Pergolide

Overview

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 treatment 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. WP

It was patented in 1978 and approved for medical use in 1989. In 2007, pergolide was withdrawn from the U.S. market for human use after several published studies revealed a link between the drug and increased rates of valvular heart disease. However, a veterinary form of pergolide, marketed under the trade name Prascend, is permitted for the treatment of pituitary pars intermedia dysfunction (PPID) also known as equine Cushing's syndrome (ECS) in horses.[1–4] WP

Uses, dosage and effects

Medical uses

Pergolide is no longer available for use by humans in the United States, however, it is still used in various other countries, such as in the EU, where it is only recommended for patients who cannot take other treatments.[5] WP⚠ Wikipedia itself has flagged this text: citation needed.

Pergolide has also been tested for use in treatment of restless leg syndrome and hyperprolactinemia.[6][7] WP

Pergolide is currently available for veterinary use. Under the trade name Prascend, manufactured by Boehringer Ingelheim, it is commonly used in horses for the treatment of pituitary hyperplasia at the pars intermedia, also known as Equine Cushing's Syndrome (ECS).[4][8] WP

Risks and side effects

Side effects

In 2003, pergolide was reported to be associated with a form of heart disease called cardiac fibrosis. In March 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. This damage 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. Among similar antiparkinsonian drugs, cabergoline, but not lisuride, exhibit this same type of serotonin receptor binding and, in January 2007, cabergoline (Dostinex) was also reported to be associated with valvular proliferation heart damage.[9–13] WP

Pergolide has also been shown to impair associative learning, and can rarely cause Raynaud's phenomenon.[14] WP

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.[15][16][17] WP

Pharmacology

Pharmacodynamics

Pergolide acts as an agonist of dopamine D₂ and 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. Although pergolide is more potent as an agonist of the D₂ receptor, it has high D₁ receptor affinity and is one of the most potent D₁ receptor agonists of the dopamine receptor agonists that are clinically available. The agonist activity of pergolide at the D₁ 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-HT2A receptors. However, other sources have stated that the drug is non-hallucinogenic. It has been associated with cardiac valvulopathy due to activation of 5-HT2B receptors.[18–22] WP⚠ A table follows this text in the source and is not copied here. Open the source to see it.

Research

Research

Pergolide has been studied in the treatment of social anxiety disorder in one small study but was found to be ineffective.[23][24] WP

Legal status

Brand names

Brand names of pergolide include Permax and Prascend (veterinary), among others.[25] WP

Chemistry

Formula

C19H26N2S PC

CAS number

66104-22-1 PC

Molar mass (g/mol)

314.5 PC

IUPAC name (computed by PubChem)

(6aR,9R,10aR)-9-(methylsulfanylmethyl)-7-propyl-6,6a,8,9,10,10a-hexahydro-4H-indolo[4,3-fg]quinoline PC

SMILES

CCCN1C[C@@H](C[C@H]2[C@H]1CC3=CNC4=CC=CC2=C34)CSC PC

InChIKey

YEHCICAEULNIGD-MZMPZRCHSA-N PC

PubChem CID

47811

Harm reduction information

No harm reduction data is on file for this compound yet. That means no dose, timing or combination data from PsychonautWiki or TripSit. Please don't guess a dose from similar compounds. If you have taken it and feel unwell, contact emergency services or a poison control center.

User reports

Pop culture

No references added yet.

Sources

1. Other 6-n-propyl-8-methoxymethyl or methylmercaptomethylergolines and related compounds
2. Other Fischer J, Ganellin CR. Analogue-based Drug Discovery. 2006
3. Journal / agency Pergolide (marketed as Permax)
4. Other Forney B. Pergolide for Veterinary Use
5. Journal / agency Ergot-derived dopamine agonists - referral | European Medicines Agency (EMA). 2008-06-26
6. Journal / agency Trenkwalder C, Hundemer HP, Lledo A, Swieca J, Polo O, Wetter TC, Ferini-Strambi L, de Groen H, Quail D, Brandenburg U. Efficacy of pergolide in treatment of restless legs syndrome: the PEARLS Study. Neurology. April 2004. doi:10.1212/01.WNL.0000124465.20878.84 · PMID 15111679
7. Journal / agency Kletzky OA, Borenstein R, Mileikowsky GN. Pergolide and bromocriptine for the treatment of patients with hyperprolactinemia. American Journal of Obstetrics and Gynecology. February 1986. doi:10.1016/0002-9378(86)90685-x · PMID 3080892
8. Other Prascend for Horses
9. Journal / agency ADRAC. Cardiac valvulopathy with pergolide. Aust Adv Drug React Bull. August 2004
10. Journal / agency Pergolide (marketed as Permax)
11. Journal / agency MedWatch - 2007 Safety Information Alerts. Permax (pergolide) and generic equivalents. March 29, 2007
12. Other "Pergolide and Cabergoline But not Lisuride Exhibit Agonist Efficacy at Serotonin 5-HT2B Receptors"
13. Journal / agency Schade R, Andersohn F, Suissa S, Haverkamp W, Garbe E. Dopamine agonists and the risk of cardiac-valve regurgitation. The New England Journal of Medicine. January 2007. doi:10.1056/NEJMoa062222 · PMID 17202453
14. Journal / agency Breitenstein C, Korsukewitz C, Flöel A, Kretzschmar T, Diederich K, Knecht S. Tonic dopaminergic stimulation impairs associative learning in healthy subjects. Neuropsychopharmacology. November 2006. doi:10.1038/sj.npp.1301167 · PMID 16880771
15. Other Drug 'caused' gambling addiction. 24 January 2008
16. Other Parkinson's Gambler. 5 February 2008
17. Other Hagan K. Parkinson's treatment linked to sex, gambling. 4 June 2010
18. Journal / agency McClure MM, Harvey PD, Goodman M, Triebwasser J, New A, Koenigsberg HW, Sprung LJ, Flory JD, Siever LJ. Pergolide treatment of cognitive deficits associated with schizotypal personality disorder: continued evidence of the importance of the dopamine system in the schizophrenia spectrum. Neuropsychopharmacology. May 2010. doi:10.1038/npp.2010.5 · PMID 20130535 · PMC3055340
19. Journal / agency Gillman PK. Triptans, serotonin agonists, and serotonin syndrome (serotonin toxicity): a review. Headache. February 2010. doi:10.1111/j.1526-4610.2009.01575.x · PMID 19925619
20. Journal / agency Cussac D, Boutet-Robinet E, Ailhaud MC, Newman-Tancredi A, Martel JC, Danty N, Rauly-Lestienne I. Agonist-directed trafficking of signalling at serotonin 5-HT2A, 5-HT2B and 5-HT2C-VSV receptors mediated Gq/11 activation and calcium mobilisation in CHO cells. European Journal of Pharmacology. October 2008. doi:10.1016/j.ejphar.2008.07.040 · PMID 18703043
21. Journal / agency Gumpper RH, Roth BL. Psychedelics: preclinical insights provide directions for future research. Neuropsychopharmacology. January 2024. doi:10.1038/s41386-023-01567-7 · PMID 36932180 · PMC10700551
22. Journal / agency Cavero I, Guillon JM. Safety Pharmacology assessment of drugs with biased 5-HT(2B) receptor agonism mediating cardiac valvulopathy. Journal of Pharmacological and Toxicological Methods. 2014. doi:10.1016/j.vascn.2013.12.004 · PMID 24361689
23. Journal / agency van Ameringen M, Mancini C, Farvolden P, Oakman J. Drugs in development for social anxiety disorder: more to social anxiety than meets the SSRI. Expert Opinion on Investigational Drugs. October 2000. doi:10.1517/13543784.9.10.2215 · PMID 11060802
24. Journal / agency Villarreal G, Johnson MR, Rubey R, Lydiard RB, Ballanger JC. Treatment of social phobia with the dopamine agonist pergolide. Depression and Anxiety. 2000. doi:10.1002/(sici)1520-6394(2000)11:1<45::aid-da8>3.0.co;2-8 · PMID 10723636
25. Other Pergolide

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