Levodopa
Systematic (IUPAC) name
(S)-2-amino-3-(3,4-dihydroxyphenyl) propanoic acid
Identifiers
CAS number	59-92-7
ATC code	N04BA01
PubChem	6047
DrugBank	APRD00309
Chemical data
Formula	C9H11NO4
Mol. mass	197. IUPAC Nomenclature is a system of naming Chemical compounds and of describing the science of Chemistry in general CAS registry numbers are unique numerical identifiers for Chemical compounds Polymers biological sequences mixtures and Alloys They are also referred to The Anatomical Therapeutic Chemical Classification System is used for the classification of drugs It is controlled by the WHO Collaborating Centre for Drug A section of the Anatomical Therapeutic Chemical Classification System. PubChem is a Database of chemical Molecules The system is maintained by the National Center for Biotechnology Information (NCBI a component The DrugBank database available at the University of Alberta is a unique Bioinformatics and Cheminformatics resource that combines detailed drug (i A chemical formula is a way of expressing information about the Atoms that constitute a particular Chemical compound, and how the relationship between those atoms changes Carbon (kɑɹbən is a Chemical element with the symbol C and its Atomic number is 6 Hydrogen (ˈhaɪdrədʒən is the Chemical element with Atomic number 1 Nitrogen (ˈnaɪtɹəʤɪn is a Chemical element that has the symbol N and Atomic number 7 and Atomic weight 14 Oxygen (from the Greek roots ὀξύς (oxys (acid literally "sharp" from the taste of acids and -γενής (-genēs (producer literally begetteris the The molecular mass (abbreviated m of a substance, more commonly referred to as molecular weight and abbreviated as MW, is the Mass of one 19 g/mol
Pharmacokinetic data
Bioavailability	30%
Metabolism	Aromatic-L-amino-acid decarboxylase
Half life	0. In Pharmacology, bioavailability is used to describe the fraction of an administered Dose of unchanged drug that reaches the Systemic circulation, one of Drug metabolism is the Metabolism of drugs, their Biochemical modification or degradation usually through specialized enzymatic systems Aromatic L-amino acid decarboxylase ( synonyms DOPA decarboxylase Tryptophan Decarboxylase, 5-hydroxytryptophan decarboxylase AAAD is a Lyase The biological half-life of a substance is the time it takes for a substance (drug radioactive nuclide or other to lose half of its pharmacologic physiologic or radiologic activity 75–1. 5 hours
Excretion	renal 70–80%
Therapeutic considerations
Pregnancy cat.	B3(AU) C(US)
Legal status	OTC
Routes	oral

Levodopa (INN) or L-DOPA (3,4-dihydroxy-L-phenylalanine) is an intermediate in dopamine biosynthesis. Excretion is the process of eliminating waste products of Metabolism and other non-useful materials The kidneys are complicated organs that have numerous biological roles The pregnancy category of a pharmaceutical agent is an assessment of the risk of fetal injury due to the pharmaceutical if it is used as directed by the mother during For a topic outline on this subject see List of basic Australia topics. The United States of America —commonly referred to as the The regulation of therapeutic goods, that is drugs and therapeutic devices, varies by jurisdiction In Pharmacology and Toxicology, a route An International Nonproprietary Name ( INN; also known as rINN, for recommended International Nonproprietary Name or pINN for proposed Hydroxyl in Chemistry stands for a molecule consisting of an Oxygen atom and a Hydrogen atom connected by a Covalent bond. Phe redirects here For the BitTorrent feature see PHE. For the constellation see Phoenix (constellation. Dopamine is a Hormone and Neurotransmitter occurring in a wide variety of animals including both vertebrates and invertebrates Biosynthesis is a phenomenon wherein Chemical compounds are produced from simpler Reagents Biosynthesis unlike Chemosynthesis, takes place within living In clinical use, levodopa is administered in the management of Parkinson's disease. Parkinson's disease (also known as Parkinson disease or PD) is a degenerative disorder of the Central nervous system that often impairs the sufferer's It is also used as a component in marine adhesives used by pelagic life. Any water in the sea that is not close to the bottom is in the pelagic zone.

Contents 1 Therapeutic use 2 Adverse effects 2.1 Toxicity 3 Biosynthesis 4 History 5 Supplements containing L-DOPA 6 Adhesion 7 Melanin formation 8 References 8.1 Footnotes 8.2 General references 9 External links

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. A prodrug is a pharmacological substance ( drug) that is administered in an inactive (or significantly less active form Dopamine is a Hormone and Neurotransmitter occurring in a wide variety of animals including both vertebrates and invertebrates Parkinson's disease (also known as Parkinson disease or PD) is a degenerative disorder of the Central nervous system that often impairs the sufferer's The blood-brain barrier (BBB is a metabolic or cellular structure in the Central nervous system (CNS that restricts the passage of various chemical substances and microscopic Once levodopa has entered the central nervous system (CNS), it is metabolized to dopamine by aromatic L-amino acid decarboxylase. In Vertebrates the central nervous system ( CNS) is the part of the Nervous system which is enclosed in the Meninges. Aromatic L-amino acid decarboxylase ( synonyms DOPA decarboxylase Tryptophan Decarboxylase, 5-hydroxytryptophan decarboxylase AAAD is a Lyase Pyridoxal phosphate (vitamin B6) is a required cofactor for this decarboxylation, and may be administered along with levodopa, usually as pyridoxine. Pyridoxal-phosphate (PLP Pyridoxal -5'- Phosphate, P5P is a Prosthetic group of some Enzymes It is the active form of vitamin B6 Vitamin B6 is a water-soluble Vitamin. Pyridoxal phosphate (PLP is the active form and is a cofactor in many reactions of Amino acid metabolism including

Conversion to dopamine also occurs in the peripheral tissues, i. e. outside the brain. This is the primary mechanism of the adverse effects of levodopa. It is standard clinical practice to co-administer a peripheral DOPA decarboxylase inhibitor—carbidopa or benserazide—and often a catechol-O-methyl transferase (COMT) inhibitor, to prevent synthesis of dopamine in peripheral tissue. Aromatic L-amino acid decarboxylase ( synonyms DOPA decarboxylase Tryptophan Decarboxylase, 5-hydroxytryptophan decarboxylase AAAD is a Lyase Carbidopa (MK-486 tradename Lodosyn) is a drug given to people with Parkinson's disease in order to inhibit peripheral Metabolism of Levodopa Benserazide (also called Serazide or Ro 4-4602 is a DOPA decarboxylase inhibitor which is unable to cross the Blood-brain barrier. Catechol- O -methyl transferase ( COMT;) is one of several Enzymes that degrade Catecholamines such as Dopamine, Epinephrine Co-administration of pyridoxine without a decarboxylase inhibitor accelerates the extracerebral decarboxylation to such an extent that it cancels out the effects of levodopa administration, a circumstance which historically caused great confusion.

Levodopa has also been used for many years as an effective treatment for restless leg syndrome (RLS). Restless legs syndrome (RLS Wittmaack-Ekbom's syndrome, or sometimes but inaccurately referred to as Nocturnal myoclonus) is a condition that is characterized

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, which 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. An adverse drug reaction (abbreviated ADR) or adverse drug event (abbreviated ADE) is an expression that describes the unwanted negative consequences In Physiology and Medicine, hypotension refers to an abnormally low Blood pressure. Dysrhythmia redirects here For the American band see Dysrhythmia (band. Nausea ( Latin: Nausea, Greek:, " Sea-sickness " also called wamble) is the sensation of unease and discomfort Proteins are large Organic compounds made of Amino acids arranged in a linear chain and joined together by Peptide bonds between the Carboxyl In Animal physiology, respiration is the transport of Oxygen from the outside air to the cells within tissues and the transport of Carbon dioxide Baldness involves the state of lacking hair where it often grows especially on the head An emotion is a mental and physiological state associated with a wide variety of feelings thoughts and behaviours Anxiety is a physiological and psychological state characterized by Cognitive, Somatic, Emotional and Behavioral components Libido in its common usage means Sexual desire however more technical definitions such as those found in the work of Carl Jung, are more general referring to libido Dreams are the images sounds thoughts and feelings experienced while Sleeping, particularly strongly associated with Rapid eye movement sleep. A hallucination, in the broadest sense is a Perception in the absence of a stimulus. Working memory (also referred to as Short term memory, depending on the specific theory is a theoretical construct within Cognitive psychology that refers to the Amphetamine psychosis is a form of Psychosis which can result from Amphetamine or Methamphetamine use

Although there are many adverse effects associated with levodopa, particularly psychiatric ones, it has fewer than other anti-Parkinson's drugs, including anticholinergics, amantadine, and dopamine agonists. An anticholinergic agent is a substance that blocks the Neurotransmitter acetylcholine in the central and the Peripheral nervous system. Amantadine is the Organic compound known formally as 1-aminoadamantane A dopamine agonist is a compound that activates Dopamine receptors mimicking the effect of the neurotransmitter Dopamine.

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. Drug resistance is the reduction in effectiveness of a drug in curing a disease or improving a patient's symptoms Dyskinesia refers to involuntary movements similar to a Tic or Chorea.

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

Toxicity

Some studies suggest a cytotoxic role in the promotion and occurrence of adverse effects associated with levodopa treatment. ^[1] 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 levodopa. Cytotoxicity is the quality of being toxic to cells Examples of toxic agents are a Chemical substance, an Immune cell or some types of Venom Rats are various medium sized long-tailed Rodents of the superfamily Muroidea ^[2] Other authors have attributed the observed toxic effects of levodopa in neural dopamine cell lines to enhanced formation of quinones through increased auto-oxidation and subsequent cell death in mesencephalic cell cultures. Toxicity is the degree to which a substance is able to damage an exposed organism Dopamine is a Hormone and Neurotransmitter occurring in a wide variety of animals including both vertebrates and invertebrates "DDQ" redirects here DDQ is also the former callsign of a TV station in Toowoomba Queensland Australia ^[3][4] Though levodopa is generally considered safe, some controversy surrounds use of the drug in Parkinson's Disease given some data indicating a deleterious effect on intracellular and neuronal tissue involved in the pathogenesis of the disease. A drug, broadly speaking is any chemical substance that when absorbed into the body Parkinson's disease (also known as Parkinson disease or PD) is a degenerative disorder of the Central nervous system that often impairs the sufferer's Not to be confused with Intercellular, meaning "between cells" Neurons (ˈnjuːɹɒn also known as neurones and nerve cells) are responsive cells in the Nervous system that process and transmit information The term pathogenesis means step by step development of a disease due to a series of changes in the structure and /or function of a cell/tissue/organ being caused by a microbial, chemical or physical ^[5]

Biosynthesis

L-DOPA is produced from the amino acid tyrosine by the enzyme tyrosine hydroxylase. In Chemistry, an amino acid is a Molecule containing both Amine and Carboxyl Functional groups In Biochemistry, this Tyrosine (abbreviated as Tyr or Y) or 4-hydroxyphenylalanine, is one of the 20 Amino acids that are used by cells to synthesize Tyrosine hydroxylase or tyrosine 3-monooxygenase is the Enzyme responsible for catalyzing the conversion of the Amino acid L-tyrosine to It is also the precursor molecule for the catecholamine neurotransmitters dopamine and norepinephrine (noradrenaline), and the hormone epinephrine (adrenaline). See Chemical synapse for an introduction to concepts and terminology used in this article Dopamine is a Hormone and Neurotransmitter occurring in a wide variety of animals including both vertebrates and invertebrates Norepinephrine ( INN) (abbreviated norepi or NE) or noradrenaline ( BAN) (abbreviated NA or NAd) is a Hormones (from Greek ὁρμή - "impetus" are chemicals released by cells that affect cells in other parts of the body 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). Catechol- O -methyl transferase ( COMT;) is one of several Enzymes that degrade Catecholamines such as Dopamine, Epinephrine This metabolic pathway is non-existent in the healthy body but becomes important after peripheral L-DOPA administration in patients with Parkinson's Disease or in the rare cases of patients with aromatic L-amino acid decarboxylase (AADC) enzyme deficiency. Aromatic L-amino acid decarboxylase ( synonyms DOPA decarboxylase Tryptophan Decarboxylase, 5-hydroxytryptophan decarboxylase AAAD is a Lyase ^[6]

The prefix L- references its property of levorotation (compared with dextrorotation or D-DOPA). Dextrorotation and levorotation (also spelled laevorotation) refer respectively to the properties of rotating plane Polarized light clockwise (for dextrorotation Dextrorotation and levorotation (also spelled laevorotation) refer respectively to the properties of rotating plane Polarized light clockwise (for dextrorotation D-DOPA (Dextrodopa is similar to L-DOPA (levodopa 34-dihydroxy-L-phenylalanine but with opposite chirality.

History

In work that earned him a Nobel Prize in 2000, 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 Nobel Prize in Physiology or Medicine (Nobelpriset i fysiologi eller medicin is awarded once a year by the Swedish Karolinska Institute. Arvid Carlsson (born January 25, 1923) is a Swedish Scientist who is best known for his work with the Neurotransmitter Dopamine 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. Oliver Wolf Sacks, CBE (born July 9, 1933, London is a British Neurologist residing in the United States who has written popular books about Encephalitis lethargica (EL or von Economo disease is an atypical form of Encephalitis. Awakenings ( 1973, rev ed 1990; ISBN 0-375-70405-1 is a non-fiction book by Oliver Sacks that chronicles his efforts in the late Awakenings is a 1990 Drama film based on Oliver Sacks ' memoir of the same name.

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. The Nobel Prize in Chemistry (Nobelpriset i kemi is awarded annually by the Royal Swedish Academy of Sciences to scientists in the various fields of Chemistry. William S Knowles (born June 1, 1917) is an American Chemist. Hydrogenation is the Chemical reaction that results in addition of Hydrogen (H2

Supplements containing L-DOPA

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 States and on the internet. The most common plant source of L-DOPA marketed in this manner is a tropical legume, Mucuna pruriens, also known as "Velvet Bean" and by a number of other common names. A legume is a Plant in the family Fabaceae (or Leguminosae or a Fruit of these specific plants Mucuna pruriens ( Syn Dolichos pruriens) is a tropical legume known by a multitude of Common names (see below

Two of the most popular brands of Mucuna pruriens are "DopaBean," marketed by Solaray, and "Mucuna," marketed by Physician Formulas, Inc. These preparations claim to contain standardized dosages of L-DOPA in enteric-coated capsules. The dosage claimed is usually about 50 mg per capsule, and the recommended dose is two capsules per day. A third product, "L-Dopa," marketed by Unique Nutrition, claims a higher effective dose of 250 mg. American Nutrition also carries a Mucuna pruriens standardized to 40% L-DOPA under its NutraceuticsRx label.

Some of the claims made for the use of these supplements may have validity, whereas many do not. Among the most common claims are that the supplements will increase libido and aid in body-building (presumably by increasing human growth hormone in both cases). Growth hormone ( GH) is a Peptide hormone that stimulates growth and cell reproduction in humans and other animals The long-term consequences of the use of these supplements by healthy individuals remains to be seen.

Adhesion

DOPA is a key molecule in the formation of marine adhesive proteins, such as those found in mussels. Glue or adhesive is a compound that adheres or bonds two items together The common name mussel is used for members of several different families of Clams or Bivalve Molluscs, from both saltwater and freshwater habitats 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 its precursor amino acid L-tyrosine are precursors to the biological pigment melanin. Tyrosine (abbreviated as Tyr or Y) or 4-hydroxyphenylalanine, is one of the 20 Amino acids that are used by cells to synthesize Melanin is a class of compounds found in the Plant, Animal and Protista kingdoms, where it serves predominantly as a Pigment. The enzyme tyrosinase catalyzes the oxidation of L-dopa to the reactive intermediate dopaquinone, which reacts further, eventually leading to melanin oligomers. In Chemistry, an oligomer consists of a limited number of Monomer units (ολιγος or oligos is Greek for "a few" in contrast to a

References

Footnotes

General references

• Waite, J. Herbert, et al. (2005). "Mussel Adhesion: Finding the Tricks Worth Mimicking". J Adhesion 81: 1-21. doi:10.1080/00218460590944602. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document.  
• 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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