Pergolide
Encyclopedia
Pergolide is an ergoline
-based dopamine receptor
agonist
used in some countries for the treatment
of Parkinson's disease
.
Parkinson's disease is associated with low levels of the neurotransmitter
dopamine
in the brain. Pergolide has some of the same effects as dopamine in the body.
In 2007, pergolide was withdrawn from the U.S. market for human use, after several published studies revealed a link between the drug and increased rates of valvular dysfunction.[11]
However Pergolide is allowed for veterinary use to treat Cushings Syndrome in horses.
Furthermore, pergolide may also be used for veterinary purposes. It is commonly used for the treatment of pituitary pars intermedia
hyperplasia or Equine Cushing's Syndrome
(ECS) in horses.
, D1
and serotonin 5-HT1A, 5-HT1B, 5-HT2A, 5-HT2B, and 5-HT2C receptor
s. It may possess agonist activity at other dopamine receptor subtypes as well, similar to cabergoline. The weak agonist activity of pergolide at D1
receptors somewhat alters its clinical and side effect profile in the treatment of Parkinson's disease.
. In 2007, The United States Food and Drug Administration
announced a voluntary withdrawal of the drug by manufacturers due to the possibility of heart valve damage. Pergolide is not currently available in the United States. This problem is thought to be due to pergolide's action at the 5-HT2B serotonin receptors of cardiac myocytes, causing proliferative valve disease by the same mechanism as ergotamine, methysergide
, fenfluramine
, and other serotonin 5-HT2B agonists, including serotonin itself when elevated in the blood in carcinoid syndrome
. Pergolide can rarely cause Raynaud's phenomenon
. Among similar antiparkinsonian drugs, cabergoline
but not lisuride
exhibit this same type of serotonin receptor binding. In January, 2007, cabergoline
(Dostinex) was reported also to be associated with valvular proliferation heart damage. In March 2007, pergolide was withdrawn from the U.S. market for human use, due to serious valvular damage that was shown in two independent studies.
Pergolide has also been shown to impair associative learning.
At least one British Pergolide user has attracted some media attention with claims that it has caused him to develop a gambling addiction. In June 2010, it was reported that more than 100 Australian users of the drug are suing the manufacturer over both gambling and sex addiction problems they claim are the result of the drug's side effects.
On March 30, 2007, manufacturers of Pergolide agreed to withdraw the drug from the U.S. market after several published studies revealed a link between the drug and increased rates of valvular dysfunction.
However, Pergolide is still available in many other countries.
Ergoline
Ergoline is a chemical compound whose structural skeleton is contained in a diverse range of alkaloids including a few psychedelic drugs . Ergoline derivatives are used clinically for the purpose of vasoconstriction and in the treatment of migraines and Parkinson's disease...
-based dopamine receptor
Dopamine receptor
Dopamine receptors are a class of metabotropic G protein-coupled receptors that are prominent in the vertebrate central nervous system . The neurotransmitter dopamine is the primary endogenous ligand for dopamine receptors....
agonist
Agonist
An agonist is a chemical that binds to a receptor of a cell and triggers a response by that cell. Agonists often mimic the action of a naturally occurring substance...
used in some countries for the treatment
Therapy
This is a list of types of therapy .* Adventure therapy* Animal-assisted therapy* Aquatic therapy* Aromatherapy* Art and dementia* Art therapy* Authentic Movement* Behavioral therapy* Bibliotherapy* Buteyko Method* Chemotherapy...
of Parkinson's disease
Parkinson's disease
Parkinson's disease is a degenerative disorder of the central nervous system...
.
Parkinson's disease is associated with low levels of the neurotransmitter
Neurotransmitter
Neurotransmitters are endogenous chemicals that transmit signals from a neuron to a target cell across a synapse. Neurotransmitters are packaged into synaptic vesicles clustered beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they bind to...
dopamine
Dopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...
in the brain. Pergolide has some of the same effects as dopamine in the body.
In 2007, pergolide was withdrawn from the U.S. market for human use, after several published studies revealed a link between the drug and increased rates of valvular dysfunction.[11]
However Pergolide is allowed for veterinary use to treat Cushings Syndrome in horses.
Indications
Pergolide is not available in the United States, however it is still used in various other countries, where it is used to treat various conditions including Parkinson's disease, hyperprolactinemia, and restless leg syndrome.Furthermore, pergolide may also be used for veterinary purposes. It is commonly used for the treatment of pituitary pars intermedia
Pars intermedia
Pars intermedia is the boundary between the anterior and posterior lobes of the pituitary. It contains three types of cells - basophils, chromophobes, and colloid-filled cysts. The cysts are the remainder of Rathke’s pouch....
hyperplasia or Equine Cushing's Syndrome
Cushing's syndrome
Cushing's syndrome is a hormone disorder caused by high levels of cortisol in the blood. This can be caused by taking glucocorticoid drugs, or by tumors that produce cortisol or adrenocorticotropic hormone or CRH...
(ECS) in horses.
Pharmacology
Pergolide functions as an agonist at the dopamine D2Dopamine receptor D2
Dopamine receptor D2, also known as D2R, is a protein that, in humans, is encoded by the DRD2 gene.- Function :This gene encodes the D2 subtype of the dopamine receptor. This G protein-coupled receptor inhibits adenylyl cyclase activity...
, D1
Dopamine receptor D1
Dopamine receptor D1, also known as DRD1, is a protein that in humans is encoded by the DRD1 gene.- Function :This gene encodes the D1 subtype of the dopamine receptor. The D1 subtype is the most abundant dopamine receptor in the central nervous system. This G-protein-coupled receptor stimulates...
and serotonin 5-HT1A, 5-HT1B, 5-HT2A, 5-HT2B, and 5-HT2C receptor
Receptor (biochemistry)
In biochemistry, a receptor is a molecule found on the surface of a cell, which receives specific chemical signals from neighbouring cells or the wider environment within an organism...
s. It may possess agonist activity at other dopamine receptor subtypes as well, similar to cabergoline. The weak agonist activity of pergolide at D1
Dopamine receptor D1
Dopamine receptor D1, also known as DRD1, is a protein that in humans is encoded by the DRD1 gene.- Function :This gene encodes the D1 subtype of the dopamine receptor. The D1 subtype is the most abundant dopamine receptor in the central nervous system. This G-protein-coupled receptor stimulates...
receptors somewhat alters its clinical and side effect profile in the treatment of Parkinson's disease.
Side Effects
The drug is in decreasing use, as it was reported in 2003 to be associated with a form of heart disease called cardiac fibrosisCardiac fibrosis
Cardiac fibrosis refers to an abnormal thickening of the heart valves due to inappropriate proliferation of cardiac fibroblasts.Fibrocyte cells normally secrete collagen, and function to provide structural support for the heart...
. In 2007, The United States Food and Drug Administration
Food and Drug Administration
The Food and Drug Administration is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments...
announced a voluntary withdrawal of the drug by manufacturers due to the possibility of heart valve damage. Pergolide is not currently available in the United States. This problem is thought to be due to pergolide's action at the 5-HT2B serotonin receptors of cardiac myocytes, causing proliferative valve disease by the same mechanism as ergotamine, methysergide
Methysergide
Methysergide is a prescription drug used for prophylaxis of migraine headaches and is sold under the brand names Sansert and Deseril in 2 mg dosages.-Pharmacology:Methysergide interacts with serotonin receptors...
, fenfluramine
Fenfluramine
Fenfluramine is a drug that was part of the Fen-Phen anti-obesity medication . Fenfluramine was introduced on the U.S. market in 1973. It is the racemic mixture of two enantiomers, dextrofenfluramine and levofenfluramine...
, and other serotonin 5-HT2B agonists, including serotonin itself when elevated in the blood in carcinoid syndrome
Carcinoid syndrome
Carcinoid syndrome refers to the array of symptoms that occur secondary to carcinoid tumors. The syndrome includes flushing and diarrhea, and, less frequently, heart failure and bronchoconstriction...
. Pergolide can rarely cause Raynaud's phenomenon
Raynaud's phenomenon
In medicine, Raynaud's phenomenon is a vasospastic disorder causing discoloration of the fingers, toes, and occasionally other areas. This condition can also cause nails to become brittle with longitudinal ridges. Named for French physician Maurice Raynaud , the phenomenon is believed to be the...
. Among similar antiparkinsonian drugs, cabergoline
Cabergoline
Cabergoline , an ergot derivative, is a potent dopamine receptor agonist on D2 receptors. In vitro, rat studies show cabergoline has a direct inhibitory effect on pituitary lactotroph cells...
but not lisuride
Lisuride
Lisuride is an antiparkinson agent of the iso-ergoline class, chemically related to the dopaminergic ergoline Parkinson's drugs. Lisuride is described as free base and as hydrogen maleate salt.Lisuride is used to lower prolactin and, in low doses, to prevent migraine attacks...
exhibit this same type of serotonin receptor binding. In January, 2007, cabergoline
Cabergoline
Cabergoline , an ergot derivative, is a potent dopamine receptor agonist on D2 receptors. In vitro, rat studies show cabergoline has a direct inhibitory effect on pituitary lactotroph cells...
(Dostinex) was reported also to be associated with valvular proliferation heart damage. In March 2007, pergolide was withdrawn from the U.S. market for human use, due to serious valvular damage that was shown in two independent studies.
Pergolide has also been shown to impair associative learning.
At least one British Pergolide user has attracted some media attention with claims that it has caused him to develop a gambling addiction. In June 2010, it was reported that more than 100 Australian users of the drug are suing the manufacturer over both gambling and sex addiction problems they claim are the result of the drug's side effects.
On March 30, 2007, manufacturers of Pergolide agreed to withdraw the drug from the U.S. market after several published studies revealed a link between the drug and increased rates of valvular dysfunction.
However, Pergolide is still available in many other countries.