Pergolide, sold under the brand name Permax and Prascend (veterinary) among others, is an ergoline-based

dopamine receptor 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 diffe ...

agonist An agonist is a chemical that activates a receptor to produce a biological response. Receptors are cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an antagonist blocks the action of the ago ...

used in some countries for the treatment of

Parkinson's disease Parkinson's disease (PD), or simply Parkinson's, is a long-term degenerative disorder of the central nervous system that mainly affects the motor system. The symptoms usually emerge slowly, and as the disease worsens, non-motor symptoms becom ...

. Parkinson's disease is associated with reduced

dopamine Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic chemical of the catecholamine and phenethylamine families. Dopamine constitutes about 8 ...

activity in the substantia nigra of the

brain The brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It consists of nervous tissue and is typically located in the head ( cephalization), usually near organs for special ...

. Pergolide acts on many of the same receptors as dopamine to increase receptor activity. It was patented in 1978 and approved for medical use in 1989. In 2007, pergolide was withdrawn from the U.S. market for human use after several published studies revealed a link between the drug and increased rates of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 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). These ...

. However, a veterinary form of pergolide, marketed under the trade name Prascend, is permitted for the treatment of pituitary pars intermedia dysfunction (PPID) also known as equine Cushing's syndrome (ECS) in horses.

Medical uses

Pergolide is not available for use by humans 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. Pergolide is available for veterinary use. Under the trade name Prascend, manufactured by Boehringer Ingelheim, it is commonly used for the treatment of pituitary hyperplasia at the

pars intermedia Pars intermedia is the boundary between the anterior and posterior lobes of the pituitary. It contains colloid-filled cysts and two types of cells - basophils and chromophobes. The cysts are the remainder of Rathke’s pouch. In human fetal life ...

or Equine Cushing's Syndrome (ECS) in horses.

Pharmacology

Pharmacodynamics

Pergolide acts as an agonist of

D₂ and D₁ and serotonin 5-HT_1A, 5-HT_1B, 5-HT_2A, 5-HT_2B, and 5-HT_2C receptors. It may possess agonist activity at other dopamine receptor subtypes as well, similar to cabergoline. Although pergolide is more potent as an agonist of the D₂ receptor, it has high D₁ receptor affinity and is one of the most potent D₁ receptor agonists of the dopamine receptor agonists that are clinically available. The agonist activity of pergolide at the D₁ receptor somewhat alters its clinical and side effect profile in the treatment of Parkinson's disease. Pergolide is said to be

hallucinogenic Hallucinogens are a large, diverse class of psychoactive drugs that can produce altered states of consciousness characterized by major alterations in thought, mood, and perception as well as other changes. Most hallucinogens can be categorize ...

due to activation of 5-HT_2A receptors. It has been associated with cardiac valvulopathy due to activation of 5-HT_2B receptors.

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 fibrosis. In 2007, The United States

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...

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 for human use. This problem is thought to be due to pergolide's action at the 5-HT_2B serotonin receptors of cardiac myocytes, causing proliferative valve disease by the same mechanism as ergotamine, methysergide, fenfluramine, and other serotonin 5-HT_2B 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 Lisuride, sold under the brand name Dopergin among others, is a monoaminergic medication of the ergoline class which is used in the treatment of Parkinson's disease, migraine, and high prolactin levels. It is taken by mouth. Side effects of lis ...

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.

Addictive behaviors

At least one British pergolide user has attracted some media attention with claims that it has caused him to develop a

gambling addiction Problem gambling or ludomania is repetitive gambling behavior despite harm and negative consequences. Problem gambling may be diagnosed as a mental disorder according to ''DSM-5'' if certain diagnostic criteria are met. Pathological gambling is ...

. 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"Parkinson's treatment linked to sex, gambling" 'The Age' 4 June 2010
/ref> problems they claim are the result of the drug's side effects.

Society and culture

Brand names

Brand names of pergolide include Permax and Prascend (veterinary), among others.

References

{{Ergolines 5-HT2B agonists D2-receptor agonists D3 receptor agonists D4 receptor agonists Dopamine receptor modulators Equine medications Ergolines Prolactin inhibitors Thioethers Withdrawn drugs