplements containing standardized dosages of L-DOPA are available without a prescription. These supplements have recently increased in both availability and popularity in the United Statesmarker (U.S.) and on the internet. The most common plant source of L-DOPA marketed in this manner is Mucuna pruriens (Velvet Bean).

Epigallocatechin gallate (EGCG), found in Camellia sinensis (Tea Plant, also known as Black, White, Oolong, Pu-erh, or Green Tea), is purportedly a natural and potent DDCI, though it is unknown as to whether it is selectively peripheral and not also central in action.

Biological role

Biosynthesis of dopamine

L-DOPA is produced from the amino acid L-tyrosine by the enzyme tyrosine hydroxylase (TH). 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.

L-DOPA can be directly metabolized by catechol-O-methyl transferase (COMT) to 3-O-methyldopa (3-OMD), and then further to vanillactic acid (VLA). This metabolic pathway is non-existent in the healthy body, but becomes important after peripheral L-DOPA administration in patients with PD or in the rare cases of patients with aromatic L-amino acid decarboxylase (AADC) enzyme deficiency.

The prefix L- references its property of levorotation (compared with dextrorotation or D-DOPA).

Notably, L-phenylalanine, L-tyrosine, and L-DOPA, are all are 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.

Side effects

The side effects of L-DOPA may include:

Although there are many adverse effects associated with L-DOPA, particularly psychiatric ones, it has fewer than other antiparkinsonian agents, such as anticholinergics and dopamine receptor agonists.

More serious are the effects of chronic levodopa administration, which include:

  • End-of-dose deterioration of function
  • On/off oscillations
  • Freezing during movement
  • Dose failure (drug resistance)
  • Dyskinesia at peak dose
  • Recent studies have demonstrated that use of L-DOPA without simultaneously giving proper levels of serotonin precursors depletes serotonin
  • The long term use of L-DOPA in PD has been linked to the so called dopamine dysregulation syndrome.

Clinicians will try to avoid these side effects by limiting L-DOPA doses as much as possible until absolutely necessary.


Some scientific studies suggest a cytotoxic role in the promotion and occurrence of adverse effects associated with L-DOPA treatment. Though the drug is generally safe in humans, some researchers have reported an increase in cytotoxicity markers in rat pheochromocytoma PC12 cell lines treated with L-DOPA. Other authors have attributed the observed toxic effects of L-DOPA in neural dopamine cell lines to enhanced formation of quinones through increased auto-oxidation and subsequent cell death in mesencephalic cell cultures. Though L-DOPA is generally considered safe, some controversy surrounds its use in the treatment of PD, given some data indicating a deleterious effect on intracellular and neuronal tissue involved in the pathogenesis of the disease.


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 Parkinsonian symptoms would cause a reduction in their intensity. This treatment was later extended to manganese poisoning and later Parkinsonism by George Cotzias and his coworkers , who greatly increased the dose. The neurologist Oliver Sacks describes this treatment in human patients with encephalitis lethargica in his book Awakenings, upon which the movie of the same name is based.

The 2001 Nobel Prize in Chemistry was also related to L-DOPA: the Nobel Committee awarded one-fourth 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:

Marine adhesion

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.

See also

  • D-DOPA (Dextrodopa)
  • L-DOPS (Droxidopa)
  • Methyldopa (Aldomet, Apo-Methyldopa, Dopamet, Novomedopa, etc)
  • Dopamine (Intropan, Inovan, Revivan, Rivimine, Dopastat, Dynatra, etc)
  • Norepinephrine (Noradrenaline; Levophed, etc)
  • Epinephrine (Adrenaline; Adrenalin, EpiPed, Twinject, etc)


  1. Cotzias GC, Papavasiliou PS, Gellene R. N Engl J Med. 1969 Jul 31;281(5):272. L-dopa in parkinson's syndrome. PMID 5791298

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