Levodopa

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Levodopa chemical structure Levodopa
(S)-2-amino-3-(3,4-dihydroxyphenyl) propanoic acid IUPAC name
CAS number 59-92-7	ATC code N04BA01
PubChem 6047	DrugBank APRD00055
Chemical formula	C9H11NO4
Molecular weight	197.19 g/mol
Bioavailability	30%
Metabolism	Aromatic-L-amino-acid decarboxylase
Elimination half-life	0.75–1.5 hours
Excretion	renal 70–80%
Pregnancy category
Legal status	Rx-only
Routes of administration	oral

Levodopa (INN) or L-DOPA (3,4-dihydroxy-L-phenylalanine) is an intermediate in dopamine biosynthesis. Clinically, levodopa is used in the management of Parkinson's disease. Biologically, it is a component in marine adhesives used by pelagic life.

Therapeutic use

Levodopa is used as a prodrug to increase dopamine levels for the treatment of Parkinson's disease, since it is able to cross the blood-brain barrier whereas dopamine itself cannot. Once levodopa has entered the central nervous system (CNS), it is metabolised to dopamine by aromatic-L-amino-acid decarboxylase. However, conversion to dopamine also occurs in the peripheral tissues, causing adverse effects and decreasing the available dopamine to the CNS, so it is standard practice to co-administer a peripheral DOPA decarboxylase inhibitor – carbidopa or benserazide – and often a catechol-O-methyl transferase (COMT) inhibitor.

Adverse effects

Possible adverse drug reactions include:

• Hypotension, especially if the dosage is too high.
• Arrhythmias, although these are uncommon.
• Nausea, which is often helped by taking the drug with food, although protein interferes with drug absorption.
• Gastrointestinal bleeding.
• Disturbed respiration. This is not always harmful, and can actually benefit patients with upper airway obstruction.
• Hair loss.
• Confusion.
• Extreme emotional states, particularly anxiety, but also excessive libido.
• Vivid dreams and/or fragmented sleep.
• Visual and possibly auditory hallucinations.
• Effects on learning. There is some evidence that it improves working memory, while impairing other complex functions.
• Sleepiness and sleep attacks.
• a condition similar to amphetamine psychosis.

Although there are a number of adverse effects associated with levodopa, particularly psychiatric ones, it has fewer than other anti-Parkinson's drugs, including anticholinergics, selegiline, amantadine, and dopamine 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.

Clinicians will try to avoid these by limiting levodopa dosages as far as possible until absolutely necessary.

Biosynthesis

L-DOPA is produced from the amino acid tyrosine by the enzyme tyrosine hydroxylase. It is also the precursor molecule for the catecholamine neurotransmitters dopamine and norepinephrine (noradrenaline), and the hormone epinephrine (adrenaline). Dopamine is formed by the decarboxylation of L-DOPA.

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

History

In work that earned him a Nobel Prize, Swedish scientist Arvid Carlsson first showed in the 1950s that administering levodopa to animals with Parkinsonian symptoms would cause a reduction of the symptoms. The neurologist Oliver Sacks describes this treatment in human patients with encephalitis lethargica in his book Awakenings on 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 uses for the synthesis of L-DOPA.

Adhesion

DOPA is a key molecule 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. DOPA may also be used to prevent surfaces from fouling by bonding antifouling polymers to a susceptible substrate.

Melanin Formation

Both levodopa and the related amino acid tyrosine are precursors to the biological pigment melanin. The enzyme tyrosinase catalyzes the oxidation of either substrate to the reactive intermediate dopaquinone, which reacts further, eventually leading to eumelanin oligomers.

Other research into the effects of Levodopa

Main article: Depression and L-dopa

See also

• Antitremor drugs
• Cholinergic blocking drugs
• DOPA
• Levodopa
• Methyldopa

Books=

Papers

• Goodwin FK, Murphy DL, Brodie HKH, Bunney WE Jr: Levodopa: Alterations in behavior. Clin Pharmacol Ther 12:383-396, 1971.
• Goodwin FK: Psychiatric side effects of levodopa in man. JAMA 218:1915-1920, 1971.

Additional material

Papers

• Waite, J. Herbert, et al. (2005). Mussel Adhesion: Finding the Tricks Worth Mimicking. J Adhesion 81: 1-21.
• Messersmith, Phillip B., et al. (2006). Rapid Gel Formation and Adhesion in Photocurable and Biodegradable Block Copolymers with High DOPA Content. Macromolecules 39: 1740-1748.

External links

• ScienceDaily: Study Reveals Details Of Mussels' Tenacious Bonds (Northwestern University) August 16, 2006

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