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

ergoline Ergoline is a chemical compound whose structural skeleton is contained in a variety of alkaloids, referred to as ergoline derivatives or ergoline alkaloids. Ergoline alkaloids, one being ergine, were initially characterized in ergot. Some of thes ...

-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 ag ...

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 beco ...

. 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 80% o ...

activity in the

substantia nigra The substantia nigra (SN) is a basal ganglia structure located in the midbrain that plays an important role in reward and movement. ''Substantia nigra'' is Latin for "black substance", reflecting the fact that parts of the substantia nigra ap ...

of the

brain A brain is an organ (biology), organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It is located in the head, usually close to the sensory organs for senses such as Visual perception, vision. I ...

. 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 In 2007, pergolide was withdrawn from the U.S. market for human use after several published studies revealed a link between the drug and increased rates of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 Pituitary pars intermedia dysfunction (PPID), or equine Cushing's disease, is an endocrine disease affecting the pituitary gland of horses. It is most commonly seen in older animals, and is classically associated with the formation of a long, wavy c ...

(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 C.H. Boehringer Sohn AG & Co. is the parent company of the Boehringer Ingelheim group, which was founded in 1885 by Albert Boehringer in Ingelheim am Rhein, Germany. As of 2018, Boehringer Ingelheim is one of the world's largest pharmaceutical ...

, 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 ...

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

Pharmacology

Pharmacodynamics

Pergolide acts as an agonist of

D₂ and D₁ and

serotonin Serotonin () or 5-hydroxytryptamine (5-HT) is a monoamine neurotransmitter. Its biological function is complex and multifaceted, modulating mood, cognition, reward, learning, memory, and numerous physiological processes such as vomiting and va ...

5-HT_1A, 5-HT_1B, 5-HT_2A, 5-HT_2B, and 5-HT_2C

receptor Receptor may refer to: *Sensory receptor, in physiology, any structure which, on receiving environmental stimuli, produces an informative nerve impulse *Receptor (biochemistry), in biochemistry, a protein molecule that receives and responds to a n ...

s. 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 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 Ergotamine, sold under the brand names Cafergot (with caffeine) and Ergomar among others, is an ergopeptine and part of the ergot family of alkaloids; it is structurally and biochemically closely related to ergoline. It possesses structural sim ...

, methysergide,

fenfluramine Fenfluramine, sold under the brand name Fintepla, is a serotonergic medication used for the treatment of seizures associated with Dravet syndrome and Lennox–Gastaut syndrome.https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/212102s003l ...

, and other serotonin 5-HT_2B agonists, including serotonin itself when elevated in the blood in

carcinoid syndrome Carcinoid syndrome is a paraneoplastic syndrome comprising the signs and symptoms that occur secondary to carcinoid tumors. The syndrome includes flushing and diarrhea, and less frequently, heart failure, vomiting and bronchoconstriction. It ...

. Pergolide can rarely cause

Raynaud's phenomenon Raynaud syndrome, also known as Raynaud's phenomenon, eponymously named after the physician Auguste Gabriel Maurice Raynaud, who first described it in his doctoral thesis in 1862, is a medical condition in which the spasm of small arteries cau ...

. 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