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20-September-2008 09:55:51 - Pergolide Pergolide Systematic IUPAC name 6aR,9R,10aR-9-methylthiomethyl-7-propyl- -4,6,6a,7,8,9,10,10a-octahydroindolo4,3-fgquinoline Identifiers CAS number 66104-22-1 ATC code N04BC02 PubChem 47811 DrugBank APRD00663 Chemical data Formula C19H26N2S Mol. mass 314.489 g/mol Pharmacokinetic data Bioavailability ? Protein binding 90% Metabolism Extensively hepatic Half life 27 hours Excretion ? Therapeutic considerations Pregnancy cat. B Legal status Withdrawn U.S. Routes Oral Pergolide is an ergoline-based dopamine receptor agonist used for the treatment of Parkinson's disease.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. Uses 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. Since Pergolide can reduce prolactin levels, it is often used to treat hyperprolactinemia. 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 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.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Dostinex was reported also to be associated with valvular proliferation heart damage.4 In March 2007, pergolide was withdrawn from the U.S. market due to serious valvular damage that was shown in two independent studies.5 Pergolide has also been shown to impair associative learning.6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 However, Pergolide is still available in many other countries including Canada. References ^ Barbara Forney, VMD. Pergolide For Veterinary Use. ^ ADRAC August 2004. Cardiac valvulopathy with pergolide. Aust Adv Drug React Bull 23 4. Free full text from the Australian Therapeutic Goods Administration ^ 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. ^ 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. ^ MedWatch - 2007 Safety Information Alerts. Permax pergolide and generic equivalents. U.S. Food and Drug Administration March 29, 2007. Retrieved on 2007-03-30. ^ 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. ^ Pergolide Withdrawn From US Market v d e Ergolines Lysergic acid derivatives Bromocriptine, Cabergoline, Ergine, Ergonovine, Ergotamine, Lysergic acid, Lysergol, LSD, D-Lysergic acid hydroxyethylamide, Lisuride, Methergine, Methysergide, Pergolide Hallucinogenic lysergamides AL-LAD, ALD-52, BU-LAD, CYP-LAD, DAL, DAM-57, Ergonovine, ETH-LAD, LAE-32, LSD, LPD-824, LSM-775, D-Lysergic acid N-α-hydroxyethylamide, Methylergonovine, MLD-41, PARGY-LAD, PRO-LAD Other ergolines Ergoline Natural sources Argyreia nervosa, Claviceps spp., Ipomoea tricolor, Ipomoea violacea, Rivea corymbosa v d e Anti-parkinson drugs: dopaminergic agents N04B Dopa and derivatives Droxidopa Levodopa Melevodopa Etilevodopa Adamantane derivatives Amantadine Dopamine agonists A-412,997 Apomorphine Bromocriptine Cabergoline Dihydrexidine Dihydroergocryptine mesylate Fenoldopam Lisuride Pergolide Piribedil Pramipexole Propylnorapomorphine Quinpirole Ropinirole Rotigotine SKF 38393 SKF 82958 MAOIs B Selegiline Rasagiline COMT inhibitors Entacapone Tolcapone Other Budipine dopa decarboxylase inhibitor Carbidopa Tablets This pharmacology-related article is a stub. Retrieved from http://en..org/wiki/Pergolide Categories: Dopamine agonists | Withdrawn drugs | Equine medications | Pharmacology stubs Views Article Discussion this page History Personal tools Log in / create account Navigation Main page Contents Featured content Current events Random article Search Go Search Interaction Community portal Recent changes Contact Donate to Help Toolbox What links here Related changes Upload file Special pages Printable version Permanent link Cite this page Languages Deutsch This page was last modified on 21 June 2008, at 14:27
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