Pergolide

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Pergolide
Clinical data
Trade namesPermax, Prascend (veterinary), others
Other names8β-[(Methylthio)methyl]-6-propylergoline
AHFS/Drugs.comMonograph
Pregnancy
category
  • B
Routes of
administration		Oral
ATC code
Legal status
Legal status
Pharmacokinetic data
Protein binding90%
MetabolismExtensively Hepatic
Elimination half-life27 hours
Identifiers
  • (6aR,9R,10aR)-9-(methylthiomethyl)-7-propyl-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline
JSmol)
  • [H][C@]12C[C@@H](CSC)CN(CCC)[C@]1([H])Cc3c[nH]c4cccc2c34
  • InChI=1S/C19H26N2S/c1-3-7-21-11-13(12-22-2)8-16-15-5-4-6-17-19(15)14(10-20-17)9-18(16)21/h4-6,10,13,16,18,20H,3,7-9,11-12H2,1-2H3/t13-,16-,18-/m1/s1 checkY
  • Key:YEHCICAEULNIGD-MZMPZRCHSA-N checkY
 ☒NcheckY (what is this?)  (verify)

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 activity 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It was patented in 1978[3] and approved for medical use in 1989.[4] In 2007, pergolide was withdrawn from the U.S. market for human use after several published studies revealed a link between the drug and increased rates of valvular heart disease.[5] However,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.[6]

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.[citation needed]

Pergolide is available for veterinary use. Under the trade name Prascend, manufactured by

Equine Cushing's Syndrome (ECS) in horses.[6]

Pharmacology

Pharmacodynamics

Pergolide acts as an agonist of

cardiac valvulopathy due to activation of 5-HT2B receptors.[11]

Activities of pergolide at various sites[12][13][14][15]
Site Affinity (Ki [nM]) Efficacy (Emax [%]) Action
D1
 339 ? ?
D2S
 32 112 Full agonist
D2L
 26 52 Partial agonist
D3
 5.5 71 Partial agonist
D4
 59 56 Partial agonist
D5
 33 ? ?
5-HT1A 1.9 63 Partial agonist
5-HT1B 282 90 Partial agonist
5-HT1D 13 86 Partial agonist
5-HT2A 8.3 103 Full agonist
5-HT2B 7.1 113 Full agonist
5-HT2C 295 87 Partial agonist
5-HT6 30 ? ?
5-HT7 1.0–18 ? ?
α1A
 1,047 ? ?
α1B
 692 ? ?
α1D
 295 ? ?
α2A
 50 31 Partial agonist
α2B
 32 70 Partial agonist
α2C
 68 16 Partial agonist
α2D
 692 ? ?
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).[12][15]

Side effects

The drug is in decreasing use, as it was reported in 2003 to be associated with a form of heart disease called

Raynaud's phenomenon. Among similar antiparkinsonian drugs, cabergoline, but not lisuride, exhibit this same type of serotonin receptor binding.[18] In January 2007, cabergoline (Dostinex) was also reported to be associated with valvular proliferation heart damage.[19] 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.[20]

Pergolide has also been shown to impair associative learning.[21]

Addictive behaviors

At least one British pergolide user has attracted some media attention with claims that it has caused him to develop a

sex addiction[24]
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.[25]

References

  1. FDA
    . Retrieved 22 Oct 2023.
  2. ^ Anvisa (2023-03-31). "RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial" [Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control] (in Brazilian Portuguese). Diário Oficial da União (published 2023-04-04). Archived from the original on 2023-08-03. Retrieved 2023-08-16.
  3. ^ US patent 4166182A, Edmund C. Kornfeld & Nicholas J. Bach, "6-n-propyl-8-methoxymethyl or methylmercaptomethylergolines and related compounds", published 1979-08-28, issued 1979-08-28, assigned to Eli Lilly and Co 
  4. ISBN 9783527607495
    .
  5. ^ "Pergolide (marketed as Permax)". FDA Public Health Advisory. Archived from the original on 2007-04-08. Retrieved 2019-12-16.{{cite web}}: CS1 maint: bot: original URL status unknown (link)
  6. ^ a b Forney B. "Pergolide for Veterinary Use".
  7. ^ "Prascend for Horses". Boehringer Ingelheim. Valley Vet Supply.
  8. PMID 20130535
    .
  9. S2CID 221752556
    .
  10. PMID 18703043
    .
  11. PMID 24361689
    .
  12. ^
    S2CID 6200455
    .
  13. S2CID 35238120
    .
  14. S2CID 19260572
    .
  15. ^ a b "PDSP Database - UNC". pdsp.unc.edu. Archived from the original on 13 April 2021. Retrieved 15 January 2022.
  16. ^ ADRAC (August 2004). "Cardiac valvulopathy with pergolide". Aust Adv Drug React Bull. 23 (4). Archived from the original on 2007-12-15.
  17. ^ "Pergolide (marketed as Permax)". Public Health Advisory.
  18. KiB
    )     Presentation. Retrieved on 2007-03-30.
  19. PMID 17202453
    .
  20. ^ "MedWatch - 2007 Safety Information Alerts. Permax (pergolide) and generic equivalents". U.S. Food and Drug Administration. March 29, 2007. Retrieved 2007-03-30.
  21. PMID 16880771
    .
  22. ^ "Drug 'caused' gambling addiction". BBC TV. 24 January 2008.
  23. ^ "Parkinson's Gambler". ITV.com. 5 February 2008.
  24. ^ "Parkinson's treatment linked to sex, gambling". The Age. 4 June 2010.
  25. ^ "Pergolide - Drugs.com". www.drugs.com. Archived from the original on 7 January 2014. Retrieved 15 January 2022.