A dopamine agonist is a compound that activates
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 ...
receptors. There are two families of
dopamine receptors
Dopamine receptors are a class of G protein-coupled receptors that are prominent in the vertebrate central nervous system (CNS). Dopamine receptors activate different effectors through not only G-protein coupling, but also signaling through diff ...
, D
1-like and D
2-like. They are all
G protein-coupled receptors
G protein-coupled receptors (GPCRs), also known as seven-(pass)-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptors, and G protein-linked receptors (GPLR), form a large protein family, group of evoluti ...
. D
1- and D
5-receptors belong to the
D1-like family and the
D2-like family includes D
2, D
3 and D
4 receptors.
Dopamine agonists are primarily used in the treatment of the motor symptoms 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 ...
, and to a lesser extent, in
hyperprolactinemia
Hyperprolactinaemia (also spelled hyperprolactinemia) is a condition characterized by abnormally high levels of prolactin in the blood. In women, normal prolactin levels average to about 13 ng/mL, while in men, they average 5 ng/mL. ...
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 ...
.
They are also used off-label in the treatment of
clinical depression
Major depressive disorder (MDD), also known as clinical depression, is a mental disorder characterized by at least two weeks of pervasive low mood, low self-esteem, and loss of interest or pleasure in normally enjoyable activities. Intro ...
.
Impulse control disorder
Impulse-control disorder (ICD) is a class of mental disorder, psychiatric disorders characterized by impulsivity – failure to resist a temptation, an urge, or an impulse; or having the inability to not speak on a thought.
The fifth edition of ...
s are associated with the use of dopamine agonists.
Medical uses
Parkinson's disease
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 ...
agonist
An agonist is a chemical that activates a Receptor (biochemistry), receptor to produce a biological response. Receptors are Cell (biology), cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an R ...
s are mainly 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 ...
.
The cause of Parkinson's is not fully known but genetic factors, for example specific
genetic mutations
In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, mitosi ...
, and environmental triggers have been linked to the disease. In Parkinson's disease
dopaminergic neurons
Dopaminergic cell groups, DA cell groups, or dopaminergic nuclei are collections of neurons in the central nervous system that synthesize the neurotransmitter dopamine. In the 1960s, dopaminergic neurons or ''dopamine neurons'' were first identi ...
that produce the
neurotransmitter
A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a Chemical synapse, synapse. The cell receiving the signal, or target cell, may be another neuron, but could also be a gland or muscle cell.
Neurotra ...
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 ...
in the brain slowly break down and can eventually die. With decreasing levels of dopamine the brain can't function properly and causes abnormal brain activity, which ultimately leads to the symptoms of Parkinson's disease.

There are two fundamental ways of treating Parkinson's disease, either by replacing dopamine or mimicking its effect.
Dopamine agonists act directly on the dopamine receptors and mimic dopamine's effect.
Dopamine agonists have two subclasses:
ergoline
Ergoline is a core structure in many alkaloids and their synthetic derivatives. Ergoline alkaloids were first characterized in ergot. Some of these are implicated in the condition of ergotism, which can take a convulsive form or a gangrenous for ...
and non-ergoline agonists. Both subclasses target dopamine D
2-type receptors. Types of ergoline agonists are
cabergoline
Cabergoline, sold under the brand name Dostinex among others, is a dopaminergic medication used in the treatment of high prolactin levels, prolactinomas, Parkinson's disease, and for other indications. It is taken by mouth.
Cabergoline is an ...
and
bromocriptine
Bromocriptine, originally marketed as Parlodel and subsequently under many brand names, is an ergoline derivative and dopamine agonist that is used in the treatment of pituitary tumors, Parkinson's disease, hyperprolactinaemia, neuroleptic malig ...
and examples of non-ergoline agonists are
pramipexole,
ropinirole and
rotigotine. Ergoline agonists are much less used nowadays because of the risk of
cartilage
Cartilage is a resilient and smooth type of connective tissue. Semi-transparent and non-porous, it is usually covered by a tough and fibrous membrane called perichondrium. In tetrapods, it covers and protects the ends of long bones at the joints ...
formation in heart valves.
Treatment of depression in Parkinson's patients
Depressive symptoms
Depression is a mental state of low mood and aversion to activity. It affects about 3.5% of the global population, or about 280 million people worldwide, as of 2020. Depression affects a person's thoughts, behavior, feelings, and sense o ...
and disorders are common in patients with Parkinson's disease and can affect their quality of life.
Increased anxiety can accentuate the symptoms of Parkinson's and is therefore essential to treat. Instead of conventional antidepressant medication in treating depression, treatment with dopamine agonists has been suggested.
It is mainly thought that dopamine agonists help with treating depressive symptoms and disorders by alleviating motor complications, which is one of the main symptoms of Parkinson's disease. Although preliminary evidence of clinical trials has shown interesting results, further research odds crucial to establish the anti-depressive effects of dopamine agonists in treating depressive symptoms and disorders in those with Parkinson's.
Hyperprolactinemia
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 ...
is a prolactin-inhibiting factor (PIFs) since it lowers the prolactin-releasing factors (PRFs) synthesis and secretion through D
2-like receptors. That is why dopamine agonists are the first-line treatment in
hyperprolactinaemia
Hyperprolactinaemia (also spelled hyperprolactinemia) is a condition characterized by abnormally high levels of prolactin in the blood. In women, normal prolactin levels average to about 13 ng/mL, while in men, they average 5 ng/mL. ...
. Ergoline-derived agents,
bromocriptine
Bromocriptine, originally marketed as Parlodel and subsequently under many brand names, is an ergoline derivative and dopamine agonist that is used in the treatment of pituitary tumors, Parkinson's disease, hyperprolactinaemia, neuroleptic malig ...
and
cabergoline
Cabergoline, sold under the brand name Dostinex among others, is a dopaminergic medication used in the treatment of high prolactin levels, prolactinomas, Parkinson's disease, and for other indications. It is taken by mouth.
Cabergoline is an ...
are mostly used in treatment. Research shows that these agents reduce the size of
prolactinoma
A prolactinoma is a tumor (adenoma) of the pituitary gland that produces the hormone prolactin. It is the most common type of functioning pituitary tumor. Symptoms of prolactinoma are due to abnormally high levels of prolactin in the blood ( hyp ...
s by suppressing the hypersecretion of
prolactin
Prolactin (PRL), also known as lactotropin and mammotropin, is a protein best known for its role in enabling mammals to produce milk. It is influential in over 300 separate processes in various vertebrates, including humans. Prolactin is secr ...
resulting in normal
gonad
A gonad, sex gland, or reproductive gland is a Heterocrine gland, mixed gland and sex organ that produces the gametes and sex hormones of an organism. Female reproductive cells are egg cells, and male reproductive cells are sperm. The male gon ...
al function.
Restless leg syndrome
Numerous clinical trials have been performed to assess the use of dopamine agonists for the treatment of
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 ...
(RLS). RLS is identified by the strong urge to move and is a dopamine-dependent disorder. RLS symptoms decrease with the use of drugs that stimulate dopamine receptors and increase dopamine levels, such as dopamine agonists.
Adverse effects
Side effects
Dopamine agonists are mainly used to treat
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 ...
, but also
hyperprolactinemia
Hyperprolactinaemia (also spelled hyperprolactinemia) is a condition characterized by abnormally high levels of prolactin in the blood. In women, normal prolactin levels average to about 13 ng/mL, while in men, they average 5 ng/mL. ...
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 side effects are predominantly collected from studies of Parkinson's disease, where dopamine agonists are commonly used as a first-line treatment with
levodopa
Levodopa, also known as L-DOPA and sold under many brand names, is a dopaminergic medication which is used in the treatment of Parkinson's disease (PD) and certain other conditions like dopamine-responsive dystonia and restless legs syndrome. ...
.
Dopamine agonists are divided into two subgroups or drug classes, first-generation and newer agents. Ergoline derived agonists comprise the first generation; more widely used today are the non-ergoline derived agents. Ergoline derived agonists are generally less selective and tend to show interactions with receptors other than dopamine receptors, which can cause more side effects.
Bromocriptine
Bromocriptine, originally marketed as Parlodel and subsequently under many brand names, is an ergoline derivative and dopamine agonist that is used in the treatment of pituitary tumors, Parkinson's disease, hyperprolactinaemia, neuroleptic malig ...
,
cabergoline
Cabergoline, sold under the brand name Dostinex among others, is a dopaminergic medication used in the treatment of high prolactin levels, prolactinomas, Parkinson's disease, and for other indications. It is taken by mouth.
Cabergoline is an ...
,
pergolide
Pergolide, sold under the brand name Permax and Prascend (veterinary) among others, is an ergoline-based dopamine receptor agonist used in some countries for the treatment of Parkinson's disease. Parkinson's disease is associated with reduced do ...
and
lisuride are examples of ergoline derived agonists. Non-ergoline agonists include
pramipexole,
ropinirole,
rotigotine,
piribedil and
apomorphine.
The most common adverse effects are
constipation
Constipation is a bowel dysfunction that makes bowel movements infrequent or hard to pass. The Human feces, stool is often hard and dry. Other symptoms may include abdominal pain, bloating, and feeling as if one has not completely passed the ...
,
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
headache
A headache, also known as cephalalgia, is the symptom of pain in the face, head, or neck. It can occur as a migraine, tension-type headache, or cluster headache. There is an increased risk of Depression (mood), depression in those with severe ...
s. Other serious side effects are
hallucination
A hallucination is a perception in the absence of an external stimulus that has the compelling sense of reality. They are distinguishable from several related phenomena, such as dreaming ( REM sleep), which does not involve wakefulness; pse ...
s,
peripheral edema
Peripheral edema is edema (accumulation of fluid causing swelling) in tissues perfused by the peripheral vascular system, usually in the lower limbs. In the most dependent parts of the body (those hanging distally), it may be called dependent ede ...
, gastrointestinal ulcers,
pulmonary fibrosis
Pulmonary fibrosis is a condition in which the lungs become scarred over time. Symptoms include shortness of breath, a dry cough, feeling tired, weight loss, and nail clubbing. Complications may include pulmonary hypertension, respiratory ...
and
psychosis
In psychopathology, psychosis is a condition in which a person is unable to distinguish, in their experience of life, between what is and is not real. Examples of psychotic symptoms are delusions, hallucinations, and disorganized or inco ...
.
Dopamine agonists have been linked to cardiac problems, with side effects such as
hypotension
Hypotension, also known as low blood pressure, is a cardiovascular condition characterized by abnormally reduced blood pressure. Blood pressure is the force of blood pushing against the walls of the arteries as the heart pumps out blood and is ...
,
myocardial infarction
A myocardial infarction (MI), commonly known as a heart attack, occurs when Ischemia, blood flow decreases or stops in one of the coronary arteries of the heart, causing infarction (tissue death) to the heart muscle. The most common symptom ...
, congestive heart failure, cardiac fibrosis,
pericardial effusion
A pericardial effusion is an abnormal accumulation of fluid in the pericardial cavity. The pericardium is a two-part membrane surrounding the heart: the outer fibrous Connective tissue, connective membrane and an inner two-layered serous membrane ...
and
tachycardia
Tachycardia, also called tachyarrhythmia, is a heart rate that exceeds the normal resting rate. In general, a resting heart rate over 100 beats per minute is accepted as tachycardia in adults. Heart rates above the resting rate may be normal ...
.
A high risk for
valvular heart disease
Valvular heart disease is any cardiovascular disease process involving one or more of the four valves of the heart (the aortic and mitral valves on the left side of heart and the pulmonic and tricuspid valves on the right side of heart). The ...
has been established in association with ergot-derived agonists especially in elderly patients with hypertension.
In some studies, almost 30% of patients are reported to have suffered from
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 sleep attacks when using dopamine agonists. Daytime sleepiness,
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 ...
and other sleep disturbances are also frequently associated with the use of these drugs.
Impulse control disorder
Impulse-control disorder (ICD) is a class of mental disorder, psychiatric disorders characterized by impulsivity – failure to resist a temptation, an urge, or an impulse; or having the inability to not speak on a thought.
The fifth edition of ...
, which manifests in behaviors such as gambling, hypersexuality, compulsive shopping or binge eating, can be another serious adverse effect of dopamine agonists.
After long-term use of dopamine agonists a
withdrawal syndrome
Withdrawal means "an act of taking out" and may refer to:
* Anchoresis (withdrawal from the world for religious or ethical reasons)
* '' Coitus interruptus'' (the withdrawal method)
* Drug withdrawal
A drug is any chemical substance other th ...
may occur when discontinuing the drug or reducing the dose. The following side effects are possible: anxiety, panic attacks,
dysphoria
Dysphoria (; ) is a profound state of unease or dissatisfaction. It is the semantic opposite of euphoria. In a psychiatric context, dysphoria may accompany depression, anxiety, or agitation.
In psychiatry
Intense states of distress and uneas ...
, depression, agitation, irritability, suicidal ideation, fatigue,
orthostatic hypotension
Orthostatic hypotension, also known as postural hypotension, is a medical condition wherein a person's blood pressure drops when they are standing up ( orthostasis) or sitting down. Primary orthostatic hypotension is also often referred to as ne ...
, nausea, vomiting,
diaphoresis
Perspiration, also known as sweat, is the fluid secreted by sweat glands in the skin of mammals.
Two types of sweat glands can be found in humans: eccrine glands and apocrine glands. The eccrine sweat glands are distributed over much of the ...
, generalised pain and drug cravings. For some individuals, these withdrawal symptoms are short-lived, and they make a full recovery. For others, a
protracted withdrawal syndrome may occur with symptoms persisting for months or years.
Interactions
Dopamine agonists
interact with a number of
drug
A drug is any chemical substance other than a nutrient or an essential dietary ingredient, which, when administered to a living organism, produces a biological effect. Consumption of drugs can be via insufflation (medicine), inhalation, drug i ...
s but there is little evidence that they
interact with other
Parkinson's
Parkinson's disease (PD), or simply Parkinson's, is a neurodegenerative disease primarily of the central nervous system, affecting both motor and non-motor systems. Symptoms typically develop gradually and non-motor issues become more prevalen ...
drugs. In most cases there is no reason not to co-administer Parkinson's drugs, but there have been indications that the concurrent use of dopamine agonists with
L-DOPA
-DOPA, also known as -3,4-dihydroxyphenylalanine and used medically as levodopa, is made and used as part of the normal biology of some plants and animals, including humans. Humans, as well as a portion of the other animals that utilize -DO ...
can cause
psychosis
In psychopathology, psychosis is a condition in which a person is unable to distinguish, in their experience of life, between what is and is not real. Examples of psychotic symptoms are delusions, hallucinations, and disorganized or inco ...
, and therefore in these cases it is recommended that either the dopamine agonist(s) be discontinued or the dose of
L-DOPA
-DOPA, also known as -3,4-dihydroxyphenylalanine and used medically as levodopa, is made and used as part of the normal biology of some plants and animals, including humans. Humans, as well as a portion of the other animals that utilize -DO ...
reduced. Since ergot-dopamine
agonist
An agonist is a chemical that activates a Receptor (biochemistry), receptor to produce a biological response. Receptors are Cell (biology), cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an R ...
have antihypertensive qualities it is wise to monitor
blood pressure
Blood pressure (BP) is the pressure of Circulatory system, circulating blood against the walls of blood vessels. Most of this pressure results from the heart pumping blood through the circulatory system. When used without qualification, the term ...
when using dopamine agonists with
antihypertensive
Antihypertensives are a class of drugs that are used to treat hypertension (high blood pressure). Antihypertensive therapy seeks to prevent the complications of high blood pressure, such as stroke, heart failure, kidney failure and myocardial infa ...
drugs to ensure that the patient does not get
hypotension
Hypotension, also known as low blood pressure, is a cardiovascular condition characterized by abnormally reduced blood pressure. Blood pressure is the force of blood pushing against the walls of the arteries as the heart pumps out blood and is ...
. That includes the drug
sildenafil
Sildenafil, sold under the brand name Viagra among others, is a medication used to treat erectile dysfunction and pulmonary hypertension, pulmonary arterial hypertension. It is also sometimes used off-label for the treatment of certain sym ...
which is commonly used to treat
erectile dysfunction
Erectile dysfunction (ED), also referred to as impotence, is a form of sexual dysfunction in males characterized by the persistent or recurring inability to achieve or maintain a Human penis, penile erection with sufficient rigidity and durat ...
but also used for
pulmonary hypertension
Pulmonary hypertension (PH or PHTN) is a condition of increased blood pressure in the pulmonary artery, arteries of the lungs. Symptoms include dypsnea, shortness of breath, Syncope (medicine), fainting, tiredness, chest pain, pedal edema, swell ...
.
There is evidence that suggests that since ergot dopamine agonists are
metabolized
Metabolism (, from ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cellular processes; the co ...
by
CYP3A4
Cytochrome P450 3A4 (abbreviated CYP3A4) () is an important enzyme in the body, mainly found in the liver and in the intestine, which in humans is encoded by ''CYP3A4'' gene. It organic redox reaction, oxidizes small foreign organic molecules ( ...
enzyme concentration rises with the use of CYP3A4 inhibitors. For example, in one study
bromocriptine
Bromocriptine, originally marketed as Parlodel and subsequently under many brand names, is an ergoline derivative and dopamine agonist that is used in the treatment of pituitary tumors, Parkinson's disease, hyperprolactinaemia, neuroleptic malig ...
was given with a CYP3A4 inhibitor and the
AUC (area under the curve) increased 268%.
Ropinirole is a non-ergot derived dopamine
agonist
An agonist is a chemical that activates a Receptor (biochemistry), receptor to produce a biological response. Receptors are Cell (biology), cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an R ...
and concomitant use with a CYP1A2 inhibitor can result in a higher concentration of ropinirole. When discontinuing the
CYP1A2
Cytochrome P450 1A2 (abbreviated CYP1A2), a member of the cytochrome P450 mixed-function oxidase system, is involved in the metabolism of xenobiotics in the human body. In humans, the CYP1A2 enzyme is encoded by the ''CYP1A2'' gene.
Function
...
inhibitor, if using both drugs, there is a chance that a dose adjustment for ropinirole is needed. There is also evidence the dopamine agonists inhibit various
CYP enzymes and therefore they may inhibit the metabolism of certain drugs.
Pharmacokinetics
Pharmacokinetics is the study of how a drug moves through the body, involving four main processes: absorption, distribution, metabolism, and excretion. Absorption refers to how the drug enters the bloodstream after administration. Distribution describes how the drug spreads throughout the body's tissues and organs. Metabolism involves the breakdown of the drug, typically in the liver. Finally, excretion is how the drug or its metabolites are eliminated from the body, often through urine or feces (Gibaldi & Perrier, 1982).
Ergolines
Bromocriptine
Absorption
Absorption may refer to:
Chemistry and biology
*Absorption (biology), digestion
**Absorption (small intestine)
*Absorption (chemistry), diffusion of particles of gas or liquid into liquid or solid materials
*Absorption (skin), a route by which su ...
of
bromocriptine
Bromocriptine, originally marketed as Parlodel and subsequently under many brand names, is an ergoline derivative and dopamine agonist that is used in the treatment of pituitary tumors, Parkinson's disease, hyperprolactinaemia, neuroleptic malig ...
oral dose is approximately 28%; however, only 6% reaches the systemic circulation unchanged, due to a substantial
first-pass effect. Bromocriptine reaches mean peak plasma levels after about 1–1.5 hours after a single oral dose. The drug has high
protein binding, ranging from 90-96% bound to serum
albumin
Albumin is a family of globular proteins, the most common of which are the serum albumins. All of the proteins of the albumin family are water- soluble, moderately soluble in concentrated salt solutions, and experience heat denaturation. Alb ...
. Bromocriptine is
metabolized
Metabolism (, from ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cellular processes; the co ...
by
CYP3A4
Cytochrome P450 3A4 (abbreviated CYP3A4) () is an important enzyme in the body, mainly found in the liver and in the intestine, which in humans is encoded by ''CYP3A4'' gene. It organic redox reaction, oxidizes small foreign organic molecules ( ...
and excreted primarily in the
feces
Feces (also known as faeces American and British English spelling differences#ae and oe, or fæces; : faex) are the solid or semi-solid remains of food that was not digested in the small intestine, and has been broken down by bacteria in the ...
via biliary secretion. Metabolites and parent drugs are mostly
excreted via the
liver
The liver is a major metabolic organ (anatomy), organ exclusively found in vertebrates, which performs many essential biological Function (biology), functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of var ...
, but also 6% via the
kidney
In humans, the kidneys are two reddish-brown bean-shaped blood-filtering organ (anatomy), organs that are a multilobar, multipapillary form of mammalian kidneys, usually without signs of external lobulation. They are located on the left and rig ...
. It has a
half-life Half-life is a mathematical and scientific description of exponential or gradual decay.
Half-life, half life or halflife may also refer to:
Film
* Half-Life (film), ''Half-Life'' (film), a 2008 independent film by Jennifer Phang
* ''Half Life: ...
of 2–8 hours.
Pergolide
Pergolide
Pergolide, sold under the brand name Permax and Prascend (veterinary) among others, is an ergoline-based dopamine receptor agonist used in some countries for the treatment of Parkinson's disease. Parkinson's disease is associated with reduced do ...
has a long half-life of about 27 hours and reaches a mean peak plasma level in about 2–3 hours after a single oral dose. The protein binding is 90% and the drug is mainly metabolized in the liver by CYP3A4 and
CYP2D6
Cytochrome P450 2D6 (CYP2D6) is an enzyme that in humans is encoded by the ''CYP2D6'' gene. ''CYP2D6'' is primarily expressed in the liver. It is also highly expressed in areas of the central nervous system, including the substantia nigra.
CYP2 ...
. The major route of excretion is through the kidneys.
Non-ergolines
Pramipexole
Pramipexole reaches maximum plasma concentration 1–3 hours post-dose. It is about 15% bound to plasma proteins and the metabolism is minimal. Pramipexole has a long half-life, around 27 hours. The drug is mostly excreted in the urine, around 90%, but also in feces.
Ropinirole
Ropinirole is rapidly absorbed after a single oral dose, reaching plasma concentration in approximately 1–2 hours. The half-life is around 5–6 hours. Ropinirole is heavily metabolized by the liver and
in vitro
''In vitro'' (meaning ''in glass'', or ''in the glass'') Research, studies are performed with Cell (biology), cells or biological molecules outside their normal biological context. Colloquially called "test-tube experiments", these studies in ...
studies show that 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 ...
involved in the metabolism of ropinirole is
CYP1A2
Cytochrome P450 1A2 (abbreviated CYP1A2), a member of the cytochrome P450 mixed-function oxidase system, is involved in the metabolism of xenobiotics in the human body. In humans, the CYP1A2 enzyme is encoded by the ''CYP1A2'' gene.
Function
...
.
Rotigotine
Since
rotigotine is a
transdermal patch
A transdermal patch is a medicated adhesive patch that is placed on the skin to deliver a specific Dose (biochemistry), dose of medication through the skin and into the bloodstream. An advantage of a transdermal drug delivery route over ot ...
it provides continuous drug delivery over 24 hours. It has a half-life of 3 hours and the protein binding is around 92% in vitro and 89.5%
in vivo
Studies that are ''in vivo'' (Latin for "within the living"; often not italicized in English) are those in which the effects of various biological entities are tested on whole, living organisms or cells, usually animals, including humans, an ...
. Rotigotine is extensively and rapidly metabolized in the liver and by the CYP enzymes. The drug is mostly excreted in urine (71%), but also in feces (23%).
Mechanism of action
The dopamine receptors are members of the
G protein-coupled receptor
G protein-coupled receptors (GPCRs), also known as seven-(pass)-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptors, and G protein-linked receptors (GPLR), form a large group of evolutionarily related ...
s superfamily with seven transmembrane domains. Dopamine receptors have five subtypes, D
1 through D
5, the subtypes can be divided into two subclasses due to their mechanism of action on
adenylate cyclase enzyme, D
1-like receptors (D
1 and D
5) and D
2-like receptors (D
2, D
3 and D
4). D
1-like receptors are primarily coupled to Gα
s/olf proteins and activates adenylate cyclase which increases intracellular levels of
cAMP
Camp may refer to:
Areas of confinement, imprisonment, or for execution
* Concentration camp, an internment camp for political prisoners or politically targeted demographics, such as members of national or minority ethnic groups
* Extermination ...
, they also activate the G
βγ complex and the
N-type Ca2+ channel. D
2-like receptors decrease intracellular levels of the second messenger cAMP by inhibiting adenylate cyclase.
Bromocriptine
Bromocriptine
Bromocriptine, originally marketed as Parlodel and subsequently under many brand names, is an ergoline derivative and dopamine agonist that is used in the treatment of pituitary tumors, Parkinson's disease, hyperprolactinaemia, neuroleptic malig ...
is an ergot derivative, semi-synthetic. Bromocriptine is a D
2 receptor agonist and D
1 receptor antagonist with a binding affinity to D
2 receptors of anterior pituitary cells, exclusively on lactotrophs. Bromocriptine stimulates Na
+, K
+-ATPase activity and/or cytosolic Ca
2+ elevation and therefore reduction of prolactin which leads to no production of cAMP.
Pramipexole
Pramipexole is a highly active non-ergot D
2-like receptor agonist with a higher binding affinity to D
3 receptors rather than D
2 or D
4 receptors. The mechanism of action of pramipexole is mostly unknown, it is thought to be involved in the activation of dopamine receptors in the area of the brain where the striatum and the substantia nigra is located. This stimulation of dopamine receptors in the striatum may lead to the better movement performance.
Structure–activity relationship
When dealing with agonists it can be extremely complex to confirm relationships between structure and biological activity. Agonists generate responses from
living tissues. Therefore, their activity depends both on their
efficacy
Efficacy is the ability to perform a task to a satisfactory or expected degree. The word comes from the same roots as '' effectiveness'', and it has often been used synonymously, although in pharmacology a distinction is now often made betwee ...
to activate receptors and their affinity to bind to receptors.
Crossing the blood brain barrier
Many molecules are unable to cross the
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 ...
(BBB). Molecules must be small,
non-polar
In chemistry, polarity is a separation of electric charge leading to a molecule or its chemical groups having an electric dipole moment, with a negatively charged end and a positively charged end.
Polar molecules must contain one or more polar ...
and
lipophilic
Lipophilicity (from Greek language, Greek λίπος "fat" and :wikt:φίλος, φίλος "friendly") is the ability of a chemical compound to dissolve in fats, oils, lipids, and non-polar solvents such as hexane or toluene. Such compounds are c ...
to cross over. Compounds without these qualities must have a specific transporter that can transport them over the BBB. Dopamine cannot diffuse across the BBB because of the
catechol
Catechol ( or ), also known as pyrocatechol or 1,2-dihydroxybenzene, is an organic compound with the molecular formula . It is the ''ortho'' isomer of the three isomeric benzenediols. This colorless compound occurs naturally in trace amounts. It ...
group, it is too polar and therefore unable to enter the brain. The catechol group is a dihydroxy
benzene
Benzene is an Organic compound, organic chemical compound with the Chemical formula#Molecular formula, molecular formula C6H6. The benzene molecule is composed of six carbon atoms joined in a planar hexagonal Ring (chemistry), ring with one hyd ...
ring.
The synthesis of dopamine consists of three stages. The synthesis process starts with an amino acid, called
-tyrosine. In the second stage
-DOPA (levodopa) is formed by adding a phenol group to the benzene ring of -tyrosine. The formation of -DOPA from L-tyrosine is catalyzed by the enzyme tyrosine hydroxylase. The third stage is the formation of dopamine by removing the carboxylic acid group from -DOPA, catalysed by the enzyme dopa decarboxylase.
Levodopa is also too polar to cross the blood brain barrier but it is an amino acid and has a specialized transporter called L-type amino acid transporter or
LAT-1 that helps it diffuse through the barrier.
Dopamine
When dopamine interacts with ATP, which is a component of some dopamine receptors, it has a significant preference for a trans-conformation of the dopamine molecule. The dopamine-ATP complex is stabilised by
hydrogen bond
In chemistry, a hydrogen bond (H-bond) is a specific type of molecular interaction that exhibits partial covalent character and cannot be described as a purely electrostatic force. It occurs when a hydrogen (H) atom, Covalent bond, covalently b ...
ing between catechol hydroxyls and purine nitrogens and by
electrostatic interactions
Electrostatics is a branch of physics that studies slow-moving or stationary electric charges.
Since classical times, it has been known that some materials, such as amber, attract lightweight particles after rubbing. The Greek word (), meani ...
between the protonated
ammonium
Ammonium is a modified form of ammonia that has an extra hydrogen atom. It is a positively charged (cationic) polyatomic ion, molecular ion with the chemical formula or . It is formed by the protonation, addition of a proton (a hydrogen nucleu ...
group of dopamine and a negative
phosphate
Phosphates are the naturally occurring form of the element phosphorus.
In chemistry, a phosphate is an anion, salt, functional group or ester derived from a phosphoric acid. It most commonly means orthophosphate, a derivative of orthop ...
group. Two conformers of dopamine have been identified as alpha- and beta-conformers in which the catechol ring is coplanar with the plane of the
ethylamine
Ethylamine, also known as ethanamine, is an organic compound with the chemical formula, formula CH3CH2NH2. This colourless gas has a strong ammonia-like odor. It condenses just below room temperature to a liquid miscibility, miscible with virtual ...
side chain. They are substantial in agonist-receptor interactions.
Ergoline derivatives
Central dopaminergic agonist properties of semisynthetic
ergoline
Ergoline is a core structure in many alkaloids and their synthetic derivatives. Ergoline alkaloids were first characterized in ergot. Some of these are implicated in the condition of ergotism, which can take a convulsive form or a gangrenous for ...
derivatives lergotrile,
pergolide
Pergolide, sold under the brand name Permax and Prascend (veterinary) among others, is an ergoline-based dopamine receptor agonist used in some countries for the treatment of Parkinson's disease. Parkinson's disease is associated with reduced do ...
,
bromocriptine
Bromocriptine, originally marketed as Parlodel and subsequently under many brand names, is an ergoline derivative and dopamine agonist that is used in the treatment of pituitary tumors, Parkinson's disease, hyperprolactinaemia, neuroleptic malig ...
and
lisuride have been established. Some studies suggest that ergot alkaloids have the properties of mixed agonist-antagonist with regards to certain presynaptic and postsynaptic receptors. N-n-
Propyl groups (chemical formula: –CH
2CH
2CH
3) frequently enhance dopamine agonist effects in the ergoline derivatives.

The (+)-
enantiomer
In chemistry, an enantiomer (Help:IPA/English, /ɪˈnænti.əmər, ɛ-, -oʊ-/ Help:Pronunciation respelling key, ''ih-NAN-tee-ə-mər''), also known as an optical isomer, antipode, or optical antipode, is one of a pair of molecular entities whi ...
displays notably diminished activity whereas the (-)-enantiomer possess potent dopamine agonist properties.
''Bromocriptine''
Bromocriptine
Bromocriptine, originally marketed as Parlodel and subsequently under many brand names, is an ergoline derivative and dopamine agonist that is used in the treatment of pituitary tumors, Parkinson's disease, hyperprolactinaemia, neuroleptic malig ...
has an ergot alkaloid structure. Ergot alkaloids are divided into 2 groups; amino acid ergot alkaloids and amine ergot alkaloids, bromocriptine is part of the former group. It contains a
bromine
Bromine is a chemical element; it has chemical symbol, symbol Br and atomic number 35. It is a volatile red-brown liquid at room temperature that evaporates readily to form a similarly coloured vapour. Its properties are intermediate between th ...
halogen
The halogens () are a group in the periodic table consisting of six chemically related elements: fluorine (F), chlorine (Cl), bromine (Br), iodine (I), and the radioactive elements astatine (At) and tennessine (Ts), though some authors would ...
on the ergot structure which increases the affinity for the D
2-receptor but often reduces the efficacy. The similarity between the dopamine structure and the ergoline ring in bromocriptine is likely the cause for its action on the dopamine receptors. It has shown to have equal affinity for D
2- and D
3-receptor and much lower affinity for D
1-receptor.
Non-ergoline derivatives
Non-ergoline dopamine receptor agonists have higher binding affinity to dopamine D
3-receptors than dopamine D
2-receptors. This binding affinity is related to D
2 and D
3 receptor homology, the homology between them has a high degree of sequence and is closest in their transmembrane domains, were they share around 75% of the amino acid.
''Apomorphine''
Apomorphine has a
catechol
Catechol ( or ), also known as pyrocatechol or 1,2-dihydroxybenzene, is an organic compound with the molecular formula . It is the ''ortho'' isomer of the three isomeric benzenediols. This colorless compound occurs naturally in trace amounts. It ...
element and belongs to a class called
β-phenylethylamines and its main components are similar to the dopamine structure. The effect that apomorphine has on the dopamine receptors can also be linked to the similarities between its structure and dopamine. It is a
chiral
Chirality () is a property of asymmetry important in several branches of science. The word ''chirality'' is derived from the Greek language, Greek (''kheir''), "hand", a familiar chiral object.
An object or a system is ''chiral'' if it is dist ...
molecule and thus can be acquired in both the R and S form, the R form is the one that is used in therapy. When apomorphine interacts with the dopamine receptor, or the
ATP on the receptor, the catechol and nitrogen are important to stabilize the structure with hydrogen bonding. The position of the hydroxyl groups is also important and monohydroxy derivatives have been found to be less potent than the dihydroxy groups. There are a number of stability concerns with apomorphine such as oxidation and racemization.
''Rotigotine''
Rotigotine is a phenolic amine and thus has poor oral bioavailability and fast clearance from the body. Therefore, it has been formulated as a
transdermal patch
A transdermal patch is a medicated adhesive patch that is placed on the skin to deliver a specific Dose (biochemistry), dose of medication through the skin and into the bloodstream. An advantage of a transdermal drug delivery route over ot ...
, first and foremost to prevent
first pass metabolism in the liver.
Members
Examples of dopamine agonists include:
Partial agonist
*
Aripiprazole
Aripiprazole, sold under the brand name Abilify, among others, is an atypical antipsychotic primarily used in the treatment of schizophrenia, bipolar disorder, and irritability associated with autism spectrum disorder; other uses include as ...
(Partial agonist of the D
2 family receptors - Trade name "Abilify" in the United States; atypical
antipsychotic
Antipsychotics, previously known as neuroleptics and major tranquilizers, are a class of Psychiatric medication, psychotropic medication primarily used to manage psychosis (including delusions, hallucinations, paranoia or disordered thought), p ...
)
*
Brexpiprazole
Brexpiprazole, sold under the brand name Rexulti among others, is an atypical antipsychotic medication used for the treatment of major depressive disorder, schizophrenia, and Agitation (dementia), agitation associated with dementia due to Alzhe ...
(Partial agonist of the D
2 family receptors - Trade name "Rexulti" in the United States; atypical
antipsychotic
Antipsychotics, previously known as neuroleptics and major tranquilizers, are a class of Psychiatric medication, psychotropic medication primarily used to manage psychosis (including delusions, hallucinations, paranoia or disordered thought), p ...
)
*
Cariprazine
Cariprazine, sold under the brand name Vraylar among others, is an atypical antipsychotic developed by Gedeon Richter, which is used in the treatment of schizophrenia and bipolar disorder. It is also prescribed as an add-on treatment for bip ...
(Partial agonist of the D
2 family receptors and D
3 receptor - Trade name "Vraylar" in the United States; atypical
antipsychotic
Antipsychotics, previously known as neuroleptics and major tranquilizers, are a class of Psychiatric medication, psychotropic medication primarily used to manage psychosis (including delusions, hallucinations, paranoia or disordered thought), p ...
)
*
Phencyclidine
Phencyclidine or phenylcyclohexyl piperidine (PCP), also known in its use as a street drug as angel dust among other names, is a dissociative anesthetic mainly used recreationally for its significant mind-altering effects. PCP may cause hall ...
(a.k.a. PCP; partial agonist. Psychoactivity mainly due to
NMDA antagonism)
*
Quinpirole (Partial agonist of the D
2 and D
3 family of receptors)
*
Salvinorin A
Salvinorin A is the main active psychotropic molecule in '' Salvia divinorum''. Salvinorin A is considered an atypical dissociative hallucinogen.
It is structurally distinct from other naturally occurring hallucinogens (such as DMT, psil ...
(chief active constituent of the psychedelic herb
salvia divinorum
''Salvia divinorum'' (; also called ska maría pastora, seer's sage, yerba de la pastora, magic mint or simply salvia) is a species of plant in the sage genus ''Salvia'', known for its transient psychoactive properties when its leaves, or e ...
, the psychoactivity of which is mainly due to
Kappa-opioid receptor agonism; partial agonist at the D
2 with an
Intrinsic activity
Intrinsic activity (IA) and efficacy (Emax) refer to the relative ability of a drug- receptor complex to produce a maximum functional response. This must be distinguished from the affinity, which is a measure of the ability of the drug to bind ...
of 40-60%, binding affinity of K
i=5-10nM and
EC50=50-90nM)
Agonists of full/unknown efficacy
*
Apomorphine (Apokyn – used to treat
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 ...
&
Restless leg 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 ...
) – biased at the D1 receptor.
*
Bromocriptine
Bromocriptine, originally marketed as Parlodel and subsequently under many brand names, is an ergoline derivative and dopamine agonist that is used in the treatment of pituitary tumors, Parkinson's disease, hyperprolactinaemia, neuroleptic malig ...
(Parlodel – used to treat
PD/
RLS)
*
Cabergoline
Cabergoline, sold under the brand name Dostinex among others, is a dopaminergic medication used in the treatment of high prolactin levels, prolactinomas, Parkinson's disease, and for other indications. It is taken by mouth.
Cabergoline is an ...
(Dostinex – used to treat PD/RLS)
*
Ciladopa (used to treat PD/RLS)
*
Dihydrexidine (used to treat PD/RLS)
*
Dinapsoline (used to treat PD/RLS)
*
Doxanthrine (used to treat PD/RLS)
*
Epicriptine (used to treat PD/RLS)
*
Lisuride (used to treat PD/RLS)
*
Pergolide
Pergolide, sold under the brand name Permax and Prascend (veterinary) among others, is an ergoline-based dopamine receptor agonist used in some countries for the treatment of Parkinson's disease. Parkinson's disease is associated with reduced do ...
(used to treat PD/RLS) – previously available as Permax, but removed from the market in the USA on March 29, 2007.
*
Piribedil (Pronoran and Trivastal – used to treat PD/RLS)
*
Pramipexole (Mirapex and Sifrol – used to treat PD/RLS)
*
Propylnorapomorphine (used to treat PD/RLS)
*
Quinagolide
Quinagolide (, ), sold under the brand name Norprolac, is a binding selectivity, selective dopamine receptor, dopamine D2 receptor, D2 receptor agonist which is used to manage hyperprolactinemia. It has also been found to be effective in the trea ...
(Norprolac – used to treat PD/RLS)
*
Ropinirole (Requip – used to treat PD/RLS)
*
Rotigotine (Neupro – used to treat PD/RLS)
*
Roxindole (used to treat PD/RLS)
*
Sumanirole (used to treat PD/RLS)
Some, such as
fenoldopam, are selective for
dopamine receptor D1
Dopamine receptor D1, also known as DRD1. It is one of the two types of D1-like receptor family receptors D1 and D5. It is a protein that in humans is encoded by the DRD1 gene.
Tissue distribution
D1 receptors are the most abundant kind of d ...
.
Related class of drugs: Indirect agonists
There are two
classes of drugs that act as
indirect agonist In pharmacology, an indirect agonist or indirect-acting agonist is a substance that enhances the release or action of an endogenous neurotransmitter but has no specific agonist activity at the neurotransmitter receptor itself. Indirect agonists work ...
s of dopamine receptors:
dopamine reuptake inhibitor
A dopamine reuptake inhibitor (DRI) is a class of drug which acts as a reuptake inhibitor of the monoamine neurotransmitter dopamine by blocking the action of the dopamine transporter (DAT). Reuptake inhibition is achieved when extracellular dop ...
s and
dopamine releasing agents. These are not considered dopamine agonists, since they have no specific agonist activity at dopamine
receptors
Receptor may refer to:
*Sensory receptor, in physiology, any neurite structure that, on receiving environmental stimuli, produces an informative nerve impulse
*Receptor (biochemistry), in biochemistry, a protein molecule that receives and responds ...
, but they are nonetheless related. Indirect agonists are prescribed for a wider range of conditions than standard dopamine agonists.
The most commonly prescribed indirect agonists of dopamine receptors include:
*
Amphetamine
Amphetamine (contracted from Alpha and beta carbon, alpha-methylphenethylamine, methylphenethylamine) is a central nervous system (CNS) stimulant that is used in the treatment of attention deficit hyperactivity disorder (ADHD), narcolepsy, an ...
and/or
dextroamphetamine
Dextroamphetamine (international nonproprietary name, INN: dexamfetamine) is a potent central nervous system (CNS) stimulant and enantiomer of amphetamine that is used in the treatment of attention deficit hyperactivity disorder (ADHD) and narc ...
(used to treat
ADHD
Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterised by symptoms of inattention, hyperactivity, impulsivity, and emotional dysregulation that are excessive and pervasive, impairing in multiple ...
,
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 ...
, and
obesity
Obesity is a medical condition, considered by multiple organizations to be a disease, in which excess Adipose tissue, body fat has accumulated to such an extent that it can potentially have negative effects on health. People are classifi ...
)
*
Bupropion
Bupropion, formerly called amfebutamone, and sold under the brand name Wellbutrin among others, is an atypical antidepressant that is indicated in the treatment of major depressive disorder, seasonal affective disorder, and to support smo ...
(used to facilitate
smoking cessation
Smoking cessation, usually called quitting smoking or stopping smoking, is the process of discontinuing tobacco smoking. Tobacco smoke contains nicotine, which is Addiction, addictive and can cause Substance dependence, dependence. As a resu ...
and treat
nicotine addiction and
clinical depression
Major depressive disorder (MDD), also known as clinical depression, is a mental disorder characterized by at least two weeks of pervasive low mood, low self-esteem, and loss of interest or pleasure in normally enjoyable activities. Intro ...
)
*
Lisdexamfetamine
Lisdexamfetamine, sold under the brand names Vyvanse and Elvanse among others, is a stimulant medication that is used as a treatment for attention deficit hyperactivity disorder (ADHD) in children and adults and for moderate-to-severe binge ...
(used to treat ADHD and
binge eating disorder
Binge eating disorder (BED) is an eating disorder characterized by frequent and recurrent binge eating episodes with associated negative psychological and social problems, but without the compensatory behaviors common to bulimia nervosa, OSFE ...
)
*
Methylphenidate
Methylphenidate, sold under the brand names Ritalin ( ) and Concerta ( ) among others, is a central nervous system (CNS) stimulant used in the treatment of attention deficit hyperactivity disorder (ADHD) and narcolepsy. It may be taken Oral adm ...
or
dexmethylphenidate
Dexmethylphenidate, sold under the brand name Focalin among others, is a central nervous system (CNS) stimulant used in the treatment of attention deficit hyperactivity disorder (ADHD) in those over the age of five years. It is taken by mouth. ...
(used to treat ADHD 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 ...
)
*
Modafinil
Modafinil, sold under the brand name Provigil among others, is a central nervous system (CNS) stimulant and wakefulness-promoting agent, eugeroic (wakefulness promoter) medication used primarily to treat narcolepsy, a sleep disorder characteri ...
or
armodafinil
Armodafinil, sold under the brand name Nuvigil, is a wakefulness-promoting medication which is used to treat excessive daytime sleepiness associated with obstructive sleep apnea, narcolepsy, and shift work disorder. It is also used off-label ...
(used primarily to treat
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 ...
)
Other examples include:
*
Cathinone
Cathinone (; also known as β-ketoamphetamine) is a monoamine alkaloid found in the shrub ''Catha edulis'' (khat) and is chemically similar to ephedrine, cathine, methcathinone and other amphetamines. It is probably the main contributor to t ...
*
Caffeine
Caffeine is a central nervous system (CNS) stimulant of the methylxanthine chemical classification, class and is the most commonly consumed Psychoactive drug, psychoactive substance globally. It is mainly used for its eugeroic (wakefulness pr ...
*
Cocaine
Cocaine is a tropane alkaloid and central nervous system stimulant, derived primarily from the leaves of two South American coca plants, ''Erythroxylum coca'' and ''Erythroxylum novogranatense, E. novogranatense'', which are cultivated a ...
(
anesthetic
An anesthetic (American English) or anaesthetic (British English; see spelling differences) is a drug used to induce anesthesia — in other words, to result in a temporary loss of sensation or awareness. They may be divided into t ...
with no medical uses as a
central nervous system stimulant)
*
Methamphetamine
Methamphetamine (contracted from ) is a potent central nervous system (CNS) stimulant that is mainly used as a recreational drug use, recreational or Performance-enhancing substance, performance-enhancing drug and less commonly as a secon ...
(used in rare circumstances to treat ADHD and
obesity
Obesity is a medical condition, considered by multiple organizations to be a disease, in which excess Adipose tissue, body fat has accumulated to such an extent that it can potentially have negative effects on health. People are classifi ...
)
*
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 ...
(endogenous
trace amine
Trace amines are an endogenous group of trace amine-associated receptor 1 (TAAR1) agonists – and hence, monoaminergic neuromodulators – that are structurally and metabolically related to classical monoamine neurotransmitters. Compared to ...
)
*
''p''-Tyramine (endogenous
trace amine
Trace amines are an endogenous group of trace amine-associated receptor 1 (TAAR1) agonists – and hence, monoaminergic neuromodulators – that are structurally and metabolically related to classical monoamine neurotransmitters. Compared to ...
)
History
Since the late 1960
Levodopa
Levodopa, also known as L-DOPA and sold under many brand names, is a dopaminergic medication which is used in the treatment of Parkinson's disease (PD) and certain other conditions like dopamine-responsive dystonia and restless legs syndrome. ...
(L-DOPA) has been used to treat
Parkinson's
Parkinson's disease (PD), or simply Parkinson's, is a neurodegenerative disease primarily of the central nervous system, affecting both motor and non-motor systems. Symptoms typically develop gradually and non-motor issues become more prevalen ...
disease but there has always been a debate whether the treatment is worth the
side effects
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 used ...
. Around 1970 clinicians started using the dopamine agonist
apomorphine alongside
L-DOPA
-DOPA, also known as -3,4-dihydroxyphenylalanine and used medically as levodopa, is made and used as part of the normal biology of some plants and animals, including humans. Humans, as well as a portion of the other animals that utilize -DO ...
to minimize the side effects caused by L-DOPA, the dopamine agonists bind to the dopamine receptor in the absence of dopamine. Apomorphine had limited use since it had considerable side effects and difficulty with administration. In 1974
bromocriptine
Bromocriptine, originally marketed as Parlodel and subsequently under many brand names, is an ergoline derivative and dopamine agonist that is used in the treatment of pituitary tumors, Parkinson's disease, hyperprolactinaemia, neuroleptic malig ...
was use widely after clinicians discovered its benefits in treating
Parkinsons. When using the two
drug
A drug is any chemical substance other than a nutrient or an essential dietary ingredient, which, when administered to a living organism, produces a biological effect. Consumption of drugs can be via insufflation (medicine), inhalation, drug i ...
classes together there is a possibility to reduce the amount of
L-DOPA
-DOPA, also known as -3,4-dihydroxyphenylalanine and used medically as levodopa, is made and used as part of the normal biology of some plants and animals, including humans. Humans, as well as a portion of the other animals that utilize -DO ...
by 20-30% and thus keeping the fluctuating motor responses to a minimum.
Dopamine agonists are often used in younger people as
monotherapy and as initial therapy instead of L-DOPA.
Although it is important to know that there is a correlation between the two drugs, if l-DOPA doesn't work dopamine agonists are also ineffective.
The early dopamine agonists, such as bromocriptine, were ergot derived and activated the D
2-receptor.
They induced major side effects such as fibrosis of cardiac valves. It is considered that the reason they induced such side effects is that they activate many types of receptors.
Due to the major adverse effects of ergot-derived dopamine agonists, they are generally not used in modern medicine and have mostly been abandoned in favor of non-ergot agonists such as
pramipexole,
ropinirole and
rotigotine. They do not induce as serious side effects although common side effects are
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 ...
,
edema
Edema (American English), also spelled oedema (British English), and also known as fluid retention, swelling, dropsy and hydropsy, is the build-up of fluid in the body's tissue (biology), tissue. Most commonly, the legs or arms are affected. S ...
and
hypotension
Hypotension, also known as low blood pressure, is a cardiovascular condition characterized by abnormally reduced blood pressure. Blood pressure is the force of blood pushing against the walls of the arteries as the heart pumps out blood and is ...
. Patients have also shown impaired impulse control such as
overspending
Overspending is spending more money than one can afford. It is a common problem when easy credit is available. The term overspending is also used for investment projects when payments exceed actual calculated cost.
Causes
Some overspending is a f ...
,
hypersexuality
Hypersexuality is a proposed medical condition said to cause unwanted or excessive sexual arousal, causing people to engage in or think about sexual activity to a point of distress or impairment., according to the website of ''Psychology Toda ...
and
gambling
Gambling (also known as betting or gaming) is the wagering of something of Value (economics), value ("the stakes") on a Event (probability theory), random event with the intent of winning something else of value, where instances of strategy (ga ...
.
See also
*
Dopamine antagonist
A dopamine antagonist, also known as an anti-dopaminergic and a dopamine receptor antagonist (DRA), is a type of drug which blocks dopamine receptors by receptor antagonism. Most antipsychotics are dopamine antagonists, and have been used in t ...
*
Dopamine reuptake inhibitor
A dopamine reuptake inhibitor (DRI) is a class of drug which acts as a reuptake inhibitor of the monoamine neurotransmitter dopamine by blocking the action of the dopamine transporter (DAT). Reuptake inhibition is achieved when extracellular dop ...
* Receptor
agonist
An agonist is a chemical that activates a Receptor (biochemistry), receptor to produce a biological response. Receptors are Cell (biology), cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an R ...
*
GABA receptor agonist
A GABA receptor agonist is a drug that is an agonist for one or more of the GABA receptors, producing typically sedative effects, and may also cause other effects such as anxiolytic, anticonvulsant, and muscle relaxant effects. There are three r ...
*
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 ...
*
Serotonin agonist
A serotonin receptor agonist is an agonist of one or more serotonin receptors. They activate serotonin receptors in a manner similar to that of serotonin (5-hydroxytryptamine; 5-HT), a neurotransmitter and hormone and the endogenous ligand of t ...
*
Adrenergic agonist (
sympathomimetic)
*
Parasympathomimetic drug
A parasympathomimetic drug, sometimes called a cholinomimetic drug or cholinergic receptor stimulating agent, is a substance that stimulates the parasympathetic nervous system (PSNS). These chemicals are also called cholinergic drugs becaus ...
(acetylcholine agonist)
*
Histamine agonist
References
Further reading
*
External links
*
{{Euphoriants