Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is an
organic chemical of the catecholamine and phenethylamine families that
plays several important roles in the brain and body. It is an amine
synthesized by removing a carboxyl group from a molecule of its
precursor chemical L-DOPA, which is synthesized in the brain and
Dopamine is also synthesized in plants and most animals. In
the brain, dopamine functions as a neurotransmitter—a chemical
released by neurons (nerve cells) to send signals to other nerve
cells. The brain includes several distinct dopamine pathways, one of
which plays a major role in the motivational component of
reward-motivated behavior. The anticipation of most types of rewards
increase the level of dopamine in the brain, and many addictive
drugs increase dopamine neuronal activity. Other brain dopamine
pathways are involved in motor control and in controlling the release
of various hormones. These pathways and cell groups form a dopamine
system which is neuromodulatory.
In popular culture and media dopamine is often seen as the main
chemical of pleasure, but the current opinion in pharmacology is that
dopamine instead mediates incentive salience which signals the value
of a given reward to the organism and motivating action required for
attainment. In other words, dopamine appears to mediate desire and
motivation moreso than pleasure.
Outside the central nervous system, dopamine functions primarily as a
local chemical messenger. In blood vessels, it inhibits norepinephrine
release and acts as a vasodilator (at normal concentrations); in the
kidneys, it increases sodium excretion and urine output; in the
pancreas, it reduces insulin production; in the digestive system, it
reduces gastrointestinal motility and protects intestinal mucosa; and
in the immune system, it reduces the activity of lymphocytes. With the
exception of the blood vessels, dopamine in each of these peripheral
systems is synthesized locally and exerts its effects near the cells
that release it.
Several important diseases of the nervous system are associated with
dysfunctions of the dopamine system, and some of the key medications
used to treat them work by altering the effects of dopamine.
Parkinson's disease, a degenerative condition causing tremor and motor
impairment, is caused by a loss of dopamine-secreting neurons in an
area of the midbrain called the substantia nigra. Its metabolic
L-DOPA can be manufactured, and in its pure form marketed as
Levodopa is the most widely used treatment for the condition. There is
evidence that schizophrenia involves altered levels of dopamine
activity, and most antipsychotic drugs used to treat this are dopamine
antagonists which reduce dopamine activity. Similar dopamine
antagonist drugs are also some of the most effective anti-nausea
Restless legs syndrome
Restless legs syndrome and attention deficit hyperactivity
disorder (ADHD) are associated with decreased dopamine activity.
Dopaminergic stimulants can be addictive in high doses, but some are
used at lower doses to treat ADHD.
Dopamine itself is available as a
manufactured medication for intravenous injection: although it cannot
reach the brain from the bloodstream, its peripheral effects make it
useful in the treatment of heart failure or shock, especially in
3.1 Cellular effects
3.1.1 Storage, release, and reuptake
3.2 Nervous system
3.2.1 Basal ganglia
3.3 Outside the nervous system
4 Medical uses
5 Disease, disorders, and pharmacology
5.1 Aging brain
5.2 Parkinson's disease
5.3 Drug addiction and psychostimulants
Psychosis and antipsychotic drugs
5.5 Attention deficit hyperactivity disorder
6 Comparative biology and evolution
6.4 As a precursor for melanin
7 History and development
9 External links
A dopamine molecule consists of a catechol structure (a benzene ring
with two hydroxyl side groups) with one amine group attached via an
ethyl chain. As such, dopamine is the simplest possible
catecholamine, a family that also includes the neurotransmitters
norepinephrine and epinephrine. The presence of a benzene ring with
this amine attachment makes it a substituted phenethylamine, a family
that includes numerous psychoactive drugs.
Like most amines, dopamine is an organic base. As a base, it is
generally protonated in acidic environments (in an acid-base
reaction). The protonated form is highly water-soluble and
relatively stable, but can become oxidized if exposed to oxygen or
other oxidants. In basic environments, dopamine is not
protonated. In this free base form, it is less water-soluble and
also more highly reactive. Because of the increased stability and
water-solubility of the protonated form, dopamine is supplied for
chemical or pharmaceutical use as dopamine hydrochloride—that is,
the hydrochloride salt that is created when dopamine is combined with
hydrochloric acid. In dry form, dopamine hydrochloride is a fine
Biosynthetic pathways for catecholamines and trace amines in the human
In humans, catecholamines and phenethylaminergic trace amines are
derived from the amino acid phenylalanine. It is well established that
dopamine is produced from L-tyrosine via L-DOPA; however, recent
evidence has shown that
CYP2D6 is expressed in the human brain and
catalyzes the biosynthesis of dopamine from L-tyrosine via
Dopamine is synthesized in a restricted set of cell types, mainly
neurons and cells in the medulla of the adrenal glands. The
primary and minor metabolic pathways respectively are:
Phenylalanine → L-
Phenylalanine → L-
Tyrosine → p-
Phenylalanine → m-
Tyrosine → m-
The direct precursor of dopamine, L-DOPA, can be synthesized
indirectly from the essential amino acid phenylalanine or directly
from the non-essential amino acid tyrosine. These amino acids are
found in nearly every protein and so are readily available in food,
with tyrosine being the most common. Although dopamine is also found
in many types of food, it is incapable of crossing the blood–brain
barrier that surrounds and protects the brain. It must therefore
be synthesized inside the brain to perform its neuronal activity.
Phenylalanine is converted into L-tyrosine by the enzyme
phenylalanine hydroxylase, with molecular oxygen (O2) and
tetrahydrobiopterin as cofactors. L-
Tyrosine is converted into L-DOPA
by the enzyme tyrosine hydroxylase, with tetrahydrobiopterin, O2, and
iron (Fe2+) as cofactors.
L-DOPA is converted into dopamine by the
enzyme aromatic L-amino acid decarboxylase (also known as DOPA
decarboxylase), with pyridoxal phosphate as the cofactor.
Dopamine itself is used as precursor in the synthesis of the
neurotransmitters norepinephrine and epinephrine.
converted into norepinephrine by the enzyme dopamine β-hydroxylase,
with O2 and L-ascorbic acid as cofactors.
converted into epinephrine by the enzyme phenylethanolamine
N-methyltransferase with S-adenosyl-L-methionine as the cofactor.
Some of the cofactors also require their own synthesis. Deficiency
in any required amino acid or cofactor can impair the synthesis of
dopamine, norepinephrine, and epinephrine.
Dopamine is broken down into inactive metabolites by a set of
enzymes—monoamine oxidase (MAO), catechol-O-methyl transferase
(COMT), and aldehyde dehydrogenase (ALDH), acting in sequence.
Both isoforms of monoamine oxidase, MAO-A and MAO-B, effectively
metabolize dopamine. Different breakdown pathways exist but the
main end-product is homovanillic acid (HVA), which has no known
biological activity. From the bloodstream, homovanillic acid is
filtered out by the kidneys and then excreted in the urine. The
two primary metabolic routes that convert dopamine into HVA are:
DOPAC → HVA – catalyzed by MAO, ALDH,
3-Methoxytyramine → HVA – catalyzed by
In clinical research on schizophrenia, measurements of homovanillic
acid in plasma have been used to estimate levels of dopamine activity
in the brain. A difficulty in this approach however, is separating the
high level of plasma homovanillic acid contributed by the metabolism
Although dopamine is normally broken down by an oxidoreductase enzyme,
it is also susceptible to oxidation by direct reaction with oxygen,
yielding quinones plus various free radicals as products. The rate
of oxidation can be increased by the presence of ferric iron or other
factors. Quinones and free radicals produced by autoxidation of
dopamine can poison cells, and there is evidence that this mechanism
may contribute to the cell loss that occurs in
Parkinson's disease and
Dopamine receptor and TAAR1
Primary targets of dopamine in the human brain
Increase intracellular levels of cAMP
by activating adenylate cyclase.
Decrease intracellular levels of cAMP
by inhibiting adenylate cyclase.
Increase intracellular levels of cAMP
and intracellular calcium concentration.
Dopamine exerts its effects by binding to and activating cell surface
receptors. In humans, dopamine has a high binding affinity at
dopamine receptors and trace amine-associated receptor 1
(TAAR1). In mammals, five subtypes of dopamine receptors have
been identified, labeled from D1 to D5. All of them function as
metabotropic, G protein-coupled receptors, meaning that they exert
their effects via a complex second messenger system. These
receptors can be divided into two families, known as D1-like and
D2-like. For receptors located on neurons in the nervous system,
the ultimate effect of D1-like activation (D1 and D5) can be
excitation (via opening of sodium channels) or inhibition (via opening
of potassium channels); the ultimate effect of D2-like activation (D2,
D3, and D4) is usually inhibition of the target neuron.
Consequently, it is incorrect to describe dopamine itself as either
excitatory or inhibitory: its effect on a target neuron depends on
which types of receptors are present on the membrane of that neuron
and on the internal responses of that neuron to the second messenger
cAMP. D1 receptors are the most numerous dopamine receptors in the
human nervous system; D2 receptors are next; D3, D4, and D5 receptors
are present at significantly lower levels.
Storage, release, and reuptake
Dopamine processing in a synapse. After release dopamine can either be
taken up again by the presynaptic terminal, or broken down by enzymes.
TH: tyrosine hydroxylase
DAT: dopamine transporter
DDC: DOPA decarboxylase
VMAT: vesicular monoamine transporter 2
COMT: Catechol-O-methyl transferase
HVA: Homovanillic acid
Inside the brain, dopamine functions as a neurotransmitter and
neuromodulator, and is controlled by a set of mechanisms common to all
monoamine neurotransmitters. After synthesis, dopamine is
transported from the cytosol into synaptic vesicles by a solute
carrier—a vesicular monoamine transporter, VMAT2.
stored in these vesicles until it is ejected into the synaptic cleft.
In most cases, the release of dopamine occurs through a process called
exocytosis which is caused by action potentials, but it can also be
caused by the activity of an intracellular trace amine-associated
TAAR1 is a high-affinity receptor for dopamine,
trace amines, and certain substituted amphetamines that is located
along membranes in the intracellular milieu of the presynaptic
cell; activation of the receptor can regulate dopamine signaling
by inducing dopamine reuptake inhibition and efflux as well as by
inhibiting neuronal firing through a diverse set of
Once in the synapse, dopamine binds to and activates dopamine
receptors. These can be postsynaptic dopamine receptors, which are
located on dendrites (the postsynaptic neuron), or presynaptic
autoreceptors (e.g., the D2sh and presynaptic D3 receptors), which are
located on the membrane of an axon terminal (the presynaptic
neuron). After the postsynaptic neuron elicits an action
potential, dopamine molecules quickly become unbound from their
receptors. They are then absorbed back into the presynaptic cell, via
reuptake mediated either by the dopamine transporter or by the plasma
membrane monoamine transporter. Once back in the cytosol, dopamine
can either be broken down by a monoamine oxidase or repackaged into
vesicles by VMAT2, making it available for future release.
In the brain the level of extracellular dopamine is modulated by two
mechanisms: phasic and tonic transmission. Phasic dopamine
release, like most neurotransmitter release in the nervous system, is
driven directly by action potentials in the dopamine-containing
cells. Tonic dopamine transmission occurs when small amounts of
dopamine are released without being preceded by presynaptic action
potentials. Tonic transmission is regulated by a variety of
factors, including the activity of other neurons and neurotransmitter
Dopaminergic cell groups and
See also: Hypothalamic–pituitary–prolactin axis
Major dopamine pathways. As part of the reward pathway, dopamine is
manufactured in nerve cell bodies located within the ventral tegmental
area (VTA) and is released in the nucleus accumbens and the prefrontal
cortex. The motor functions of dopamine are linked to a separate
pathway, with cell bodies in the substantia nigra that manufacture and
release dopamine into the dorsal striatum.
Inside the brain, dopamine plays important roles in executive
functions, motor control, motivation, arousal, reinforcement, and
reward, as well as lower-level functions including lactation, sexual
gratification, and nausea. The dopaminergic cell groups and pathways
make up the dopamine system which is neuromodulatory.
Dopaminergic neurons (dopamine-producing nerve cells) are
comparatively few in number—a total of around 400,000 in the human
brain—and their cell bodies are confined in groups to a few
relatively small brain areas. However their axons project to many
other brain areas, and they exert powerful effects on their
targets. These dopaminergic cell groups were first mapped in 1964
Annica Dahlström and Kjell Fuxe, who assigned them labels starting
with the letter "A" (for "aminergic"). In their scheme, areas A1
through A7 contain the neurotransmitter norepinephrine, whereas A8
through A14 contain dopamine. The dopaminergic areas they identified
are the substantia nigra (groups 8 and 9); the ventral tegmental area
(group 10); the posterior hypothalamus (group 11); the arcuate nucleus
(group 12); the zona incerta (group 13) and the periventricular
nucleus (group 14).
The substantia nigra is a small midbrain area that forms a component
of the basal ganglia. This has two parts—an input area called the
pars compacta and an output area the pars reticulata. The dopaminergic
neurons are found mainly in the pars compacta (cell group A8) and
nearby (group A9). In humans, the projection of dopaminergic
neurons from the substantia nigra pars compacta to the dorsal
striatum, termed the nigrostriatal pathway, plays a significant role
in the control of motor function and in learning new motor skills.
These neurons are especially vulnerable to damage, and when a large
number of them die, the result is a parkinsonian syndrome.
The ventral tegmental area (VTA) is another midbrain area. The most
prominent group of VTA dopaminergic neurons projects to the prefrontal
cortex via the mesocortical pathway and another smaller group projects
to the nucleus accumbens via the mesolimbic pathway. Together, these
two pathways are collectively termed the mesocorticolimbic
projection. The VTA also sends dopaminergic projections to the
amygdala, cingulate gyrus, hippocampus, and olfactory bulb.
Mesocorticolimbic neurons play a central role in reward and other
aspects of motivation.
The posterior hypothalamus has dopamine neurons that project to the
spinal cord, but their function is not well established. There is
some evidence that pathology in this area plays a role in restless
legs syndrome, a condition in which people have difficulty sleeping
due to an overwhelming compulsion to constantly move parts of the
body, especially the legs.
The arcuate nucleus and the periventricular nucleus of the
hypothalamus have dopamine neurons that form an important
projection—the tuberoinfundibular pathway which goes to the
pituitary gland, where it influences the secretion of the hormone
Dopamine is the primary neuroendocrine inhibitor of the
secretion of prolactin from the anterior pituitary gland. Dopamine
produced by neurons in the arcuate nucleus is secreted into the
hypophyseal portal system of the median eminence, which supplies the
pituitary gland. The prolactin cells that produce prolactin, in
the absence of dopamine, secrete prolactin continuously; dopamine
inhibits this secretion. In the context of regulating prolactin
secretion, dopamine is occasionally called prolactin-inhibiting
factor, prolactin-inhibiting hormone, or prolactostatin.
The zona incerta, grouped between the arcuate and periventricular
nuclei, projects to several areas of the hypothalamus, and
participates in the control of gonadotropin-releasing hormone, which
is necessary to activate the development of the male and female
reproductive systems, following puberty.
An additional group of dopamine-secreting neurons is found in the
retina of the eye. These neurons are amacrine cells, meaning that
they have no axons. They release dopamine into the extracellular
medium, and are specifically active during daylight hours, becoming
silent at night. This retinal dopamine acts to enhance the
activity of cone cells in the retina while suppressing rod cells—the
result is to increase sensitivity to color and contrast during bright
light conditions, at the cost of reduced sensitivity when the light is
Main circuits of the basal ganglia. The dopaminergic pathway from the
substantia nigra pars compacta to the striatum is shown in light blue.
The largest and most important sources of dopamine in the vertebrate
brain are the substantia nigra and ventral tegmental area. These
structures are closely related to each other and functionally similar
in many respects. Both are components of the basal ganglia, a
complex network of structures located mainly at the base of the
forebrain. The largest component of the basal ganglia is the
striatum. The substantia nigra sends a dopaminergic projection to
the dorsal striatum, while the ventral tegmental area sends a similar
type of dopaminergic projection to the ventral striatum.
Progress in understanding the functions of the basal ganglia has been
slow. The most popular hypotheses, broadly stated, propose that
the basal ganglia play a central role in action selection. The
action selection theory in its simplest form proposes that when a
person or animal is in a situation where several behaviors are
possible, activity in the basal ganglia determines which of them is
executed, by releasing that response from inhibition while continuing
to inhibit other motor systems that if activated would generate
competing behaviors. Thus the basal ganglia, in this concept, are
responsible for initiating behaviors, but not for determining the
details of how they are carried out. In other words, they essentially
form a decision-making system.
The basal ganglia can be divided into several sectors, and each is
involved in controlling particular types of actions. The ventral
sector of the basal ganglia (containing the ventral striatum and
ventral tegmental area) operates at the highest level of the
hierarchy, selecting actions at the whole-organism level. The
dorsal sectors (containing the dorsal striatum and substantia nigra)
operate at lower levels, selecting the specific muscles and movements
that are used to implement a given behavior pattern.
Dopamine contributes to the action selection process in at least two
important ways. First, it sets the "threshold" for initiating
actions. The higher the level of dopamine activity, the lower the
impetus required to evoke a given behavior. As a consequence, high
levels of dopamine lead to high levels of motor activity and impulsive
behavior; low levels of dopamine lead to torpor and slowed
reactions. Parkinson's disease, in which dopamine levels in the
substantia nigra circuit are greatly reduced, is characterized by
stiffness and difficulty initiating movement—however, when people
with the disease are confronted with strong stimuli such as a serious
threat, their reactions can be as vigorous as those of a healthy
person. In the opposite direction, drugs that increase dopamine
release, such as cocaine or amphetamine, can produce heightened levels
of activity, including at the extreme, psychomotor agitation and
The second important effect of dopamine is as a "teaching" signal.
When an action is followed by an increase in dopamine activity, the
basal ganglia circuit is altered in a way that makes the same response
easier to evoke when similar situations arise in the future. This
is a form of operant conditioning, in which dopamine plays the role of
a reward signal.
Illustration of dopaminergic reward structures
In the reward system, reward is the attractive and motivational
property of a stimulus that induces appetitive behavior (also known as
approach behavior) – and consummatory behavior. A rewarding
stimulus is one that has the potential to cause an approach to it and
a choice to be made to consume it or not. Pleasure, learning
(e.g., classical and operant conditioning), and approach behavior are
the three main functions of reward. As an aspect of reward,
pleasure provides a definition of reward; however, while all
pleasurable stimuli are rewarding, not all rewarding stimuli are
pleasurable (e.g., extrinstic rewards like money). The
motivational or desirable aspect of rewarding stimuli is reflected by
the approach behavior that they induce, whereas the pleasurable
component of intrinstic rewards is derived from the consummatory
behavior that ensues upon acquiring them. A neuropsychological
model which distinguishes these two components of an intrinsically
rewarding stimulus is the incentive salience model, where "wanting" or
desire (less commonly, "seeking") corresponds to appetitive or
approach behavior while "liking" or pleasure corresponds to
consummatory behavior. In human drug addicts, "wanting"
becomes dissociated with "liking" as the desire to use an addictive
drug increases, while the pleasure obtained from consuming it
decreases due to drug tolerance.
Within the brain, dopamine functions partly as a "global reward
signal", where an initial phasic dopamine response to a rewarding
stimulus encodes information about the salience, value, and context of
a reward. In the context of reward-related learning, dopamine also
functions as a reward prediction error signal, that is, the degree to
which the value of a reward is unexpected. According to this
hypothesis of Wolfram Schultz, rewards that are expected do not
produce a second phasic dopamine response in certain dopaminergic
cells, but rewards that are unexpected, or greater than expected,
produce a short-lasting increase in synaptic dopamine, whereas the
omission of an expected reward actually causes dopamine release to
drop below its background level. The "prediction error" hypothesis
has drawn particular interest from computational neuroscientists,
because an influential computational-learning method known as temporal
difference learning makes heavy use of a signal that encodes
prediction error. This confluence of theory and data has led to a
fertile interaction between neuroscientists and computer scientists
interested in machine learning.
Evidence from microelectrode recordings from the brains of animals
shows that dopamine neurons in the ventral tegmental area (VTA) and
substantia nigra are strongly activated by a wide variety of rewarding
events. These reward-responsive dopamine neurons in the VTA and
substantia nigra are crucial for reward-related cognition and serve as
the central component of the reward system. The function
of dopamine varies in each axonal projection from the VTA and
substantia nigra; for example, the VTA–nucleus accumbens shell
projection assigns incentive salience ("want") to rewarding stimuli
and its associated cues, the VTA–orbitofrontal cortex projection
updates the value of different goals in accordance with their
incentive salience, the VTA–amygdala and VTA–hippocampus
projections mediate the consolidation of reward-related memories, and
both the VTA–nucleus accumbens core and substantia nigra–dorsal
striatum pathways are involved in learning motor responses that
facilitate the acquisition of rewarding stimuli. Some activity
within the VTA dopaminergic projections appears to be associated with
reward prediction as well.
While dopamine has a central role in mediating "wanting" —
associated with the appetitive or approach behavioral responses to
rewarding stimuli, detailed studies have shown that dopamine cannot
simply be equated with hedonic "liking" or pleasure, as reflected in
the consummatory behavioral response.
is involved in some but not all aspects of pleasure-related cognition,
since pleasure centers have been identified both within the dopamine
system (i.e., nucleus accumbens shell) and outside the dopamine system
(i.e., ventral pallidum and parabrachial nucleus). For
example, direct electrical stimulation of dopamine pathways, using
electrodes implanted in the brain, is experienced as pleasurable, and
many types of animals are willing to work to obtain it.
Antipsychotic drugs used to treat psychosis reduce dopamine levels and
tend to cause anhedonia, a diminished ability to experience
pleasure. Many types of pleasurable experiences—such as sex,
enjoying food, or playing video games—increase dopamine release.
All addictive drugs directly or indirectly affect dopamine
neurotransmission in the nucleus accumbens; these drugs
increase drug "wanting", leading to compulsive drug use, when
repeatedly taken in high doses, presumably through the sensitization
of incentive-salience. Drugs that increase synaptic dopamine
concentrations include psychostimulants such as methamphetamine and
cocaine. These produce increases in "wanting" behaviors, but do not
greatly alter expressions of pleasure or change levels of
satiation. However, opiate drugs such as heroin or morphine
produce increases in expressions of "liking" and "wanting"
behaviors. Moreover, animals in which the ventral tegmental
dopamine system has been rendered inactive do not seek food, and will
starve to death if left to themselves, but if food is placed in their
mouths they will consume it and show expressions indicative of
Outside the nervous system
Dopamine does not cross the blood–brain barrier, so its synthesis
and functions in peripheral areas are to a large degree independent of
its synthesis and functions in the brain. A substantial amount of
dopamine circulates in the bloodstream, but its functions there are
not entirely clear.
Dopamine is found in blood plasma at levels
comparable to those of epinephrine, but in humans, over 95% of the
dopamine in the plasma is in the form of dopamine sulfate, a conjugate
produced by the enzyme sulfotransferase 1A3/1A4 acting on free
dopamine. The bulk of this dopamine sulfate is produced in the
mesentery that surrounds parts of the digestive system. The
production of dopamine sulfate is thought to be a mechanism for
detoxifying dopamine that is ingested as food or produced by the
digestive process—levels in the plasma typically rise more than
fifty-fold after a meal.
Dopamine sulfate has no known biological
functions and is excreted in urine.
The relatively small quantity of unconjugated dopamine in the
bloodstream may be produced by the sympathetic nervous system, the
digestive system, or possibly other organs. It may act on dopamine
receptors in peripheral tissues, or be metabolized, or be converted to
norepinephrine by the enzyme dopamine beta hydroxylase, which is
released into the bloodstream by the adrenal medulla. Some
dopamine receptors are located in the walls of arteries, where they
act as a vasodilator and an inhibitor of norepinephrine release.
These responses might be activated by dopamine released from the
carotid body under conditions of low oxygen, but whether arterial
dopamine receptors perform other biologically useful functions is not
Beyond its role in modulating blood flow, there are several peripheral
systems in which dopamine circulates within a limited area and
performs an exocrine or paracrine function. The peripheral systems
in which dopamine plays an important role include the immune system,
the kidneys and the pancreas.
In the immune system dopamine acts upon receptors present on immune
cells, especially lymphocytes.
Dopamine can also affect immune
cells in the spleen, bone marrow, and circulatory system. In
addition, dopamine can be synthesized and released by immune cells
themselves. The main effect of dopamine on lymphocytes is to
reduce their activation level. The functional significance of this
system is unclear, but it affords a possible route for interactions
between the nervous system and immune system, and may be relevant to
some autoimmune disorders.
The renal dopaminergic system is located in the cells of the nephron
in the kidney, where all subtypes of dopamine receptors are
Dopamine is also synthesized there, by tubule cells, and
discharged into the tubular fluid. Its actions include increasing the
blood supply to the kidneys, increasing the glomerular filtration
rate, and increasing the excretion of sodium in the urine. Hence,
defects in renal dopamine function can lead to reduced sodium
excretion and consequently result in the development of high blood
pressure. There is strong evidence that faults in the production of
dopamine or in the receptors can result in a number of pathologies
including oxidative stress, edema, and either genetic or essential
Oxidative stress can itself cause hypertension.
Defects in the system can also be caused by genetic factors or high
In the pancreas the role of dopamine is somewhat complex. The pancreas
consists of two parts, an exocrine and an endocrine component. The
exocrine part synthesizes and secretes digestive enzymes and other
substances, including dopamine, into the small intestine. The
function of this secreted dopamine after it enters the small intestine
is not clearly established—the possibilities include protecting the
intestinal mucosa from damage and reducing gastrointestinal motility
(the rate at which content moves through the digestive system).
The pancreatic islets make up the endocrine part of the pancreas, and
synthesize and secrete hormones including insulin into the
bloodstream. There is evidence that the beta cells in the islets
that synthesize insulin contain dopamine receptors, and that dopamine
acts to reduce the amount of insulin they release. The source of
their dopamine input is not clearly established—it may come from
dopamine that circulates in the bloodstream and derives from the
sympathetic nervous system, or it may be synthesized locally by other
types of pancreatic cells.
Dopamine HCl preparation, single dose vial for intravenous
Dopamine as a manufactured medication is sold under the trade names
Intropin, Dopastat, and Revimine, among others. It is on the World
Health Organization's List of Essential Medicines. It is most
commonly used as a stimulant drug in the treatment of severe low blood
pressure, slow heart rate, and cardiac arrest. It is especially
important in treating these in newborn infants. It is given
intravenously. Since the half-life of dopamine in plasma is very
short—approximately one minute in adults, two minutes in newborn
infants and up to five minutes in preterm infants—it is usually
given in a continuous intravenous drip rather than a single
Its effects, depending on dosage, include an increase in sodium
excretion by the kidneys, an increase in urine output, an increase in
heart rate, and an increase in blood pressure. At low doses it
acts through the sympathetic nervous system to increase heart muscle
contraction force and heart rate, thereby increasing cardiac output
and blood pressure. Higher doses also cause vasoconstriction that
further increases blood pressure. Older literature also
describes very low doses thought to improve kidney function without
other consequences, but recent reviews have concluded that doses at
such low levels are not effective and may sometimes be harmful.
While some effects result from stimulation of dopamine receptors, the
prominent cardiovascular effects result from dopamine acting at α1,
β1, and β2 adrenergic receptors.
Side effects of dopamine include negative effects on kidney function
and irregular heartbeats. The LD50, or lethal dose which is
expected to prove fatal in 50% of the population, has been found to
be: 59 mg/kg (mouse; administered intravenously); 95 mg/kg
(mouse; administered intraperitoneally); 163 mg/kg (rat;
administered intraperitoneally); 79 mg/kg (dog; administered
A fluorinated form of
L-DOPA known as fluorodopa is available for use
in positron emission tomography to assess the function of the
Disease, disorders, and pharmacology
See also: List of dopaminergic drugs
The dopamine system plays a central role in several significant
medical conditions, including Parkinson's disease, attention deficit
hyperactivity disorder, schizophrenia, bipolar disorder, and
addiction. Aside from dopamine itself, there are many other important
drugs that act on dopamine systems in various parts of the brain or
body. Some are used for medical or recreational purposes, but
neurochemists have also developed a variety of research drugs, some of
which bind with high affinity to specific types of dopamine receptors
and either agonize or antagonize their effects, and many that affect
other aspects of dopamine physiology, including dopamine
transporter inhibitors, VMAT inhibitors, and enzyme inhibitors.
Main article: Aging brain
A number of studies have reported an age-related decline in dopamine
synthesis and dopamine receptor density (i.e., the number of
receptors) in the brain. This decline has been shown to occur in
the striatum and extrastriatal regions. Decreases in the D1, D2,
and D3 receptors are well documented. The reduction of
dopamine with aging is thought to be responsible for many neurological
symptoms that increase in frequency with age, such as decreased arm
swing and increased rigidity. Changes in dopamine levels may also
cause age-related changes in cognitive flexibility.
Other neurotransmitters, such as serotonin and glutamate also show a
decline in output with aging.
Parkinson's disease is an age-related disorder characterized by
movement disorders such as stiffness of the body, slowing of movement,
and trembling of limbs when they are not in use. In advanced
stages it progresses to dementia and eventually death. The main
symptoms are caused by the loss of dopamine-secreting cells in the
substantia nigra. These dopamine cells are especially vulnerable
to damage, and a variety of insults, including encephalitis (as
depicted in the book and movie "Awakenings"), repeated sports-related
concussions, and some forms of chemical poisoning such as MPTP, can
lead to substantial cell loss, producing a parkinsonian syndrome that
is similar in its main features to Parkinson's disease. Most cases
of Parkinson's disease, however, are idiopathic, meaning that the
cause of cell death cannot be identified.
The most widely used treatment for parkinsonism is administration of
L-DOPA, the metabolic precursor for dopamine.
L-DOPA is converted
to dopamine in the brain and various parts of the body by the enzyme
L-DOPA is used rather than dopamine itself
because, unlike dopamine, it is capable of crossing the blood-brain
barrier. It is often co-administered with an enzyme inhibitor of
peripheral decarboxylation such as carbidopa or benserazide, to reduce
the amount converted to dopamine in the periphery and thereby increase
the amount of
L-DOPA that enters the brain. When
administered regularly over a long time period, a variety of
unpleasant side effects such as dyskinesia often begin to appear; even
so, it is considered the best available long-term treatment option for
most cases of Parkinson's disease.
L-DOPA treatment cannot restore the dopamine cells that have been
lost, but it causes the remaining cells to produce more dopamine,
thereby compensating for the loss to at least some degree. In
advanced stages the treatment begins to fail because the cell loss is
so severe that the remaining ones cannot produce enough dopamine
L-DOPA levels. Other drugs that enhance dopamine
function, such as bromocriptine and pergolide, are also sometimes used
to treat Parkinsonism, but in most cases
L-DOPA appears to give the
best trade-off between positive effects and negative side-effects.
Dopaminergic medications that are used to treat Parkinson's disease
are sometimes associated with the development of a dopamine
dysregulation syndrome, which involves the overuse of dopaminergic
medication and medication-induced compulsive engagement in natural
rewards like gambling and sexual activity. The latter
behaviors are similar to those observed in individuals with a
Drug addiction and psychostimulants
Main article: Addiction
Cocaine increases dopamine levels by blocking dopamine transporters
(DAT), which transport dopamine back into a synaptic terminal after it
has been emitted.
Cocaine, substituted amphetamines (including methamphetamine),
Adderall, methylphenidate (marketed as Ritalin or Concerta), MDMA
(ecstasy) and other psychostimulants exert their effects primarily or
partly by increasing dopamine levels in the brain by a variety of
Cocaine and methylphenidate are dopamine transporter
blockers or reuptake inhibitors; they non-competitively inhibit
dopamine reuptake, resulting in increased dopamine concentrations in
the synaptic cleft.:54–58 Like cocaine, substituted
amphetamines and amphetamine also increase the concentration of
dopamine in the synaptic cleft, but by different
The effects of psychostimulants include increases in heart rate, body
temperature, and sweating; improvements in alertness, attention, and
endurance; increases in pleasure produced by rewarding events; but at
higher doses agitation, anxiety, or even loss of contact with
reality. Drugs in this group can have a high addiction potential,
due to their activating effects on the dopamine-mediated reward system
in the brain. However some can also be useful, at lower doses, for
treating attention deficit hyperactivity disorder (ADHD) and
narcolepsy. An important differentiating factor is the onset
and duration of action.
Cocaine can take effect in seconds if it
is injected or inhaled in free base form; the effects last from 5 to
90 minutes. This rapid and brief action makes its effects easily
perceived and consequently gives it high addiction potential.
Methylphenidate taken in pill form, in contrast, can take two hours to
reach peak levels in the bloodstream, and depending on formulation
the effects can last for up to 12 hours. These
slow and sustained actions reduce the potential for abuse and make it
more useful for treating ADHD.[not in citation given]
Methamphetamine hydrochloride also known as crystal meth
A variety of addictive drugs produce an increase in reward-related
dopamine activity. Stimulants such as nicotine, cocaine and
methamphetamine promote increased levels of dopamine which appear to
be the primary factor in causing addiction. For other addictive drugs
such as the opioid heroin, the increased levels of dopamine in the
reward system may only play a minor role in addiction. When people
addicted to stimulants go through withdrawal, they do not experience
the physical suffering associated with alcohol withdrawal or
withdrawal from opiates; instead they experience craving, an intense
desire for the drug characterized by irritability, restlessness, and
other arousal symptoms, brought about by psychological dependence.
The dopamine system plays a crucial role in several aspects of
addiction. At the earliest stage, genetic differences that alter the
expression of dopamine receptors in the brain can predict whether a
person will find stimulants appealing or aversive. Consumption of
stimulants produces increases in brain dopamine levels that last from
minutes to hours. Finally, the chronic elevation in dopamine that
comes with repetitive high-dose stimulant consumption triggers a
wide-ranging set of structural changes in the brain that are
responsible for the behavioral abnormalities which characterize an
addiction. Treatment of stimulant addiction is very difficult,
because even if consumption ceases, the craving that comes with
psychological withdrawal does not. Even when the craving seems to
be extinct, it may re-emerge when faced with stimuli that are
associated with the drug, such as friends, locations and
situations. Association networks in the brain are greatly
Psychosis and antipsychotic drugs
Main article: Psychosis
Psychiatrists in the early 1950s discovered that a class of drugs
known as typical antipsychotics (also known as major tranquilizers),
were often effective at reducing the psychotic symptoms of
schizophrenia. The introduction of the first widely used
antipsychotic, chlorpromazine (Thorazine), in the 1950s, led to the
release of many patients with schizophrenia from institutions in the
years that followed. By the 1970s researchers understood that
these typical antipsychotics worked as antagonists on the D2
receptors. This realization led to the so-called dopamine
hypothesis of schizophrenia, which postulates that schizophrenia is
largely caused by hyperactivity of brain dopamine systems. The
dopamine hypothesis drew additional support from the observation that
psychotic symptoms were often intensified by dopamine-enhancing
stimulants such as methamphetamine, and that these drugs could also
produce psychosis in healthy people if taken in large enough
doses. In the following decades other atypical antipsychotics that
had fewer serious side effects were developed. Many of these newer
drugs do not act directly on dopamine receptors, but instead produce
alterations in dopamine activity indirectly. These drugs were
also used to treat other psychoses.
Antipsychotic drugs have a
broadly suppressive effect on most types of active behavior, and
particularly reduce the delusional and agitated behavior
characteristic of overt psychosis. There remains substantial
dispute, however, about how much of an improvement the patient
experiences on these drugs.
Later observations, however, have caused the dopamine hypothesis to
lose popularity, at least in its simple original form. For one
thing, patients with schizophrenia do not typically show measurably
increased levels of brain dopamine activity. Also, other
dissociative drugs, notably ketamine and phencyclidine that act on
glutamate NMDA receptors (and not on dopamine receptors) can produce
psychotic symptoms. Perhaps most importantly, those drugs that do
reduce dopamine activity are a very imperfect treatment for
schizophrenia: they only reduce a subset of symptoms, while producing
severe short-term and long-term side effects. Even so, many
psychiatrists and neuroscientists continue to believe that
schizophrenia involves some sort of dopamine system dysfunction.
As the "dopamine hypothesis" has evolved over time, however, the sorts
of dysfunctions it postulates have tended to become increasingly
subtle and complex.
However, the widespread use of antipsychotic drugs has long been
controversial. There are several reasons for this. First,
antipsychotic drugs are perceived as very aversive by people who have
to take them, because they produce a general dullness of thought and
suppress the ability to experience pleasure. Second, it is
difficult to show that they act specifically against psychotic
behaviors rather than merely suppressing all types of active
behavior. Third, they can produce a range of serious side
effects, including weight gain, diabetes, fatigue, sexual dysfunction,
hormonal changes, and a type of serious movement disorder known as
tardive dyskinesia. Some of these side effects may continue long
after the cessation of drug use, or even permanently.
Attention deficit hyperactivity disorder
Altered dopamine neurotransmission is implicated in attention deficit
hyperactivity disorder (ADHD), a condition associated with impaired
cognitive control, in turn leading to problems with regulating
attention (attentional control), inhibiting behaviors (inhibitory
control), and forgetting things or missing details (working memory),
among other problems. There are genetic links between dopamine
receptors, the dopamine transporter, and ADHD, in addition to links to
other neurotransmitter receptors and transporters. The most
important relationship between dopamine and ADHD involves the drugs
that are used to treat ADHD. Some of the most effective
therapeutic agents for ADHD are psychostimulants such as
methylphenidate (Ritalin, Concerta) and amphetamine (Adderall,
Dexedrine), drugs that increase both dopamine and norepinephrine
levels in the brain. The clinical effects of these
psychostimulants in treating ADHD are mediated through the indirect
activation of dopamine and norepinephrine receptors, specifically
dopamine receptor D1 and adrenoceptor A2, in the prefrontal
Dopamine plays a role in pain processing in multiple levels of the
central nervous system including the spinal cord, periaqueductal gray,
thalamus, basal ganglia, and cingulate cortex. Decreased levels
of dopamine have been associated with painful symptoms that frequently
occur in Parkinson's disease. Abnormalities in dopaminergic
neurotransmission also occur in several painful clinical conditions,
including burning mouth syndrome, fibromyalgia, and restless legs
Nausea and vomiting are largely determined by activity in the area
postrema in the medulla of the brainstem, in a region known as the
chemoreceptor trigger zone. This area contains a large population
of type D2 dopamine receptors. Consequently, drugs that activate
D2 receptors have a high potential to cause nausea. This group
includes some medications that are administered for Parkinson's
disease, as well as other dopamine agonists such as apomorphine.
In some cases, D2-receptor antagonists such as metoclopramide are
useful as anti-nausea drugs.
Comparative biology and evolution
There are no reports of dopamine in archaea, but it has been detected
in some types of bacteria and in the protozoan called
Tetrahymena. Perhaps more importantly, there are types of
bacteria that contain homologs of all the enzymes that animals use to
synthesize dopamine. It has been proposed that animals derived
their dopamine-synthesizing machinery from bacteria, via horizontal
gene transfer that may have occurred relatively late in evolutionary
time, perhaps as a result of the symbiotic incorporation of bacteria
into eukaryotic cells that gave rise to mitochondria.
Dopamine is used as a neurotransmitter in most multicellular
animals. In sponges there is only a single report of the presence
of dopamine, with no indication of its function; however,
dopamine has been reported in the nervous systems of many other
radially symmetric species, including the cnidarian jellyfish, hydra
and some corals. This dates the emergence of dopamine as a
neurotransmitter back to the earliest appearance of the nervous
system, over 500 million years ago in the
Cambrian era. Dopamine
functions as a neurotransmitter in vertebrates, echinoderms,
arthropods, molluscs, and several types of worm.
In every type of animal that has been examined, dopamine has been seen
to modify motor behavior. In the model organism, nematode
Caenorhabditis elegans, it reduces locomotion and increases
food-exploratory movements; in flatworms it produces "screw-like"
movements; in leeches it inhibits swimming and promotes crawling.
Across a wide range of vertebrates, dopamine has an "activating"
effect on behavior-switching and response selection, comparable to its
effect in mammals.
Dopamine has also consistently been shown to play a role in reward
learning, in all animal groups. As in all vertebrates –
invertebrates such as roundworms, flatworms, molluscs and common fruit
flies can all be trained to repeat an action if it is consistently
followed by an increase in dopamine levels.
It had long been believed that arthropods were an exception to this
with dopamine being seen as having an adverse effect. Reward was seen
to be mediated instead by octopamine, a neurotransmitter closely
related to norepinephrine. More recent studies however have shown
that dopamine does play a part in reward learning in fruit flies. Also
it has been found that the rewarding effect of octopamine is due to
its activating a set of dopaminergic neurons not previously accessed
in the research.
Dopamine can be found in the peel and fruit pulp of bananas.
Many plants, including a variety of food plants, synthesize dopamine
to varying degrees. The highest concentrations have been observed
in bananas—the fruit pulp of red and yellow bananas contains
dopamine at levels of 40 to 50 parts per million by weight.
Potatoes, avocados, broccoli, and Brussels sprouts may also contain
dopamine at levels of 1 part per million or more; oranges, tomatoes,
spinach, beans, and other plants contain measurable concentrations
less than 1 part per million. The dopamine in plants is
synthesized from the amino acid tyrosine, by biochemical mechanisms
similar to those that animals use. It can be metabolized in a
variety of ways, producing melanin and a variety of alkaloids as
byproducts. The functions of plant catecholamines have not been
clearly established, but there is evidence that they play a role in
the response to stressors such as bacterial infection, act as
growth-promoting factors in some situations, and modify the way that
sugars are metabolized. The receptors that mediate these actions have
not yet been identified, nor have the intracellular mechanisms that
Dopamine consumed in food cannot act on the brain, because it cannot
cross the blood–brain barrier. However, there are also a variety
of plants that contain L-DOPA, the metabolic precursor of
dopamine. The highest concentrations are found in the leaves and
bean pods of plants of the genus Mucuna, especially in
(velvet beans), which have been used as a source for
L-DOPA as a
drug. Another plant containing substantial amounts of
Vicia faba, the plant that produces fava beans (also known as "broad
beans"). The level of
L-DOPA in the beans, however, is much lower than
in the pod shells and other parts of the plant. The seeds of
Bauhinia trees also contain substantial amounts of
In a species of marine green algae Ulvaria obscura, a major component
of some algal blooms, dopamine is present in very high concentrations,
estimated at 4.4% of dry weight. There is evidence that this dopamine
functions as an anti-herbivore defense, reducing consumption by snails
As a precursor for melanin
Melanins are a family of dark-pigmented substances found in a wide
range of organisms. Chemically they are closely related to
dopamine, and there is a type of melanin, known as dopamine-melanin,
that can be synthesized by oxidation of dopamine via the enzyme
tyrosinase. The melanin that darkens human skin is not of this
type: it is synthesized by a pathway that uses
L-DOPA as a precursor
but not dopamine. However, there is substantial evidence that the
neuromelanin that gives a dark color to the brain's substantia nigra
is at least in part dopamine-melanin.
Dopamine-derived melanin probably appears in at least some other
biological systems as well. Some of the dopamine in plants is likely
to be used as a precursor for dopamine-melanin. The complex
patterns that appear on butterfly wings, as well as black-and-white
stripes on the bodies of insect larvae, are also thought to be caused
by spatially structured accumulations of dopamine-melanin.
History and development
Main article: History of catecholamine research
Dopamine was first synthesized in 1910 by
George Barger and James
Ewens at Wellcome Laboratories in London, England and first
identified in the human brain by
Kathleen Montagu in 1957. It was
named dopamine because it is a monoamine whose precursor in the
Barger-Ewens synthesis is 3,4-dihydroxyphenylalanine (levodopa or
L-DOPA). Dopamine's function as a neurotransmitter was first
recognized in 1958 by
Arvid Carlsson and
Nils-Åke Hillarp at the
Laboratory for Chemical Pharmacology of the National Heart Institute
of Sweden. Carlsson was awarded the 2000 Nobel Prize in
Physiology or Medicine for showing that dopamine is not only a
precursor of norepinephrine (noradrenaline) and epinephrine
(adrenaline), but is also itself a neurotransmitter.
Research motivated by adhesive polyphenolic proteins in mussels led to
the discovery in 2007 that a wide variety of materials, if placed in a
solution of dopamine at slightly basic pH, will become coated with a
layer of polymerized dopamine, often referred to as
polydopamine. This polymerized dopamine forms by a
spontaneous oxidation reaction, and is formally a type of
melanin. Synthesis usually involves reaction of dopamine
Tris as a base in water. The structure of
polydopamine is unknown.
Polydopamine coatings can form on objects ranging in size from
nanoparticles to large surfaces. Polydopamine layers have
chemical properties that have the potential to be extremely useful,
and numerous studies have examined their possible applications.
At the simplest level, they can be used for protection against damage
by light, or to form capsules for drug delivery. At a more
sophisticated level, their adhesive properties may make them useful as
substrates for biosensors or other biologically active
^ a b c d "Dopamine: Biological activity". IUPHAR/BPS guide to
pharmacology. International Union of Basic and Clinical Pharmacology.
Retrieved 29 January 2016.
^ "Dissecting components of reward: 'liking', 'wanting', and
learning". 9 (1). Curr Opin Pharmacol. 2009: 65–73.
PMC 2756052 .
^ "What is the role of dopamine in reward: hedonic impact, reward
learning, or incentive salience?".
Brain Res Rev. 28 (3):
309–69. 1998. PMID 9858756.
^ Moncrieff J (2008). The myth of the chemical cure. A critique of
psychiatric drug treatment. Basingstoke, UK: Palgrave MacMillan.
^ Volkow ND, Wang GJ, Kollins SH, Wigal TL, Newcorn JH, Telang F,
Fowler JS, Zhu W, Logan J, Ma Y, Pradhan K, Wong C, Swanson JM
(September 2009). "Evaluating dopamine reward pathway in ADHD:
clinical implications". JAMA. 302 (10): 1084–91.
doi:10.1001/jama.2009.1308. PMC 2958516 .
^ "Dopamine". PubChem. Retrieved 21 September 2015.
^ "Catecholamine". Brittanica. Retrieved 21 September 2015.
^ "Phenylethylamine". ChemicalLand21.com. Retrieved 21 September
^ a b c d e f g Carter JE, Johnson JH, Baaske DM (1982). "Dopamine
Hydrochloride". Analytical Profiles of Drug Substances. 11:
^ a b c Broadley KJ (March 2010). "The vascular effects of trace
amines and amphetamines". Pharmacol. Ther. 125 (3): 363–375.
doi:10.1016/j.pharmthera.2009.11.005. PMID 19948186.
^ a b c Lindemann L, Hoener MC (May 2005). "A renaissance in trace
amines inspired by a novel GPCR family". Trends Pharmacol. Sci. 26
(5): 274–281. doi:10.1016/j.tips.2005.03.007.
^ a b c d Wang X, Li J, Dong G, Yue J (February 2014). "The endogenous
substrates of brain CYP2D". Eur. J. Pharmacol. 724: 211–218.
doi:10.1016/j.ejphar.2013.12.025. PMID 24374199.
^ a b c d e f Seeman P (2009). "Chapter 1: Historical overview:
Introduction to the dopamine receptors". In Neve K. The Dopamine
Receptors. Springer. pp. 1–22.
^ "EC 22.214.171.124 –
Tyrosine 3-monooxygenase (Homo sapiens)".
BRENDA. Technische Universität Braunschweig. July 2016. Retrieved 7
October 2016. Substrate: L-phenylalanine + tetrahydrobiopterin + O2
Product: L-tyrosine + 3-hydroxyphenylalanine [(aka m-tyrosine)] +
dihydropteridine + H2O
Organism: Homo sapiens
^ "EC 126.96.36.199 – Aromatic-L-amino-acid decarboxylase (Homo
sapiens)". BRENDA. Technische Universität Braunschweig. July 2016.
Retrieved 7 October 2016. Substrate: m-tyrosine
Product: m-tyramine + CO2
Organism: Homo sapiens
^ a b c d e f g h i j Musacchio JM (2013). "Chapter 1: Enzymes
involved in the biosynthesis and degradation of catecholamines". In
Iverson L. Biochemistry of Biogenic Amines. Springer. pp. 1–35.
^ a b c d e f g h i j k The National Collaborating Centre for Chronic
Conditions, ed. (2006). "Symptomatic pharmacological therapy in
Parkinson's disease". Parkinson's Disease. London: Royal College of
Physicians. pp. 59–100. ISBN 978-1-86016-283-1. Retrieved
24 September 2015.
^ a b c d e f g h i j k Eisenhofer G, Kopin IJ, Goldstein DS
(September 2004). "
Catecholamine metabolism: a contemporary view with
implications for physiology and medicine". Pharmacological Reviews. 56
(3): 331–49. doi:10.1124/pr.56.3.1. PMID 15317907.
^ Amin F, Davidson M, Davis KL (1992). "
Homovanillic acid measurement
in clinical research: a review of methodology". Schizophrenia
Bulletin. 18 (1): 123–48. doi:10.1093/schbul/18.1.123.
^ Amin F, Davidson M, Kahn RS, Schmeidler J, Stern R, Knott PJ, Apter
S (1995). "Assessment of the central dopaminergic index of plasma HVA
Schizophrenia Bulletin. 21 (1): 53–66.
doi:10.1093/schbul/21.1.53. PMID 7770741.
^ Sulzer D, Zecca L (February 2000). "Intraneuronal dopamine-quinone
synthesis: a review".
Neurotoxicity Research. 1 (3): 181–95.
doi:10.1007/BF03033289. PMID 12835101.
^ Miyazaki I, Asanuma M (June 2008). "
oxidative stress caused by dopamine itself" (PDF). Acta Medica
Okayama. 62 (3): 141–50. doi:10.18926/AMO/30942.
^ a b c d e Grandy DK, Miller GM, Li JX (February 2016). ""TAARgeting
Addiction"--The Alamo Bears Witness to Another Revolution: An Overview
of the Plenary Symposium of the 2015 Behavior, Biology and Chemistry
Conference". Drug and Alcohol Dependence. 159: 9–16.
doi:10.1016/j.drugalcdep.2015.11.014. PMC 4724540 .
TAAR1 is a high-affinity receptor for METH/AMPH
^ a b c d Romanelli RJ, Williams JT, Neve KA (2009). "Chapter 6:
Dopamine receptor signalling: intracellular pathways to behavior". In
Neve KA. The
Dopamine Receptors. Springer. pp. 137–174.
^ a b Eiden LE, Schäfer MK, Weihe E, Schütz B (February 2004). "The
vesicular amine transporter family (SLC18): amine/proton antiporters
required for vesicular accumulation and regulated exocytotic secretion
of monoamines and acetylcholine". Pflügers Archiv. 447 (5): 636–40.
doi:10.1007/s00424-003-1100-5. PMID 12827358.
^ a b Miller GM (January 2011). "The emerging role of trace
amine-associated receptor 1 in the functional regulation of monoamine
transporters and dopaminergic activity". Journal of Neurochemistry.
116 (2): 164–76. doi:10.1111/j.1471-4159.2010.07109.x.
PMC 3005101 . PMID 21073468.
^ a b Beaulieu JM, Gainetdinov RR (March 2011). "The physiology,
signaling, and pharmacology of dopamine receptors". Pharmacological
Reviews. 63 (1): 182–217. doi:10.1124/pr.110.002642.
^ Torres GE, Gainetdinov RR, Caron MG (January 2003). "Plasma membrane
monoamine transporters: structure, regulation and function". Nature
Reviews. Neuroscience. 4 (1): 13–25. doi:10.1038/nrn1008.
^ a b c d Rice ME, Patel JC, Cragg SJ (December 2011). "Dopamine
release in the basal ganglia". Neuroscience. 198: 112–37.
doi:10.1016/j.neuroscience.2011.08.066. PMC 3357127 .
^ Schultz W (2007). "Multiple dopamine functions at different time
courses". Annual Review of Neuroscience. 30: 259–88.
doi:10.1146/annurev.neuro.28.061604.135722. PMID 17600522.
^ a b c d e f g h i Björklund A, Dunnett SB (May 2007). "Dopamine
neuron systems in the brain: an update". Trends in Neurosciences. 30
(5): 194–202. doi:10.1016/j.tins.2007.03.006.
^ a b Dahlstroem A, Fuxe K (1964). "Evidence for the existence of
monoamine-containing neurons in the central nervous system. I.
Demonstration of monoamines in the cell bodies of brain stem neurons".
Acta Physiologica Scandinavica. Supplementum. 232: SUPPL 232:1–55.
^ a b c d Malenka RC, Nestler EJ, Hyman SE (2009). "Chapter 6: Widely
Projecting Systems: Monoamines, Acetylcholine, and Orexin". In Sydor
A, Brown RY. Molecular Neuropharmacology: A Foundation for Clinical
Neuroscience (2nd ed.). New York: McGraw-Hill Medical.
pp. 147–148, 154–157. ISBN 978-0-07-148127-4.
^ Christine CW, Aminoff MJ (September 2004). "Clinical differentiation
of parkinsonian syndromes: prognostic and therapeutic relevance". The
American Journal of Medicine. 117 (6): 412–9.
doi:10.1016/j.amjmed.2004.03.032. PMID 15380498.
^ a b Paulus W, Schomburg ED (June 2006). "
Dopamine and the spinal
cord in restless legs syndrome: does spinal cord physiology reveal a
basis for augmentation?". Sleep Medicine Reviews. 10 (3): 185–96.
doi:10.1016/j.smrv.2006.01.004. PMID 16762808.
^ a b c d e f Ben-Jonathan N, Hnasko R (December 2001). "
Dopamine as a
prolactin (PRL) inhibitor". Endocrine Reviews. 22 (6): 724–63.
doi:10.1210/er.22.6.724. PMID 11739329.
^ a b c d Witkovsky P (January 2004). "
Dopamine and retinal function".
Documenta Ophthalmologica. Advances in Ophthalmology. 108 (1):
^ a b Fix JD (2008). "Basal Ganglia and the Striatal Motor System".
Neuroanatomy (Board Review Series) (4th ed.). Baltimore: Wulters
Kluwer & Lippincott Wiliams & Wilkins. pp. 274–281.
^ a b c d e f Chakravarthy VS, Joseph D, Bapi RS (September 2010).
"What do the basal ganglia do? A modeling perspective" (PDF).
Biological Cybernetics. 103 (3): 237–53.
doi:10.1007/s00422-010-0401-y. PMID 20644953.
^ a b c d Floresco SB (January 2015). "The nucleus accumbens: an
interface between cognition, emotion, and action" (PDF). Annual Review
of Psychology. 66: 25–52. doi:10.1146/annurev-psych-010213-115159.
^ a b Balleine BW, Dezfouli A, Ito M, Doya K (2015). "Hierarchical
control of goal-directed action in the cortical–basal ganglia
network". Current Opinion in Behavioral Sciences. 5: 1–7.
^ a b c Jankovic J (April 2008). "Parkinson's disease: clinical
features and diagnosis". Journal of Neurology, Neurosurgery, and
Psychiatry. 79 (4): 368–76. doi:10.1136/jnnp.2007.131045.
^ Pattij T, Vanderschuren LJ (April 2008). "The neuropharmacology of
impulsive behaviour" (PDF). Trends in Pharmacological Sciences. 29
(4): 192–9. doi:10.1016/j.tips.2008.01.002.
^ a b c d e f g h i j k l m Schultz W (July 2015). "Neuronal Reward
and Decision Signals: From Theories to Data".
95 (3): 853–951. doi:10.1152/physrev.00023.2014.
PMC 4491543 . PMID 26109341.
^ a b c Robinson TE, Berridge KC (1993). "The neural basis of drug
craving: an incentive-sensitization theory of addiction". Brain
Brain Research Reviews. 18 (3): 247–91.
doi:10.1016/0165-0173(93)90013-p. PMID 8401595.
^ Wright JS, Panksepp J (2012). "An evolutionary framework to
understand foraging, wanting, and desire: the neuropsychology of the
SEEKING system" (PDF). Neuropsychoanalysis. 14 (1): 5–39.
doi:10.1080/15294145.2012.10773683. Retrieved 24 September 2015.
^ a b c d e f g Malenka RC, Nestler EJ, Hyman SE (2009). Sydor A,
Brown RY, eds. Molecular Neuropharmacology: A Foundation for Clinical
Neuroscience (2nd ed.). New York: McGraw-Hill Medical.
pp. 147–148, 366–367, 375–376.
^ a b c d e Berridge KC, Robinson TE, Aldridge JW (February 2009).
"Dissecting components of reward: 'liking', 'wanting', and learning".
Current Opinion in Pharmacology. 9 (1): 65–73.
doi:10.1016/j.coph.2008.12.014. PMC 2756052 .
^ Bromberg-Martin ES, Matsumoto M, Hikosaka O (December 2010).
Dopamine in motivational control: rewarding, aversive, and alerting".
Neuron. 68 (5): 815–34. doi:10.1016/j.neuron.2010.11.022.
PMC 3032992 . PMID 21144997.
^ Yager LM, Garcia AF, Wunsch AM, Ferguson SM (August 2015). "The ins
and outs of the striatum: Role in drug addiction". Neuroscience. 301:
PMC 4523218 . PMID 26116518.
^ a b Saddoris MP, Cacciapaglia F, Wightman RM, Carelli RM (August
Dopamine Release Dynamics in the Nucleus
Accumbens Core and Shell Reveal Complementary Signals for Error
Prediction and Incentive Motivation". The Journal of Neuroscience. 35
(33): 11572–82. doi:10.1523/JNEUROSCI.2344-15.2015.
PMC 4540796 . PMID 26290234.
^ Berridge KC, Kringelbach ML (May 2015). "
Pleasure systems in the
brain". Neuron. 86 (3): 646–64. doi:10.1016/j.neuron.2015.02.018.
PMC 4425246 . PMID 25950633.
^ a b c Wise RA (1996). "Addictive drugs and brain stimulation
reward". Annual Review of Neuroscience. 19: 319–40.
doi:10.1146/annurev.ne.19.030196.001535. PMID 8833446.
^ Wise RA (October 2008). "
Dopamine and reward: the anhedonia
hypothesis 30 years on".
Neurotoxicity Research. 14 (2–3): 169–83.
doi:10.1007/BF03033808. PMC 3155128 . PMID 19073424.
^ Arias-Carrión O, Pöppel E (2007). "Dopamine, learning and
reward-seeking behavior". Acta Neurobiol Exp. 67 (4): 481–488.
^ Salamone JD, Correa M, Mingote S, Weber SM (April 2003). "Nucleus
accumbens dopamine and the regulation of effort in food-seeking
behavior: implications for studies of natural motivation, psychiatry,
and drug abuse". The Journal of Pharmacology and Experimental
Therapeutics. 305 (1): 1–8. doi:10.1124/jpet.102.035063.
^ a b Missale C, Nash SR, Robinson SW, Jaber M, Caron MG (January
Dopamine receptors: from structure to function". Physiological
Reviews. 78 (1): 189–225. doi:10.1152/physrev.19188.8.131.52.
^ a b Buttarelli FR, Fanciulli A, Pellicano C, Pontieri FE (June
2011). "The dopaminergic system in peripheral blood lymphocytes: from
physiology to pharmacology and potential applications to
neuropsychiatric disorders". Current Neuropharmacology. 9 (2):
278–88. doi:10.2174/157015911795596612. PMC 3131719 .
^ a b Sarkar C, Basu B, Chakroborty D, Dasgupta PS, Basu S (May 2010).
"The immunoregulatory role of dopamine: an update". Brain, Behavior,
and Immunity. 24 (4): 525–8. doi:10.1016/j.bbi.2009.10.015.
PMC 2856781 . PMID 19896530.
^ Hussain T, Lokhandwala MF (February 2003). "Renal dopamine receptors
and hypertension". Experimental Biology and Medicine. 228 (2):
134–42. doi:10.1177/153537020322800202. PMID 12563019.
^ Choi MR, Kouyoumdzian NM, Rukavina Mikusic NL, Kravetz MC, Rosón
MI, Rodríguez Fermepin M, Fernández BE (May 2015). "Renal
dopaminergic system: Pathophysiological implications and clinical
perspectives". World Journal of Nephrology. 4 (2): 196–212.
doi:10.5527/wjn.v4.i2.196. PMC 4419129 .
^ Carey RM (September 2001). "Theodore Cooper Lecture: Renal dopamine
system: paracrine regulator of sodium homeostasis and blood pressure".
Hypertension. 38 (3): 297–302. doi:10.1161/hy0901.096422.
^ a b c d e Rubí B, Maechler P (December 2010). "Minireview: new
roles for peripheral dopamine on metabolic control and tumor growth:
let's seek the balance". Endocrinology. 151 (12): 5570–81.
doi:10.1210/en.2010-0745. PMID 21047943.
^ "WHO Model List of Essential Medicines" (PDF). World Health
Organization. October 2013. Retrieved 24 September 2015.
^ Noori S, Friedlich P, Seri I (2003). "Pharmacology Review
Developmentally Regulated Cardiovascular, Renal, and Neuroendocrine
Effects of Dopamine" (PDF). NeoReviews. 4 (10): e283–e288.
doi:10.1542/neo.4-10-e283. Retrieved 24 September 2015.
^ a b Bhatt-Mehta V, Nahata MC (1989). "
Dopamine and dobutamine in
pediatric therapy". Pharmacotherapy. 9 (5): 303–14.
doi:10.1002/j.1875-9114.1989.tb04142.x. PMID 2682552.
^ a b c Bronwen JB, Knights KM (2009). Pharmacology for Health
Professionals (2nd ed.). Elsevier Australia. p. 192.
^ De Backer D, Biston P, Devriendt J, Madl C, Chochrad D, Aldecoa C,
Brasseur A, Defrance P, Gottignies P, Vincent JL (March 2010).
"Comparison of dopamine and norepinephrine in the treatment of shock".
The New England Journal of Medicine. 362 (9): 779–89.
doi:10.1056/NEJMoa0907118. PMID 20200382.
^ Karthik S, Lisbon A (2006). "Low-dose dopamine in the intensive care
unit". Seminars in Dialysis. 19 (6): 465–71.
doi:10.1111/j.1525-139X.2006.00208.x. PMID 17150046.
^ Moses, Scott. "Dopamine". Family Practice Notebook. Retrieved 1
^ Katritsis DG, Gersh BJ, Camm AJ (19 September 2013). Clinical
Cardiology: Current Practice Guidelines. OUP Oxford.
Dopamine binds to beta-1, beta-2, alpha-1
and dopaminergic receptors
^ Lewis RJ (2004). Sax's Dangerous Properties of Industrial Materials
(11th ed.). Hoboken, NJ.: Wiley & Sons. p. 1552.
^ Deng WP, Wong KA, Kirk KL (2002). "Convenient syntheses of 2-, 5-
and 6-fluoro- and 2,6-difluoro-L-DOPA". Tetrahedron: Asymmetry. 13
(11): 1135–1140. doi:10.1016/S0957-4166(02)00321-X.
^ Standaert DG, Walsh RR (2011). "Pharmacology of dopaminergic
neurotransmission". In Tashjian AH, Armstrong EJ, Golan DE. Principles
of Pharmacology: The Pathophysiologic Basis of Drug Therapy.
Lippincott Williams & Wilkins. pp. 186–206.
^ Mobbs CV, Hof PR (2009). Handbook of the neuroscience of aging.
Amsterdam: Elsevier/Academic Press. ISBN 978-0-12-374898-0.
^ Ota M, Yasuno F, Ito H, Seki C, Nozaki S, Asada T, Suhara T (July
2006). "Age-related decline of dopamine synthesis in the living human
brain measured by positron emission tomography with L-[beta-11C]DOPA".
Life Sciences. 79 (8): 730–6. doi:10.1016/j.lfs.2006.02.017.
^ Kaasinen V, Vilkman H, Hietala J, Någren K, Helenius H, Olsson H,
Farde L, Rinne J (2000). "Age-related dopamine D2/D3 receptor loss in
extrastriatal regions of the human brain". Neurobiology of Aging. 21
(5): 683–8. doi:10.1016/S0197-4580(00)00149-4.
^ Wang Y, Chan GL, Holden JE, Dobko T, Mak E, Schulzer M, Huser JM,
Snow BJ, Ruth TJ, Calne DB, Stoessl AJ (September 1998).
"Age-dependent decline of dopamine D1 receptors in human brain: a PET
study". Synapse. 30 (1): 56–61.
^ a b Wong DF, Wagner HN, Dannals RF, Links JM, Frost JJ, Ravert HT,
Wilson AA, Rosenbaum AE, Gjedde A, Douglass KH (December 1984).
"Effects of age on dopamine and serotonin receptors measured by
positron tomography in the living human brain". Science. 226 (4681):
1393–6. doi:10.1126/science.6334363. PMID 6334363.
^ a b Wang E, Snyder SD (1998). Handbook of the aging brain. San
Diego, California: Academic Press. ISBN 978-0-12-734610-6.
^ Chang L, Jiang CS, Ernst T (January 2009). "Effects of age and sex
on brain glutamate and other metabolites". Magnetic Resonance Imaging.
27 (1): 142–5. doi:10.1016/j.mri.2008.06.002. PMC 3164853 .
^ Dickson DV (2007). "Neuropathology of movement disorders". In Tolosa
E, Jankovic JJ.
Parkinson's disease and movement disorders.
Hagerstown, MD: Lippincott Williams & Wilkins. pp. 271–83.
^ a b Tuite PJ, Krawczewski K (April 2007). "Parkinsonism: a
review-of-systems approach to diagnosis". Seminars in Neurology. 27
(2): 113–22. doi:10.1055/s-2007-971174. PMID 17390256.
^ a b Olsen CM (December 2011). "Natural rewards, neuroplasticity, and
non-drug addictions". Neuropharmacology. 61 (7): 1109–22.
doi:10.1016/j.neuropharm.2011.03.010. PMC 3139704 .
^ Ceravolo R, Frosini D, Rossi C, Bonuccelli U (November 2010).
"Spectrum of addictions in Parkinson's disease: from dopamine
dysregulation syndrome to impulse control disorders". Journal of
Neurology. 257 (Suppl 2): S276–83. doi:10.1007/s00415-010-5715-0.
^ a b c d e f g Ghodse H (2010). Ghodse's Drugs and Addictive
Behaviour: A Guide to Treatment (4th ed.). Cambridge University Press.
pp. 87–92. ISBN 978-1-139-48567-8.
^ Heal DJ, Pierce DM (2006). "
Methylphenidate and its isomers: their
role in the treatment of attention-deficit hyperactivity disorder
using a transdermal delivery system". CNS Drugs. 20 (9): 713–38.
doi:10.2165/00023210-200620090-00002. PMID 16953648.
^ a b Freye E (2009). Pharmacology and abuse of cocaine, amphetamines,
ecstasy and related designer drugs a comprehensive review on their
mode of action, treatment of abuse and intoxication. Dordrecht:
Springer. ISBN 978-90-481-2448-0.
^ a b c Kimko HC, Cross JT, Abernethy DR (December 1999).
"Pharmacokinetics and clinical effectiveness of methylphenidate".
Clinical Pharmacokinetics. 37 (6): 457–70.
doi:10.2165/00003088-199937060-00002. PMID 10628897.
^ Mignot EJ (October 2012). "A practical guide to the therapy of
narcolepsy and hypersomnia syndromes". Neurotherapeutics. 9 (4):
739–52. doi:10.1007/s13311-012-0150-9. PMC 3480574 .
^ Zimmerman JL (October 2012). "
Cocaine intoxication". Critical Care
Clinics. 28 (4): 517–26. doi:10.1016/j.ccc.2012.07.003.
^ Nutt DJ, Lingford-Hughes A, Erritzoe D, Stokes PR (May 2015). "The
dopamine theory of addiction: 40 years of highs and lows". Nature
Reviews. Neuroscience. 16 (5): 305–12. doi:10.1038/nrn3939.
^ a b c Sinha R (August 2013). "The clinical neurobiology of drug
craving". Current Opinion in Neurobiology. 23 (4): 649–54.
doi:10.1016/j.conb.2013.05.001. PMC 3735834 .
^ Volkow ND, Baler RD (January 2014). "
Addiction science: Uncovering
neurobiological complexity". Neuropharmacology. 76 Pt B: 235–49.
doi:10.1016/j.neuropharm.2013.05.007. PMC 3818510 .
^ Nestler EJ (December 2012). "Transcriptional mechanisms of drug
addiction". Clinical Psychopharmacology and Neuroscience. 10 (3):
136–43. doi:10.9758/cpn.2012.10.3.136. PMC 3569166 .
^ Yeo BT, Krienen FM, Sepulcre J, Sabuncu MR, Lashkari D, Hollinshead
M, Roffman JL, Smoller JW, Zöllei L, Polimeni JR, Fischl B, Liu H,
Buckner RL (September 2011). "The organization of the human cerebral
cortex estimated by intrinsic functional connectivity". Journal of
Neurophysiology. 106 (3): 1125–65. doi:10.1152/jn.00338.2011.
PMC 3174820 . PMID 21653723.
^ a b c d e f g Healy D (2004). The Creation of Psychopharmacology.
Harvard University Press. pp. 37–73.
^ a b Brunton L. Goodman and Gilman's The Pharmacological Basis of
Therapeutics (12th ed.). McGraw Hill. pp. 417–455.
^ a b c d e Howes OD, Kapur S (May 2009). "The dopamine hypothesis of
schizophrenia: version III--the final common pathway". Schizophrenia
Bulletin. 35 (3): 549–62. doi:10.1093/schbul/sbp006.
PMC 2669582 . PMID 19325164.
^ Horacek J, Bubenikova-Valesova V, Kopecek M, Palenicek T, Dockery C,
Mohr P, Höschl C (2006). "Mechanism of action of atypical
antipsychotic drugs and the neurobiology of schizophrenia". CNS Drugs.
20 (5): 389–409. doi:10.2165/00023210-200620050-00004.
^ a b c James, Adam (2 March 2008). "Myth of the antipsychotic". The
Guardian. Guardian News and Media Limited. Retrieved 24 September
^ a b c Muench J, Hamer AM (March 2010). "Adverse effects of
antipsychotic medications". American Family Physician. 81 (5):
617–22. PMID 20187598.
^ Lambert M, Schimmelmann BG, Karow A, Naber D (November 2003).
"Subjective well-being and initial dysphoric reaction under
antipsychotic drugs - concepts, measurement and clinical relevance".
Pharmacopsychiatry. 36 Suppl 3 (Suppl 3): S181–90.
doi:10.1055/s-2003-45128. PMID 14677077.
^ a b Malenka RC, Nestler EJ, Hyman SE (2009). "Chapters 10 and 13".
In Sydor A, Brown RY. Molecular Neuropharmacology: A Foundation for
Clinical Neuroscience (2nd ed.). New York: McGraw-Hill Medical.
pp. 266, 318–323. ISBN 978-0-07-148127-4.
^ Wu J, Xiao H, Sun H, Zou L, Zhu LQ (June 2012). "Role of dopamine
receptors in ADHD: a systematic meta-analysis". Molecular
Neurobiology. 45 (3): 605–20. doi:10.1007/s12035-012-8278-5.
^ a b Berridge CW, Devilbiss DM (June 2011). "Psychostimulants as
cognitive enhancers: the prefrontal cortex, catecholamines, and
attention-deficit/hyperactivity disorder". Biological Psychiatry. 69
(12): e101–11. doi:10.1016/j.biopsych.2010.06.023.
PMC 3012746 . PMID 20875636.
^ Spencer RC, Devilbiss DM, Berridge CW (June 2015). "The
cognition-enhancing effects of psychostimulants involve direct action
in the prefrontal cortex". Biological Psychiatry. 77 (11): 940–50.
doi:10.1016/j.biopsych.2014.09.013. PMC 4377121 .
^ Ilieva IP, Hook CJ, Farah MJ (June 2015). "Prescription Stimulants'
Effects on Healthy Inhibitory Control, Working Memory, and Episodic
Memory: A Meta-analysis". Journal of Cognitive Neuroscience. 27 (6):
1069–89. doi:10.1162/jocn_a_00776. PMID 25591060.
^ a b c Wood PB (May 2008). "Role of central dopamine in pain and
analgesia". Expert Review of Neurotherapeutics. 8 (5): 781–97.
doi:10.1586/14737184.108.40.2061. PMID 18457535.
^ a b c d Flake ZA, Scalley RD, Bailey AG (March 2004). "Practical
selection of antiemetics". American Family Physician. 69 (5):
1169–74. PMID 15023018.
^ Connolly BS, Lang AE (2014). "Pharmacological treatment of Parkinson
disease: a review". JAMA. 311 (16): 1670–83.
doi:10.1001/jama.2014.3654. PMID 24756517.
^ Roshchina VV (2010). "Evolutionary considerations of
neurotransmitters in microbial, plant, and animal cells". In Lyte M,
Primrose PE. Microbial Endocrinology. New York: Springer.
pp. 17–52. ISBN 978-1-4419-5576-0.
^ a b Iyer LM, Aravind L, Coon SL, Klein DC, Koonin EV (July 2004).
"Evolution of cell-cell signaling in animals: did late horizontal gene
transfer from bacteria have a role?". Trends in Genetics. 20 (7):
292–9. doi:10.1016/j.tig.2004.05.007. PMID 15219393.
^ a b c d e Barron AB, Søvik E, Cornish JL (2010). "The roles of
dopamine and related compounds in reward-seeking behavior across
animal phyla". Frontiers in Behavioral Neuroscience. 4: 163.
doi:10.3389/fnbeh.2010.00163. PMC 2967375 .
^ Liu H, Mishima Y, Fujiwara T, Nagai H, Kitazawa A, Mine Y, et al.
(2004). "Isolation of Araguspongine M, a new stereoisomer of an
Araguspongine/Xestospongin alkaloid, and dopamine from the marine
sponge Neopetrosia exigua collected in Palau". Marine Drugs. 2 (4):
^ Kass-Simon G, Pierobon P (January 2007). "
neurotransmission, an updated overview". Comparative Biochemistry and
Physiology. Part A, Molecular & Integrative Physiology. 146 (1):
9–25. doi:10.1016/j.cbpa.2006.09.008. PMID 17101286.
^ Cottrell GA (January 1967). "Occurrence of dopamine and
noradrenaline in the nervous tissue of some invertebrate species".
British Journal of Pharmacology and Chemotherapy. 29 (1): 63–9.
doi:10.1111/j.1476-5381.1967.tb01939.x. PMC 1557178 .
^ Kindt KS, Quast KB, Giles AC, De S, Hendrey D, Nicastro I, Rankin
CH, Schafer WR (August 2007). "
Dopamine mediates context-dependent
modulation of sensory plasticity in C. elegans". Neuron. 55 (4):
662–76. doi:10.1016/j.neuron.2007.07.023. PMID 17698017.
^ a b Waddell S (June 2013). "
Reinforcement signalling in Drosophila;
dopamine does it all after all". Current Opinion in Neurobiology. 23
(3): 324–9. doi:10.1016/j.conb.2013.01.005. PMC 3887340 .
^ a b c d e f Kulma A, Szopa J (2007). "Catecholamines are active
compounds in plants". Plant Science. 172 (3): 433–440.
^ a b Ingle PK (2003). "
L-DOPA bearing plants" (PDF). Natural Product
Radiance. 2: 126–133. Retrieved 24 September 2015.
^ Wichers HJ, Visser JF, Huizing HJ, Pras N (1993). "Occurrence of
L-DOPA and dopamine in plants and cell cultures of
Mucuna pruriens and
effects of 2, 4-d and NaCl on these compounds". Plant Cell, Tissue and
Organ Culture. 33 (3): 259–264. doi:10.1007/BF02319010.
^ Longo R, Castellani A, Sberze P, Tibolla M (1974). "Distribution of
l-dopa and related amino acids in Vicia". Phytochemistry. 13 (1):
^ Van Alstyne KL, Nelson AV, Vyvyan JR, Cancilla DA (June 2006).
Dopamine functions as an antiherbivore defense in the temperate green
alga Ulvaria obscura". Oecologia. 148 (2): 304–11.
doi:10.1007/s00442-006-0378-3. PMID 16489461.
^ a b c Simon JD, Peles D, Wakamatsu K, Ito S (October 2009). "Current
challenges in understanding melanogenesis: bridging chemistry,
biological control, morphology, and function". Pigment Cell &
Melanoma Research. 22 (5): 563–79.
doi:10.1111/j.1755-148X.2009.00610.x. PMID 19627559.
^ Fedorow H, Tribl F, Halliday G, Gerlach M, Riederer P, Double KL
(February 2005). "
Neuromelanin in human dopamine neurons: comparison
with peripheral melanins and relevance to Parkinson's disease".
Progress in Neurobiology. 75 (2): 109–24.
doi:10.1016/j.pneurobio.2005.02.001. PMID 15784302.
^ Andrews RS, Pridham JB (1967). "Melanins from DOPA-containing
plants". Phytochemistry. 6 (1): 13–18.
^ Beldade P, Brakefield PM (June 2002). "The genetics and evo-devo of
butterfly wing patterns". Nature Reviews. Genetics. 3 (6): 442–52.
doi:10.1038/nrg818. PMID 12042771.
^ Fahn S (2008). "The history of dopamine and levodopa in the
treatment of Parkinson's disease". Movement Disorders. 23 Suppl 3:
S497–508. doi:10.1002/mds.22028. PMID 18781671.
^ Benes FM (January 2001). "Carlsson and the discovery of dopamine".
Trends in Pharmacological Sciences. 22 (1): 46–7.
doi:10.1016/S0165-6147(00)01607-2. PMID 11165672.
^ Barondes SH (2003). Better Than Prozac. New York: Oxford University
Press. pp. 21–22, 39–40. ISBN 978-0-19-515130-5.
^ Lee H, Dellatore SM, Miller WM, Messersmith PB (October 2007).
"Mussel-inspired surface chemistry for multifunctional coatings".
Science. 318 (5849): 426–30. Bibcode:2007Sci...318..426L.
doi:10.1126/science.1147241. PMC 2601629 .
^ a b Dreyer DR, Miller DJ, Freeman BD, Paul DR, Bielawski CW (2013).
"Perspectives on poly(dopamine)". Chemical Sciences. 4: 3796.
^ a b c d e Lynge ME, van der Westen R, Postma A, Städler B (December
2011). "Polydopamine--a nature-inspired polymer coating for biomedical
science" (PDF). Nanoscale. 3 (12): 4916–28.
PMID 22024699. Archived from the original (PDF) on 7 March
The dictionary definition of
Dopamine at Wiktionary
Major excitatory/inhibitory systems:
Glutamate system: Agmatine
Aspartic acid (aspartate)
Glutamic acid (glutamate)
Serine; GABA system: GABA
Glycine system: α-Alanine
Taurine; GHB system: GHB
Biogenic amines: Monoamines: 6-OHM
Serotonin (5-HT); Trace amines: 3-Iodothyronamine
p-Tyramine; Others: Histamine
Neuropeptides: See here instead.
2-AGE (noladin ether)
Neurosteroids: See here instead.
Adenosine system: Adenosine
Cholinergic system: Acetylcholine
Carbon monoxide (CO)
Hydrogen sulfide (H2S)
Nitric oxide (NO); Candidates: Acetaldehyde
Carbonyl sulfide (COS)
Nitrous oxide (N2O)
Sulfur dioxide (SO2)
Cardiac stimulants excluding cardiac glycosides (C01C)
Phosphodiesterase inhibitors (PDE3I)
Other cardiac stimulants
‡Withdrawn from market
§Never to phase III
Dopamine receptor modulators
Dihydrexidine derivatives: A-77636
Adrogolide (ABT-431, DAS-431)
Deoxyepinephrine (N-methyldopamine, epinine)
Typical antipsychotics: Butaclamol
Flupentixol (flupenthixol) (+melitracen)
Atypical antipsychotics: Asenapine
Dihydrexidine derivatives: 2-OH-NPA
Deoxyepinephrine (N-methyldopamine, epinine)
Typical antipsychotics: Acepromazine
Flupentixol (flupenthixol) (+melitracen)
Atypical antipsychotics: Amisulpride
See also: Receptor/signaling modulators
Monoamine reuptake inhibitors
Monoamine releasing agents
Monoamine metabolism modulators
Human trace amine-associated receptor ligands
Classical monoamine neurotransmitters
† References for all endogenous human
TAAR1 ligands are provided at
List of trace amines
‡ References for synthetic
TAAR1 agonists can be found at
in the associated compound articles. For
TAAR5 agonists and
inverse agonists, see TAAR for references.
See also: Receptor/signaling modulators
Amphetamine (Dextroamphetamine, Levoamphetamine)
Fenfluramine (Dexfenfluramine, Levofenfluramine)
Methamphetamine (Dextromethamphetamine, Levomethamphetamine)
Selegiline (also D -Deprenyl)
(and close relatives)
D -DOPA (Dextrodopa)
L -DOPA (Levodopa)
L -DOPS (Droxidopa)
Lysergic acid amide
Lysergic acid 2-butyl amide
Lysergic acid 2,4-dimethylazetidide
Lysergic acid diethylamide