Pergolide

Pergolide (Permax, Pergotoliderived) 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In 2007, pergolide was withdrawn from the U.S. market for human use, after several published studies revealed a link between the drug and increased rates of valvular dysfunction.[11]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.

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

Pharmacology
Pergolide functions as an agonist at the dopamine D2, D1 and serotonin 5-HT1A, 5-HT1B, 5-HT2A, 5-HT2B, and 5-HT2C receptors. 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.

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 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 In March 2007, pergolide was withdrawn from the U.S. market for human use, due to serious valvular damage that was shown in two independent studies.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.