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 therapy of Parkinson's disease. Parkinson's disease is associated with reduced dopamine synthesis in the substantia nigra of the brain. Pergolide acts on many of the same receptors as dopamine to increase receptor activity.
It was patented in 1978
Medical uses
Pergolide is no longer 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,
Pharmacology
Pharmacodynamics
Pergolide acts as an agonist of dopamine D
2 and D
1 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 D
2 receptor, it has high D
1 receptor affinity and is one of the most potent D
1 receptor agonists of the dopamine receptor agonists that are clinically available.
The agonist activity of pergolide at the D
1 receptor somewhat alters its clinical and side effect profile in the treatment of Parkinson's disease. Pergolide has been said to be
hallucinogenic due to activation of 5-HT
2A receptors.
However, other sources have stated that the drug is non-hallucinogenic.
It has been associated with cardiac valvulopathy due to activation of 5-HT
2B receptors.
+ |
| D1 | 6.47 ± 0.04 | ? | ? |
| D2S | 8.30 ± 0.08 | 112 | Full agonist |
| D2L | 7.59 ± 0.06 | 52 | Partial agonist |
| D3 | 0.9 | 71 | Partial agonist |
| D4 | 7.23 ± 0.09 | 56 | Partial agonist |
| D5 | 7.48 ± 0.21 | ? | ? |
| 5-HT1A | 8.72 ± 0.13 | 63 | Partial agonist |
| 5-HT1B | 6.55 ± 0.10 | 90 | Partial agonist |
| 5-HT1D | 7.88 ± 0.11 | 86 | Partial agonist |
| 5-HT2A | 8.08 ± 0.06 | 103 | Full agonist |
| 5-HT2B | 8.15 ± 0.04 | 113 | Full agonist |
| 5-HT2C | 6.53 ± 0.06 | 87 | Partial agonist |
| 5-HT6 | 30 | ? | ? |
| 5-HT7 | 1.0–18 | ? | ? |
| α1A | 5.98 ± 0.11 | ? | ? |
| α1B | 6.16 ± 0.08 | ? | ? |
| α1D | 6.53 ± 0.19 | ? | ? |
| α2A | 5.39 ± 0.29 | 31 | Partial agonist |
| α2B | 7.30 ± 0.09 | 70 | Partial agonist |
| α2C | 7.49 ± 0.8 | 16 | Partial agonist |
| α2D | 7.17 ± 0.01 | ? | ? |
| β1 | >10,000 | – | – |
| β2 | >10,000 | – | – |
| H1 | 1,698 | ? | ? |
| M1 | >10,000 | – | – |
| σ1 | >10,000 | – | – |
| σ2 | 923 | ? | ? |
Notes: All receptors are human except α2D-adrenergic, which is rat (no human counterpart), and 5-HT6, 5-HT7, σ1, and σ2, which are all rodent (rat or guinea pig). |
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 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, exhibit this same type of serotonin receptor binding.
[Jähnichen S, Horowski R, Pertz H. Presentation. Retrieved on 2007-03-30.] In January 2007,
cabergoline (Dostinex) was also reported 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.
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.
Society and culture
Brand names
Brand names of pergolide include Permax and Prascend (veterinary), among others.
Research
Pergolide has been studied in the treatment of social anxiety disorder in one small study but was found to be ineffective.
