Pergolide

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Pergolide
Pergolid Structural Formulae V.1.svg
Systematic (IUPAC) name
(8β)-8-[(methylthio)methyl]-6-propylergoline
Clinical data
AHFS/Drugs.com monograph
Pregnancy cat. B
Legal status Withdrawn (U.S.)
Routes Oral
Pharmacokinetic data
Protein binding 90%
Metabolism Extensively hepatic
Half-life 27 hours
Identifiers
CAS number 66104-22-1 YesY
ATC code N04BC02
PubChem CID 47811
IUPHAR ligand 48
DrugBank DB01186
ChemSpider 43503 YesY
UNII 24MJ822NZ9 YesY
KEGG D08339 YesY
ChEBI CHEBI:63617 YesY
ChEMBL CHEMBL531 YesY
Synonyms (6aR,9R,10aR)-9-(methylthiomethyl)-7-propyl-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline
Chemical data
Formula C19H26N2S 
Mol. mass 314.489 g/mol
 YesY (what is this?)  (verify)

Pergolide (trade name Permax) 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In 2007, pergolide was withdrawn from the U.S. market for human use, after several published studies revealed a link between the drug and increased rates of valvular heart disease.[1]

However, a veterinary form of pergolide (trade name Prascend) is permitted for the treatment of equine Cushing's syndrome (ECS) in horses.[2]

Indications[edit]

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.

Furthermore, pergolide may also be used for veterinary purposes. Under the trade name Prascend, manufactured by Boehringer Ingelheim,[3] it is commonly used for the treatment of pituitary pars intermedia hyperplasia or Equine Cushing's Syndrome (ECS) in horses.[4]

Pharmacology[edit]

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[edit]

The drug is in decreasing use, as it was reported in 2003 to be associated with a form of heart disease called cardiac fibrosis.[5] 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.[6] 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-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.[7] In January, 2007, cabergoline (Dostinex) was reported also to be associated with valvular proliferation heart damage.[8] 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.[9]

Pergolide has also been shown to impair associative learning.[10]

Claimed side effects[edit]

At least one British pergolide user has attracted some media attention with claims that it has caused him to develop a gambling addiction.[11][12] 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[13] problems they claim are the result of the drug's side effects.

References[edit]

  1. ^ FDA Public Health Advisory: Pergolide (marketed as Permax)
  2. ^ [1]
  3. ^ http://www.valleyvet.com/ct_detail.html?pgguid=e0f4888c-86de-4ce9-9013-6d947df697a8&gas=pergolide%20mesylate
  4. ^ Barbara Forney, VMD. "Pergolide For Veterinary Use". 
  5. ^ ADRAC (August 2004). "Cardiac valvulopathy with pergolide". Aust Adv Drug React Bull 23 (4).  Free full text from the Australian Therapeutic Goods Administration
  6. ^ Public Health Advisory - Pergolide (marketed as Permax)
  7. ^ Jähnichen S, Horowski R, Pertz H. "Pergolide and Cabergoline But not Lisuride Exhibit Agonist Efficacy at Serotonin 5-HT2B Receptors". PDF (515 KiB) Presentation. Retrieved on 2007-03-30.
  8. ^ Schade R, Andersohn F, Suissa S, Haverkamp W, Garbe E (2007). "Dopamine agonists and the risk of cardiac-valve regurgitation". N Engl J Med 356 (1): 29–38. doi:10.1056/NEJMoa062222. PMID 17202453. 
  9. ^ "MedWatch - 2007 Safety Information Alerts. Permax (pergolide) and generic equivalents". U.S. Food and Drug Administration. March 29, 2007. Retrieved 2007-03-30. 
  10. ^ Breitenstein C et al. (2006). "Tonic dopaminergic stimulation impairs associative learning in healthy subjects". Neuropsychopharmacology 31 (11): 2552–64. doi:10.1038/sj.npp.1301167. PMID 16880771. 
  11. ^ "Drug 'caused' gambling addiction" BBC TV 24 Jan. 2008
  12. ^ "Parkinson's Gambler" ITV.com 5 Feb. 2008
  13. ^ "Parkinson's treatment linked to sex, gambling" 'The Age' 4 June 2010