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Pergolide

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Pergolide chemical structure
Pergolide


IUPAC name
CAS number
66104-22-1
ATC code

N04BC02

PubChem
47811
DrugBank
APRD00663
Chemical formula {{{chemical_formula}}}
Molecular weight 314.489 g/mol
Bioavailability
Metabolism Extensively hepatic
Elimination half-life 27 hours
Excretion {{{excretion}}}
Pregnancy category B
Legal status Withdrawn (U.S.)
Routes of administration Oral

Pergolide is an ergoline-based dopamine receptor agonist used 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.

UsesEdit

Pergolide is also used to treat the stiffness, tremors, spasms, and poor muscle control of Parkinson's disease, although it has also been used to treat discomfort or pain in the lower extremities that can only be relieved by moving the legs. Pergolide is often used in conjunction with other medicines in the treatment of Parkinson's disease.

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.[1]

Side effectsEdit

The drug is in decreasing use, as it was reported in 2003 to be associated with a form of heart disease called cardiac fibrosis.[2] 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.[3] In January, 2007, cabergoline (Dostinex) was reported also to be associated with valvular proliferation heart damage.[4] In March 2007, pergolide was withdrawn from the U.S. market due to serious valvular damage that was shown in two independent studies.[5]

Pergolide has also been shown to impair associative learning.[6]

On March 30th, 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.[7]

ReferencesEdit

  1. Barbara Forney, VMD. Pergolide For Veterinary Use.
  2. ADRAC (August 2004). Cardiac valvulopathy with pergolide. Aust Adv Drug React Bull 23 (4). Free full text from the Australian Therapeutic Goods Administration
  3. 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.
  4. 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.
  5. MedWatch - 2007 Safety Information Alerts. Permax (pergolide) and generic equivalents. U.S. Food and Drug Administration. URL accessed on 2007-03-30.
  6. Breitenstein C et al. (2006). Tonic dopaminergic stimulation impairs associative learning in healthy subjects. Neuropsychopharmacology 31 (11): 2552–64.
  7. Pergolide Withdrawn From US Market



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