Levodopa, also known as
L-DOPA and sold under many brand names, is a
dopaminergic
Dopaminergic means "related to dopamine" (literally, "working on dopamine"), a common neurotransmitter. Dopaminergic substances or actions increase dopamine-related activity in the brain.
Dopaminergic pathways, Dopaminergic brain pathways facil ...
medication
Medication (also called medicament, medicine, pharmaceutical drug, medicinal product, medicinal drug or simply drug) is a drug used to medical diagnosis, diagnose, cure, treat, or preventive medicine, prevent disease. Drug therapy (pharmaco ...
which is used in the treatment of
Parkinson's disease
Parkinson's disease (PD), or simply Parkinson's, is a neurodegenerative disease primarily of the central nervous system, affecting both motor system, motor and non-motor systems. Symptoms typically develop gradually and non-motor issues become ...
(PD) and certain other conditions like
dopamine-responsive dystonia and
restless legs syndrome
Restless legs syndrome (RLS), also known as Willis–Ekbom disease (WED), is a neurological disorder, usually chronic, that causes an overwhelming urge to move one's legs. There is often an unpleasant feeling in the legs that improves temporaril ...
.
The drug is usually used and formulated in combination with a
peripherally selective aromatic L-amino acid decarboxylase (AAAD)
inhibitor
Inhibitor or inhibition may refer to:
Biology
* Enzyme inhibitor, a substance that binds to an enzyme and decreases the enzyme's activity
* Reuptake inhibitor, a substance that increases neurotransmission by blocking the reuptake of a neurotransmi ...
like
carbidopa or
benserazide.
Levodopa is taken
by mouth
Oral administration is a route of administration whereby a substance is taken through the Human mouth, mouth, swallowed, and then processed via the digestive system. This is a common route of administration for many medications.
Oral administ ...
,
by inhalation,
through an intestinal tube, or by
administration into fat (as
foslevodopa).
Side effect
In medicine, a side effect is an effect of the use of a medicinal drug or other treatment, usually adverse but sometimes beneficial, that is unintended. Herbal and traditional medicines also have side effects.
A drug or procedure usually use ...
s of levodopa include
nausea
Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. It can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the throat.
Over 30 d ...
, the wearing-off phenomenon,
dopamine dysregulation syndrome, and
levodopa-induced dyskinesia, among others.
The drug is a
centrally permeable monoamine precursor
Monoamine precursors are precursors of monoamines and monoamine neurotransmitters in the body. The amino acids L-tryptophan and L-5-hydroxytryptophan (5-HTP; oxitriptan) are precursors of serotonin and melatonin, while the amino acids L-pheny ...
and
prodrug
A prodrug is a pharmacologically inactive medication or compound that, after intake, is metabolized (i.e., converted within the body) into a pharmacologically active drug. Instead of administering a drug directly, a corresponding prodrug can be ...
of
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. It is an amine synthesized ...
and hence acts as a
dopamine receptor agonist.
Chemically, levodopa is an
amino acid
Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the 22 α-amino acids incorporated into proteins. Only these 22 a ...
, a
phenethylamine
Phenethylamine (PEA) is an organic compound, natural monoamine alkaloid, and trace amine, which acts as a central nervous system stimulant in humans. In the brain, phenethylamine regulates monoamine neurotransmission by binding to trace ami ...
, and a
catecholamine
A catecholamine (; abbreviated CA), most typically a 3,4-dihydroxyphenethylamine, 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.
Cate ...
.
The major reason for enhanced risks for levodopa induced dyskinesia (LID) and OFF phases during late PD is the progressive dying of nigrostriatal dopaminergic neurons. This results in the conversion of levodopa into dopamine in serotonergic neurons (which cannot re-uptake dopamine and have no proper regulatory capacity for dopamine synthesis) becoming the major dopamine source in the dorsal striatum, leading to the striatal dopamine concentration following the pulsatile oral administration of levodopa with large fluctuations (see the schematic graph figure).
On the other hand, in a disease like
Segawa disease, in which dopamine synthesis is low but without progressive degeneration of dopaminergic neurons, lifelong administration of low doses of levodopa is believed to be without serious side effects.
Levodopa was first
synthesized and isolated in the early 1910s.
The
antiparkinsonian effects of levodopa were discovered in the 1950s and 1960s.
Following this, it was introduced for the treatment of Parkinson's disease in 1970.
Medical uses
Levodopa crosses the protective
blood–brain barrier
The blood–brain barrier (BBB) is a highly selective semipermeable membrane, semipermeable border of endothelium, endothelial cells that regulates the transfer of solutes and chemicals between the circulatory system and the central nervous system ...
, 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. It is an amine synthesized ...
itself cannot.
Thus, levodopa is used to increase dopamine concentrations in the treatment of
Parkinson's disease
Parkinson's disease (PD), or simply Parkinson's, is a neurodegenerative disease primarily of the central nervous system, affecting both motor system, motor and non-motor systems. Symptoms typically develop gradually and non-motor issues become ...
,
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
tremor
A tremor is an involuntary, somewhat rhythmic muscle contraction and relaxation involving neural oscillations, oscillations or twitching movements of one or more body parts. It is the most common of all involuntary movements and can affect the h ...
s are less responsive to levodopa therapy. Speech,
swallowing disorders, postural instability, and freezing gait are the least responsive symptoms.
Once levodopa has entered the
central nervous system
The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain, spinal cord and retina. The CNS is so named because the brain integrates the received information and coordinates and influences the activity o ...
, it is converted into dopamine by the
enzyme
An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...
aromatic -amino acid decarboxylase (AAAD), also known as
DOPA decarboxylase
Aromatic L-amino acid decarboxylase (AADC or AAAD), also known as DOPA decarboxylase (DDC), tryptophan decarboxylase, and 5-hydroxytryptophan decarboxylase, is a lyase enzyme (), located in region 7p12.2-p12.1.
Mechanism
The enzyme uses pyri ...
(DDC).
Pyridoxal phosphate (
vitamin B6) is a required
cofactor in this
reaction
Reaction may refer to a process or to a response to an action, event, or exposure.
Physics and chemistry
*Chemical reaction
*Nuclear reaction
*Reaction (physics), as defined by Newton's third law
* Chain reaction (disambiguation)
Biology and ...
, and may occasionally be administered along with levodopa, usually in the
form of
pyridoxine
Pyridoxine (PN) 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 metaboli ...
. 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 ...
, 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 levodopa 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, spinal cord and retina. The CNS is so named because the brain integrates the received information and coordinates and influences the activity o ...
. Cells in the
peripheral nervous system
The peripheral nervous system (PNS) is one of two components that make up the nervous system of Bilateria, bilateral animals, with the other part being the central nervous system (CNS). The PNS consists of nerves and ganglia, which lie outside t ...
perform the same task. Thus administering levodopa 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 of the use of a medicinal drug or other treatment, usually adverse but sometimes beneficial, that is unintended. Herbal and traditional medicines also have side effects.
A drug or procedure usually use ...
s seen with sole levodopa administration. To bypass these effects, it is standard clinical practice to coadminister (with levodopa) a peripheral
DOPA decarboxylase inhibitor (DDCI) such as
carbidopa (medicines containing carbidopa, either alone or in combination with levodopa, 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 levodopa). However, when consumed as a botanical extract, for example from ''M pruriens'' supplements, a peripheral
DOPA decarboxylase inhibitor is not present.
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 US
Food and Drug Administration
The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respo ...
(FDA) on 21 December 2018, and is marketed by
Acorda Therapeutics.
Coadministration of
pyridoxine
Pyridoxine (PN) 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 metaboli ...
without a DDCI accelerates the peripheral
decarboxylation of levodopa to such an extent that it negates the effects of levodopa administration, a phenomenon that historically caused great confusion.
In addition, levodopa, 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 levodopa 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 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.
Available forms
Levodopa is available, alone or in
combination
In mathematics, a combination is a selection of items from a set that has distinct members, such that the order of selection does not matter (unlike permutations). For example, given three fruits, say an apple, an orange and a pear, there are ...
with
carbidopa, in the form of
immediate-release oral
The word oral may refer to:
Relating to the mouth
* Relating to the mouth, the first portion of the alimentary canal that primarily receives food and liquid
**Oral administration of medicines
** Oral examination (also known as an oral exam or ora ...
tablets and
capsules,
extended-release oral tablets and capsules,
orally disintegrating tablets, as a powder for
inhalation
Inhalation (or inspiration) happens when air or other gases enter the lungs.
Inhalation of air
Inhalation of air, as part of the cycle of breathing, is a vital process for all human life. The process is autonomic (though there are exceptions ...
, and as an
enteral suspension or
gel (via
intestinal tube).
In terms of combination formulations, it is available with
carbidopa (as
levodopa/carbidopa), with
benserazide (as
levodopa/benserazide), and with both carbidopa and
entacapone (as
levodopa/carbidopa/entacapone).
In addition to levodopa itself, certain
prodrug
A prodrug is a pharmacologically inactive medication or compound that, after intake, is metabolized (i.e., converted within the body) into a pharmacologically active drug. Instead of administering a drug directly, a corresponding prodrug can be ...
s of levodopa are available, including
melevodopa (
melevodopa/carbidopa) (used orally) and
foslevodopa (
foslevodopa/foscarbidopa) (used
subcutaneously).
Side effects
The
side effect
In medicine, a side effect is an effect of the use of a medicinal drug or other treatment, usually adverse but sometimes beneficial, that is unintended. Herbal and traditional medicines also have side effects.
A drug or procedure usually use ...
s of levodopa may include:
*
Hypertension
Hypertension, also known as high blood pressure, is a Chronic condition, long-term Disease, medical condition in which the blood pressure in the artery, arteries is persistently elevated. High blood pressure usually does not cause symptoms i ...
, especially if the dosage is too high
*
Arrhythmia
Arrhythmias, also known as cardiac arrhythmias, are irregularities in the cardiac cycle, heartbeat, including when it is too fast or too slow. Essentially, this is anything but normal sinus rhythm. A resting heart rate that is too fast – ab ...
s, although these are uncommon
*
Nausea
Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. It can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the throat.
Over 30 d ...
, 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 residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...
reduces drug absorption. Levodopa is an amino acid, so protein competitively inhibits levodopa absorption.
* Gastrointestinal bleeding
* Disturbed
respiration, 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 scarring ...
*
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. It ranges from an inability to coherently understand ...
and
confusion
In psychology, confusion is the quality or emotional state of being bewildered or unclear. The term "acute mental confusion"
* Extreme
emotion
Emotions are physical and mental states brought on by neurophysiology, neurophysiological changes, variously associated with thoughts, feelings, behavior, behavioral responses, and a degree of pleasure or suffering, displeasure. There is ...
al states, particularly
anxiety
Anxiety is an emotion characterised by an unpleasant state of inner wikt:turmoil, turmoil and includes feelings of dread over Anticipation, anticipated events. Anxiety is different from fear in that fear is defined as the emotional response ...
, but also excessive
libido
In psychology, libido (; ) is psychic drive or energy, usually conceived of as sexual in nature, but sometimes conceived of as including other forms of desire. The term ''libido'' was originally developed by Sigmund Freud, the pioneering origin ...
* Vivid
dream
A dream is a succession of images, ideas, emotions, and sensation (psychology), 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 ...
s or
insomnia
Insomnia, also known as sleeplessness, is a sleep disorder where people have difficulty sleeping. They may have difficulty falling asleep, or staying asleep for as long as desired. Insomnia is typically followed by daytime sleepiness, low ene ...
*
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 Memory, 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 m ...
, 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 aslee ...
and
narcolepsy
Narcolepsy is a chronic neurological disorder that impairs the ability to regulate sleep–wake cycles, and specifically impacts REM (rapid eye movement) sleep. The symptoms of narcolepsy include excessive daytime sleepiness (EDS), sleep-r ...
* A condition similar to
stimulant psychosis
Stimulant psychosis is a mental disorder characterized by psychotic symptoms such as hallucinations, paranoid ideation, delusions, disorganized thinking, and grossly disorganized behaviour. It typically occurs following an overdose or several ...
Although many adverse effects are associated with levodopa, in particular psychiatric ones, it has fewer than other
antiparkinsonian agent
In the management of Parkinson's disease, due to the chronic nature of Parkinson's disease (PD), a broad-based program is needed that includes patient and family education, support-group services, general wellness maintenance, exercise, and nutr ...
s, such as
anticholinergic
Anticholinergics (anticholinergic agents) are substances that block the action of the acetylcholine (ACh) neurotransmitter at synapses in the central nervous system, central and peripheral nervous system.
These agents inhibit the parasympatheti ...
s and
dopamine receptor agonists.
More serious are the effects of chronic levodopa 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 at peak dose (
levodopa-induced dyskinesia)
* Possible dopamine dysregulation: The long-term use of levodopa in Parkinson's disease has been linked to the so-called
dopamine dysregulation syndrome.
Rapidly decreasing the dose of levodopa can result in
neuroleptic malignant syndrome
Neuroleptic malignant syndrome (NMS) is a rare but life-threatening reaction that can occur in response to antipsychotics (neuroleptic) or other drugs that block the effects of dopamine. Symptoms include high fever, confusion, rigid muscles, va ...
.
Clinicians try to avoid these side effects and adverse reactions by limiting levodopa doses as much as possible until absolutely necessary.
Metabolites of dopamine, such as
DOPAL, are known to be
dopaminergic neurotoxins. The long term use of levodopa 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 fi ...
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 and biology, reactive oxygen species (ROS) are highly Reactivity (chemistry), reactive chemicals formed from diatomic oxygen (), water, and hydrogen peroxide. Some prominent ROS are hydroperoxide (H2O2), superoxide (O2−), hydroxyl ...
(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
Mitosis () is a part of the cell cycle in eukaryote, eukaryotic cells in which replicated chromosomes are separated into two new Cell nucleus, nuclei. Cell division by mitosis is an equational division which gives rise to genetically identic ...
. See also the
catecholaldehyde hypothesis.
Pharmacology
Pharmacodynamics
Levodopa is a
dopamine precursor and
prodrug
A prodrug is a pharmacologically inactive medication or compound that, after intake, is metabolized (i.e., converted within the body) into a pharmacologically active drug. Instead of administering a drug directly, a corresponding prodrug can be ...
of
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. It is an amine synthesized ...
and hence acts as a
non-selective dopamine receptor agonist, including of the
D1-like receptors (
D1,
D5) and the
D2-like receptors (
D2,
D3,
D4).
Pharmacokinetics
The
bioavailability
In pharmacology, bioavailability is a subcategory of absorption and is the fraction (%) of an administered drug that reaches the systemic circulation.
By definition, when a medication is administered intravenously, its bioavailability is 100%. H ...
of levodopa is 30%.
It is
metabolized into
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. It is an amine synthesized ...
by
aromatic--amino-acid decarboxylase (AAAD) in the
central nervous system
The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain, spinal cord and retina. The CNS is so named because the brain integrates the received information and coordinates and influences the activity o ...
and periphery.
The
elimination half-life
Biological half-life (elimination half-life, pharmacological half-life) is the time taken for concentration of a biological substance (such as a medication) to decrease from its maximum concentration ( Cmax) to half of Cmax in the blood plasma. ...
of levodopa is 0.75 to 1.5hours.
It is
excreted 70–80% in
urine
Urine is a liquid by-product of metabolism in humans and many other animals. In placental mammals, urine flows from the Kidney (vertebrates), kidneys through the ureters to the urinary bladder and exits the urethra through the penile meatus (mal ...
.
Chemistry
Levodopa is an
amino acid
Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the 22 α-amino acids incorporated into proteins. Only these 22 a ...
and a
substituted phenethylamine
Substituted phenethylamines (or simply phenethylamines) are a chemical class of organic compounds that are based upon the phenethylamine structure; the class is composed of all the derivative (chemistry), derivative compounds of phenethylamine ...
and
catecholamine
A catecholamine (; abbreviated CA), most typically a 3,4-dihydroxyphenethylamine, 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.
Cate ...
.
Analogues and prodrugs of levodopa include
melevodopa,
etilevodopa,
foslevodopa, and
XP-21279. Some of these, like melevodopa and foslevodopa, are approved for the treatment of
Parkinson's disease
Parkinson's disease (PD), or simply Parkinson's, is a neurodegenerative disease primarily of the central nervous system, affecting both motor system, motor and non-motor systems. Symptoms typically develop gradually and non-motor issues become ...
similarly to levodopa.
Other analogues include
methyldopa, an
antihypertensive agent, and
droxidopa (
L-DOPS), a
norepinephrine precursor and prodrug.
6-Hydroxydopa, a prodrug of
6-hydroxydopamine (6-OHDA), is a
potent dopaminergic neurotoxin used in
scientific research
The scientific method is an empirical method for acquiring knowledge that has been referred to while doing science since at least the 17th century. Historically, it was developed through the centuries from the ancient and medieval world. The ...
.
History
Levodopa was first
synthesized in 1911 by Torquato Torquati from the ''
Vicia faba
''Vicia faba'', commonly known as the broad bean, fava bean, or faba bean, is a species of vetch, a flowering plant in the pea and bean family Fabaceae. It is widely cultivated as a crop for human consumption, and also as a cover crop. Vari ...
'' bean.
It was first isolated in 1913 by Marcus Guggenheim from the ''V.faba'' bean.
Guggenheim tried levodopa at a dose of 2.5mg and thought that it was inactive aside from
nausea
Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. It can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the throat.
Over 30 d ...
and
vomiting
Vomiting (also known as emesis, puking and throwing up) is the forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose.
Vomiting can be the result of ailments like food poisoning, gastroenteritis, pre ...
.
In work that earned him a
Nobel Prize
The Nobel Prizes ( ; ; ) are awards administered by the Nobel Foundation and granted in accordance with the principle of "for the greatest benefit to humankind". The prizes were first awarded in 1901, marking the fifth anniversary of Alfred N ...
in 2000,
Swedish scientist
Arvid Carlsson first showed in the 1950s that administering levodopa to animals with drug-induced (
reserpine
Reserpine is a drug that is used for the treatment of hypertension, 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 diur ...
) Parkinsonian
symptom
Signs and symptoms are diagnostic indications of an illness, injury, or condition.
Signs are objective and externally observable; symptoms are a person's reported subjective experiences.
A sign for example may be a higher or lower temperature ...
s caused a reduction in the intensity of the animals' symptoms. In 1960 or 1961
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 levodopa 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 first study reporting improvements in patients with Parkinson's disease resulting from treatment with levodopa was published in 1968.
Levodopa was first marketed in 1970 by Roche under the brand name Larodopa.
The
neurologist
Neurology (from , "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 nervous system, which comprises the brain, the ...
Oliver Sacks
Oliver Wolf Sacks (9 July 1933 – 30 August 2015) was a British neurology, neurologist, Natural history, naturalist, historian of science, and writer.
Born in London, Sacks received his medical degree in 1958 from The Queen's College, Oxford ...
describes this treatment in human patients with
encephalitis lethargica in his 1973 book ''
Awakenings'', upon which
the 1990 movie of the same name is based.
Carbidopa was added to levodopa in 1974 and this improved its
tolerability.
Society and culture
Names
''Levodopa'' is the
generic name of the drug and its , , , , , , and .
Research
Novel formulations and prodrugs
New levodopa formulations for use by other
routes of administration
In pharmacology and toxicology, a route of administration is the way by which a medication, drug, fluid, poison, or other substance is taken into the body.
Routes of administration are generally classified by the location at which the substance ...
, such as
subcutaneous administration
Subcutaneous administration is the insertion of medications beneath the skin either by injection or infusion.
A subcutaneous injection is administered as a bolus into the subcutis, the layer of skin directly below the dermis and epidermis, colle ...
, are being developed.
Levodopa
prodrug
A prodrug is a pharmacologically inactive medication or compound that, after intake, is metabolized (i.e., converted within the body) into a pharmacologically active drug. Instead of administering a drug directly, a corresponding prodrug can be ...
s, with the potential for better
pharmacokinetics
Pharmacokinetics (from Ancient Greek ''pharmakon'' "drug" and ''kinetikos'' "moving, putting in motion"; see chemical kinetics), sometimes abbreviated as PK, is a branch of pharmacology dedicated to describing how the body affects a specific su ...
, reduced fluctuations in levodopa levels, and reduced "on–off" phenomenon, are being researched and developed.
Depression
Levodopa has been reported to be inconsistently effective as an
antidepressant
Antidepressants are a class of medications used to treat major depressive disorder, anxiety disorders, chronic pain, and addiction.
Common side effects of antidepressants include Xerostomia, dry mouth, weight gain, dizziness, headaches, akathi ...
in the treatment of
depressive disorder
A mood disorder, also known as an affective disorder, is any of a group of conditions of mental disorder, mental and Abnormal behavior, behavioral Disorder (medicine), disorder where the main underlying characteristic is a disturbance in the per ...
s.
However, it was found to enhance psychomotor activation in people with depression.
Motivational disorders
Levodopa has been found to increase the willingness to exert
effort for
rewards in humans and hence appears to show
pro-motivational effects.
Other
dopaminergic agents have also shown pro-motivational effects and may be useful in the treatment of
motivational disorders.
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. Some people experien ...
(AMD) between patients taking versus not taking levodopa found that the drug delayed onset of AMD by around 8years. The authors state that significant effects were obtained for both dry and wet AMD.
References
External links
*
{{Portal bar , Medicine
Alpha-Amino acids
Antiparkinsonian agents
Aromatic amino acids
Carbonic anhydrase activators
Catecholamines
Dopamine agonists
Monoamine precursors
Phenethylamines
Pro-motivational agents
Prodrugs