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-DOPA, also known as levodopa and -3,4-dihydroxyphenylalanine, is an amino acid that is made and used as part of the normal
biology Biology is the scientific study of life. It is a natural science with a broad scope but has several unifying themes that tie it together as a single, coherent field. For instance, all organisms are made up of cells that process hereditary ...
of some plants and animals, including humans. Humans, as well as a portion of the other animals that utilize -DOPA, make it via
biosynthesis Biosynthesis is a multi-step, enzyme-catalyzed process where substrates are converted into more complex products in living organisms. In biosynthesis, simple compounds are modified, converted into other compounds, or joined to form macromolecul ...
from the
amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha ...
-tyrosine. -DOPA is the
precursor Precursor or Precursors may refer to: * Precursor (religion), a forerunner, predecessor ** The Precursor, John the Baptist Science and technology * Precursor (bird), a hypothesized genus of fossil birds that was composed of fossilized parts of u ...
to the
neurotransmitter A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a synapse. The cell receiving the signal, any main body part or target cell, may be another neuron, but could also be a gland or muscle cell. Neu ...
s
dopamine Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic chemical of the catecholamine and phenethylamine families. Dopamine constitutes about 80% o ...
,
norepinephrine Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic chemical in the catecholamine family that functions in the brain and body as both a hormone and neurotransmitter. The name "noradrenaline" (from Latin '' ad ...
(noradrenaline), and
epinephrine Adrenaline, also known as epinephrine, is a hormone and medication which is involved in regulating visceral functions (e.g., respiration). It appears as a white microcrystalline granule. Adrenaline is normally produced by the adrenal glands and ...
(adrenaline), which are collectively known as
catecholamine A catecholamine (; abbreviated CA) is a monoamine neurotransmitter, an organic compound that has a catechol (benzene with two hydroxyl side groups next to each other) and a side-chain amine. Catechol can be either a free molecule or a su ...
s. Furthermore, -DOPA itself mediates neurotrophic factor release by the brain and CNS. -DOPA can be manufactured and in its pure form is sold as a
psychoactive drug A psychoactive drug, psychopharmaceutical, psychoactive agent or psychotropic drug is a chemical substance, that changes functions of the nervous system, and results in alterations in perception, mood, consciousness, cognition or behavior. ...
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 Parkinson's disease (PD), or simply Parkinson's, is a long-term degenerative disorder of the central nervous system that mainly affects the motor system. The symptoms usually emerge slowly, and as the disease worsens, non-motor symptoms beco ...
and dopamine-responsive dystonia. -DOPA has a counterpart with opposite
chirality Chirality is a property of asymmetry important in several branches of science. The word ''chirality'' is derived from the Greek (''kheir''), "hand", a familiar chiral object. An object or a system is ''chiral'' if it is distinguishable from ...
, -DOPA. As is true for many molecules, the human body produces only one of these
isomer In chemistry, isomers are molecules or polyatomic ions with identical molecular formulae – that is, same number of atoms of each element – but distinct arrangements of atoms in space. Isomerism is existence or possibility of isomers. Is ...
s (the -DOPA form). The enantiomeric purity of -DOPA may be analyzed by determination of the optical rotation or by chiral thin-layer chromatography.


Medical use

-DOPA crosses the protective
blood–brain barrier The blood–brain barrier (BBB) is a highly selective semipermeable border of endothelial cells that prevents solutes in the circulating blood from ''non-selectively'' crossing into the extracellular fluid of the central nervous system where ne ...
, whereas
dopamine Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic chemical of the catecholamine and phenethylamine families. Dopamine constitutes about 80% o ...
itself cannot. Thus, -DOPA is used to increase dopamine concentrations in the treatment of
Parkinson's disease Parkinson's disease (PD), or simply Parkinson's, is a long-term degenerative disorder of the central nervous system that mainly affects the motor system. The symptoms usually emerge slowly, and as the disease worsens, non-motor symptoms beco ...
,
Parkinsonism Parkinsonism is a clinical syndrome characterized by tremor, bradykinesia (slowed movements), rigidity, and postural instability. These are the four motor symptoms found in Parkinson's disease (PD), after which it is named, dementia with Lew ...
, dopamine-responsive dystonia and
Parkinson-plus syndrome Parkinson-plus syndromes (PPS) are a group of neurodegenerative diseases featuring the classical features of Parkinson's disease (tremor, rigidity, akinesia/bradykinesia, and postural instability) with additional features that distinguish them fr ...
. The therapeutic efficacy is different for different kinds of symptoms. Bradykinesia and rigidity are the most responsive symptoms while
tremor A tremor is an involuntary, somewhat rhythmic, muscle contraction and relaxation involving oscillations or twitching movements of one or more body parts. It is the most common of all involuntary movements and can affect the hands, arms, eyes, f ...
s are less responsive to levodopa therapy. Speech, swallowing disorders, postural instability and freezing gait are the least responsive symptoms. Once -DOPA has entered the
central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all p ...
, it is converted into dopamine by the
enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products ...
aromatic -amino acid decarboxylase, also known as DOPA decarboxylase.
Pyridoxal phosphate Pyridoxal phosphate (PLP, pyridoxal 5'- phosphate, P5P), the active form of vitamin B6, is a coenzyme in a variety of enzymatic reactions. The International Union of Biochemistry and Molecular Biology has catalogued more than 140 PLP-dependent ...
( vitamin B6) is a required cofactor in this reaction, and may occasionally be administered along with -DOPA, usually in the
form Form is the shape, visual appearance, or configuration of an object. In a wider sense, the form is the way something happens. Form also refers to: *Form (document), a document (printed or electronic) with spaces in which to write or enter data * ...
of
pyridoxine Pyridoxine, is a form of vitamin B6 found commonly in food and used as a dietary supplement. As a supplement it is used to treat and prevent pyridoxine deficiency, sideroblastic anaemia, pyridoxine-dependent epilepsy, certain metabolic disor ...
. Because levodopa bypasses the enzyme
tyrosine hydroxylase Tyrosine hydroxylase or tyrosine 3-monooxygenase is the enzyme responsible for catalyzing the conversion of the amino acid L-tyrosine to L-3,4-dihydroxyphenylalanine (L-DOPA). It does so using molecular oxygen (O2), as well as iron (Fe2+) and t ...
, 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 -DOPA to dopamine does not only occur within the
central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all p ...
. Cells in the
peripheral nervous system The peripheral nervous system (PNS) is one of two components that make up the nervous system of bilateral animals, with the other part being the central nervous system (CNS). The PNS consists of nerves and ganglia, which lie outside the brai ...
perform the same task. Thus administering -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 effect In medicine, a side effect is an effect, whether therapeutic or adverse, that is secondary to the one intended; although the term is predominantly employed to describe adverse effects, it can also apply to beneficial, but unintended, consequence ...
s seen with sole L-DOPA administration. To bypass these effects, it is standard clinical practice to coadminister (with -DOPA) a peripheral DOPA decarboxylase inhibitor (DDCI) such as
carbidopa Carbidopa (Lodosyn) is a drug given to people with Parkinson's disease in order to inhibit peripheral metabolism of levodopa. This property is significant in that it allows a greater proportion of administered levodopa to cross the blood–br ...
(medicines containing carbidopa, either alone or in combination with -DOPA, are branded as Lodosyn ( Aton Pharma) Sinemet ( Merck Sharp & Dohme Limited), Pharmacopa (
Jazz Pharmaceuticals Jazz Pharmaceuticals plc (a merger of Jazz Pharmaceuticals, Inc. and Azur Pharma plc) is a biopharmaceutical company based in Ireland. It was founded in 2003. One of the company's considerable products is the United States Food and Drug Admini ...
), Atamet ( UCB), Syndopa and Stalevo ( Orion Corporation) or with a
benserazide Benserazide (also called Serazide or Ro 4-4602) is a peripherally acting aromatic L-amino acid decarboxylase or DOPA decarboxylase inhibitor, which is unable to cross the blood–brain barrier. It is on the World Health Organization's List of ...
(combination medicines are branded Madopar or Prolopa), to prevent the peripheral synthesis of dopamine from -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 Carbidopa/levodopa, also known as levocarb and co-careldopa, is the combination of the two medications carbidopa and levodopa. It is primarily used to manage the symptoms of Parkinson's disease, but it does not slow down the disease or stop it ...
. It was approved by the United States
Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...
on December 21, 2018, and is marketed by
Acorda Therapeutics Acorda Therapeutics, Inc. is an American biotechnology company based in Pearl River, New York. The company develops therapies that improve neurological function in people with Parkinson's disease, multiple sclerosis and other neurological disorder ...
. Coadministration of
pyridoxine Pyridoxine, is a form of vitamin B6 found commonly in food and used as a dietary supplement. As a supplement it is used to treat and prevent pyridoxine deficiency, sideroblastic anaemia, pyridoxine-dependent epilepsy, certain metabolic disor ...
without a DDCI accelerates the peripheral
decarboxylation Decarboxylation is a chemical reaction that removes a carboxyl group and releases carbon dioxide (CO2). Usually, decarboxylation refers to a reaction of carboxylic acids, removing a carbon atom from a carbon chain. The reverse process, which is ...
of -DOPA to such an extent that it negates the effects of -DOPA administration, a phenomenon that historically caused great confusion. In addition, -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 -DOPA are: * 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 Protein fosB, also known as FosB and G0/G1 switch regulatory protein 3 (G0S3), is a protein that in humans is encoded by the FBJ murine osteosarcoma viral oncogene homolog B (''FOSB'') gene. The FOS gene family consists of four members: FOS, F ...
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.


Biological role

-DOPA is produced from the amino acid -
tyrosine -Tyrosine or tyrosine (symbol Tyr or Y) or 4-hydroxyphenylalanine is one of the 20 standard amino acids that are used by cells to synthesize proteins. It is a non-essential amino acid with a polar side group. The word "tyrosine" is from the G ...
by the enzyme
tyrosine hydroxylase Tyrosine hydroxylase or tyrosine 3-monooxygenase is the enzyme responsible for catalyzing the conversion of the amino acid L-tyrosine to L-3,4-dihydroxyphenylalanine (L-DOPA). It does so using molecular oxygen (O2), as well as iron (Fe2+) and t ...
. -DOPA can act as an -tyrosine mimetic and be incorporated into proteins by mammalian cells in place of L-tyrosine, generating
protease A protease (also called a peptidase, proteinase, or proteolytic enzyme) is an enzyme that catalyzes (increases reaction rate or "speeds up") proteolysis, breaking down proteins into smaller polypeptides or single amino acids, and spurring the ...
-resistant and aggregate-prone proteins ''in vitro'' and may contribute to neurotoxicity with chronic -DOPA administration. It is also the precursor for the
monoamine Monoamine neurotransmitters are neurotransmitters and neuromodulators that contain one amino group connected to an aromatic ring by a two-carbon chain (such as -CH2-CH2-). Examples are dopamine, norepinephrine and serotonin. All monoamines ar ...
or
catecholamine A catecholamine (; abbreviated CA) is a monoamine neurotransmitter, an organic compound that has a catechol (benzene with two hydroxyl side groups next to each other) and a side-chain amine. Catechol can be either a free molecule or a su ...
neurotransmitters dopamine, norepinephrine (noradrenaline), and epinephrine (adrenaline). Dopamine is formed by the decarboxylation of -DOPA by aromatic -amino acid decarboxylase (AADC). -DOPA can be directly metabolized by catechol-''O''-methyl transferase to 3-''O''-methyldopa, and then further to vanillactic acid. This metabolic pathway is nonexistent in the healthy body, but becomes important after peripheral -DOPA administration in patients with Parkinson's disease or in the rare cases of patients with AADC enzyme deficiency. -Phenylalanine, -tyrosine, and -DOPA are all precursors to the biological
pigment A pigment is a colored material that is completely or nearly insoluble in water. In contrast, dyes are typically soluble, at least at some stage in their use. Generally dyes are often organic compounds whereas pigments are often inorganic compou ...
melanin Melanin (; from el, μέλας, melas, black, dark) is a broad term for a group of natural pigments found in most organisms. Eumelanin is produced through a multistage chemical process known as melanogenesis, where the oxidation of the amino ...
. The enzyme
tyrosinase Tyrosinase is an oxidase that is the rate-limiting enzyme for controlling the production of melanin. The enzyme is mainly involved in two distinct reactions of melanin synthesis otherwise known as the Raper Mason pathway. Firstly, the hydroxy ...
catalyzes the
oxidation Redox (reduction–oxidation, , ) is a type of chemical reaction in which the oxidation states of substrate change. Oxidation is the loss of electrons or an increase in the oxidation state, while reduction is the gain of electrons or ...
of -DOPA to the reactive intermediate
dopaquinone -Dopaquinone also known as ''o''-dopaquinone is a metabolite of L-DOPA (L-dihydroxyphenylalanine) and a precursor of melanin. Biosynthesis of melanin occurs in melanocytes, where tyrosine -Tyrosine or tyrosine (symbol Tyr or Y) or 4-hydroxyph ...
, which reacts further, eventually leading to melanin
oligomer In chemistry and biochemistry, an oligomer () is a molecule that consists of a few repeating units which could be derived, actually or conceptually, from smaller molecules, monomers.Quote: ''Oligomer molecule: A molecule of intermediate relati ...
s. In addition,
tyrosinase Tyrosinase is an oxidase that is the rate-limiting enzyme for controlling the production of melanin. The enzyme is mainly involved in two distinct reactions of melanin synthesis otherwise known as the Raper Mason pathway. Firstly, the hydroxy ...
can convert tyrosine directly to -DOPA in the presence of a reducing agent such as
ascorbic acid Vitamin C (also known as ascorbic acid and ascorbate) is a water-soluble vitamin found in citrus and other fruits and vegetables, also sold as a dietary supplement and as a topical 'serum' ingredient to treat melasma (dark pigment spots) ...
.


Marine adhesion

-DOPA is a key compound in the formation of marine adhesive proteins, such as those found in
mussel Mussel () is the common name used for members of several families of bivalve molluscs, from saltwater and freshwater habitats. These groups have in common a shell whose outline is elongated and asymmetrical compared with other edible clams, which ...
s. 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. 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.


Side effects and adverse reactions

The side effects of -DOPA may include: *
Hypertension Hypertension (HTN or HT), also known as high blood pressure (HBP), is a long-term medical condition in which the blood pressure in the arteries is persistently elevated. High blood pressure usually does not cause symptoms. Long-term high b ...
, especially if the dosage is too high *
Arrhythmia Arrhythmias, also known as cardiac arrhythmias, heart arrhythmias, or dysrhythmias, are irregularities in the heartbeat, including when it is too fast or too slow. A resting heart rate that is too fast – above 100 beats per minute in adult ...
s, although these are uncommon *
Nausea Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. While not painful, it can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of th ...
, which is often reduced by taking the drug with food, although
protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...
reduces drug absorption. -DOPA is an amino acid, so protein competitively inhibits -DOPA absorption. * Gastrointestinal bleeding * Disturbed
respiration Respiration may refer to: Biology * Cellular respiration, the process in which nutrients are converted into useful energy in a cell ** Anaerobic respiration, cellular respiration without oxygen ** Maintenance respiration, the amount of cellul ...
, which is not always harmful, and can actually benefit patients with upper airway obstruction *
Hair loss Hair loss, also known as alopecia or baldness, refers to a loss of hair from part of the head or body. Typically at least the head is involved. The severity of hair loss can vary from a small area to the entire body. Inflammation or scar ...
*
Disorientation Orientation is a function of the mind involving awareness of three dimensions: time, place and person. Problems with orientation lead to ''dis''orientation, and can be due to various conditions, from delirium to intoxication. Typically, disorient ...
and
confusion In medicine, confusion is the quality or state of being bewildered or unclear. The term "acute mental confusion"
* Extreme
emotion Emotions are mental states brought on by neurophysiological changes, variously associated with thoughts, feelings, behavioral responses, and a degree of pleasure or displeasure. There is currently no scientific consensus on a definitio ...
al states, particularly
anxiety Anxiety is an emotion which is characterized by an unpleasant state of inner turmoil and includes feelings of dread over anticipated events. Anxiety is different than fear in that the former is defined as the anticipation of a future threat wh ...
, but also excessive
libido Libido (; colloquial: sex drive) is a person's overall sexual drive or desire for sexual activity. Libido is influenced by biological, psychological, and social factors. Biologically, the sex hormones and associated neurotransmitters that act u ...
* Vivid
dream A dream is a succession of images, ideas, emotions, and sensations that usually occur involuntarily in the mind during certain stages of sleep. Humans spend about two hours dreaming per night, and each dream lasts around 5 to 20 minutes, althou ...
s or
insomnia Insomnia, also known as sleeplessness, is a sleep disorder in which people have trouble sleeping. They may have difficulty falling asleep, or staying asleep as long as desired. Insomnia is typically followed by daytime sleepiness, low energy, ...
* Auditory or visual hallucinations * Effects on learning; some evidence indicates it improves
working memory Working memory is a cognitive system with a limited capacity that can hold information temporarily. It is important for reasoning and the guidance of decision-making and behavior. Working memory is often used synonymously with short-term memory, ...
, while impairing other complex functions *
Somnolence Somnolence (alternatively sleepiness or drowsiness) is a state of strong desire for sleep, or sleeping for unusually long periods (compare hypersomnia). It has distinct meanings and causes. It can refer to the usual state preceding falling asleep ...
and
narcolepsy Narcolepsy is a long-term neurological disorder that involves a decreased ability to regulate sleep–wake cycles. Symptoms often include periods of excessive daytime sleepiness and brief involuntary sleep episodes. About 70% of those affect ...
* A condition similar to
stimulant psychosis Stimulant psychosis is a mental disorder characterized by psychotic symptoms (such as hallucinations, paranoid ideation, delusions, disorganized thinking, grossly disorganized behaviour) which involves and typically occurs following an overdose ...
Although many adverse effects are associated with -DOPA, in particular psychiatric ones, it has fewer than other antiparkinsonian agents, such as
anticholinergic Anticholinergics (anticholinergic agents) are substances that block the action of the neurotransmitter called acetylcholine (ACh) at synapses in the central and peripheral nervous system. These agents inhibit the parasympathetic nervous sys ...
s and dopamine receptor agonists. More serious are the effects of chronic -DOPA administration in the treatment of Parkinson's disease, which include: * End-of-dose deterioration of function * "On/off" oscillations * Freezing during movement * Dose failure (
drug resistance Drug resistance is the reduction in effectiveness of a medication such as an antimicrobial or an antineoplastic in treating a disease or condition. The term is used in the context of resistance that pathogens or cancers have "acquired", that is ...
) *
Dyskinesia Dyskinesia refers to a category of movement disorders that are characterized by involuntary muscle movements, including movements similar to tics or chorea and diminished voluntary movements. Dyskinesia can be anything from a slight tremor of ...
at peak dose ( levodopa-induced dyskinesia) * Possible dopamine dysregulation: The long-term use of -DOPA in Parkinson's disease has been linked to the so-called
dopamine dysregulation syndrome Dopamine dysregulation syndrome (DDS) is a dysfunction of the reward system observed in some individuals taking dopaminergic medications for an extended length of time. It typically occurs in people with Parkinson's disease (PD) who have taken d ...
. Clinicians try to avoid these side effects and adverse reactions by limiting -DOPA doses as much as possible until absolutely necessary. The long term use of L-Dopa increases oxidative stress through
monoamine oxidase Monoamine oxidases (MAO) () are a family of enzymes that catalyze the oxidation of monoamines, employing oxygen to clip off their amine group. They are found bound to the outer membrane of mitochondria in most cell types of the body. The firs ...
led enzymatic degradation of synthesized dopamine causing neuronal damage and cytotoxicity. The oxidative stress is caused by the formation of
reactive oxygen species In chemistry, reactive oxygen species (ROS) are highly reactive chemicals formed from diatomic oxygen (). Examples of ROS include peroxides, superoxide, hydroxyl radical, singlet oxygen, and alpha-oxygen. The reduction of molecular oxygen () p ...
(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, which is capable of pairing with adenosine during
mitosis In cell biology, mitosis () is a part of the cell cycle in which replicated chromosomes are separated into two new nuclei. Cell division by mitosis gives rise to genetically identical cells in which the total number of chromosomes is maintai ...
.


History

In work that earned him a
Nobel Prize The Nobel Prizes ( ; sv, Nobelpriset ; no, Nobelprisen ) are five separate prizes that, according to Alfred Nobel's will of 1895, are awarded to "those who, during the preceding year, have conferred the greatest benefit to humankind." Alfr ...
in 2000, Swedish scientist
Arvid Carlsson Arvid Carlsson (25 January 1923 – 29 June 2018) was a Swedish neuropharmacologist who is best known for his work with the neurotransmitter dopamine and its effects in Parkinson's disease. For his work on dopamine, Carlsson was awarded the Nob ...
first showed in the 1950s that administering -DOPA to animals with drug-induced (
reserpine Reserpine is a drug that is used for the treatment of high blood pressure, usually in combination with a thiazide diuretic or vasodilator. Large clinical trials have shown that combined treatment with reserpine plus a thiazide diuretic reduces ...
) Parkinsonian
symptom Signs and symptoms are the observed or detectable signs, and experienced symptoms of an illness, injury, or condition. A sign for example may be a higher or lower temperature than normal, raised or lowered blood pressure or an abnormality showi ...
s caused a reduction in the intensity of the animals' symptoms. In 1960/61
Oleh Hornykiewicz Oleh Hornykiewicz (17 November 1926 - 26 May 2020) was an Austrian biochemist. Life Oleh Hornykiewicz was born in 1926 in Sykhiw (a district of Lviv), then in Poland (now Ukraine). In 1951, he received his M.D. degree from the University of Vie ...
, after discovering greatly reduced levels of dopamine in autopsied brains of patients with Parkinson's disease, published together with the neurologist
Walther Birkmayer Walther is a masculine given name and a surname. It is a German form of Walter, which is derived from the Old High German ''Walthari'', containing the elements ''wald'' -"power", "brightness" or "forest" and ''hari'' -"warrior". The name was fi ...
dramatic therapeutic antiparkinson effects of intravenously administered -DOPA in patients. This treatment was later extended to manganese poisoning and later Parkinsonism by
George Cotzias George Constantin Cotzias (June 16, 1918 – June 13, 1977) was a Greeks, Greek scientist who together with his coworkers developed L-Dopa treatment, currently the most commonly used treatment for Parkinson's disease. Cotzias was born in Chania ...
and his coworkers, who used greatly increased oral doses, for which they won the 1969
Lasker Prize The Lasker Awards have been awarded annually since 1945 to living persons who have made major contributions to medical science or who have performed public service on behalf of medicine. They are administered by the Lasker Foundation, which was f ...
. The
neurologist Neurology (from el, νεῦρον (neûron), "string, nerve" and the suffix -logia, "study of") is the branch of medicine dealing with the diagnosis and treatment of all categories of conditions and disease involving the brain, the spinal c ...
Oliver Sacks Oliver Wolf Sacks, (9 July 1933 – 30 August 2015) was a British neurologist, naturalist, historian of science, and writer. Born in Britain, Sacks received his medical degree in 1958 from The Queen's College, Oxford, before moving to the Uni ...
describes this treatment in human patients with
encephalitis lethargica Encephalitis lethargica is an atypical form of encephalitis. Also known as "sleeping sickness" or "sleepy sickness" (distinct from tsetse fly-transmitted sleeping sickness), it was first described in 1917 by neurologist Constantin von Econom ...
in his 1973 book ''
Awakenings ''Awakenings'' is a 1990 American drama film directed by Penny Marshall. It is written by Steven Zaillian, who based his screenplay on Oliver Sacks's 1973 memoir '' Awakenings''. It tells the story of neurologist Dr. Malcolm Sayer (Robin Willia ...
'', upon which 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. The 2001
Nobel Prize in Chemistry ) , image = Nobel Prize.png , alt = A golden medallion with an embossed image of a bearded man facing left in profile. To the left of the man is the text "ALFR•" then "NOBEL", and on the right, the text (smaller) "NAT•" then "M ...
was also related to -DOPA: the Nobel Committee awarded one-quarter of the prize to
William S. Knowles William Standish Knowles (June 1, 1917 – June 13, 2012) was an American chemist. He was born in Taunton, Massachusetts. Knowles was one of the recipients of the 2001 Nobel Prize in Chemistry. He split half the prize with Ryōji Noyori for the ...
for his work on chirally catalysed
hydrogenation Hydrogenation is a chemical reaction between molecular hydrogen (H2) and another compound or element, usually in the presence of a catalyst such as nickel, palladium or platinum. The process is commonly employed to reduce or saturate organic ...
reactions, the most noted example of which was used for the synthesis of -DOPA. :


Research


Age-related macular degeneration

In 2015, a retrospective analysis comparing the incidence of
age-related macular degeneration Macular degeneration, also known as age-related macular degeneration (AMD or ARMD), is a medical condition which may result in blurred or no vision in the center of the visual field. Early on there are often no symptoms. Over time, however, som ...
(AMD) between patients taking versus not taking -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.


See also

* -DOPA (Dextrodopa) * -DOPS (Droxidopa) *
Methyldopa Methyldopa, sold under the brand name Aldomet among others, is a medication used for high blood pressure. It is one of the preferred treatments for high blood pressure in pregnancy. For other types of high blood pressure including very high bl ...
(Aldomet, Apo-Methyldopa, Dopamet, Novomedopa, etc.) *
Dopamine Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic chemical of the catecholamine and phenethylamine families. Dopamine constitutes about 80% o ...
(Intropan, Inovan, Revivan, Rivimine, Dopastat, Dynatra, etc.) *
Ciladopa Ciladopa (AY-27,110) is a dopamine agonist with a similar chemical structure to dopamine Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organ ...
*
Neuroleptic malignant syndrome Neuroleptic malignant syndrome (NMS) is a rare but life-threatening reaction that can occur in response to neuroleptic or antipsychotic medication. Symptoms include high fever, confusion, rigid muscles, variable blood pressure, sweating, and fa ...
*
Melanin Melanin (; from el, μέλας, melas, black, dark) is a broad term for a group of natural pigments found in most organisms. Eumelanin is produced through a multistage chemical process known as melanogenesis, where the oxidation of the amino ...
(a metabolite)


References


External links

* {{DEFAULTSORT:DOPA, L- Aromatic amino acids Antiparkinsonian agents Carbonic anhydrase activators Catecholamines Dopamine agonists Prodrugs Monoamine precursors