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Pergolide

  • Withdrawn substance
  • Withdrawn
  • Identity checked
  • Sources last checked 2026-09-04

This page shows what was measured, who it was measured in, and what that does not settle.

What Pergolide does in the body

Pergolide stimulates the dopamine receptors that Parkinson's disease depletes, which improves movement.

It is built on an ergot skeleton, and ergot compounds also stimulate a serotonin receptor found on heart valve tissue. Stimulating that receptor tells valve cells to grow and stiffen, so the valve thickens and stops closing properly. The dopamine agonists that are not built on an ergot skeleton do the first thing and not the second.

Why people take it. Formerly added to levodopa treatment for Parkinson’s disease.

What happened in people

New heart-valve leakage was about seven times as likely among current pergolide users.

Reviewed first-read answer

Where this came from

A person wrote this and a reviewer approved it against this exact record. It carries no effect size.

A reviewer approved this against this record. The reviewed-claim record carrying the exact population and effect size does not exist yet.

No source is stored against this line.

The limit that matters most

The harm varied by valve and cannot be reduced to one class-wide risk number.

Where it acts
Striatal dopamine receptors; the toxicity site is the 5-HT2B receptor on cardiac valve fibroblasts
Kind of result
The kind of result is not recorded
Supervision
Professional supervision is normally required. A regulator classifies this substance in a way that restricts how it is supplied.

What the registries record it as

  • The substance registry classes this as chemical.

    FDA substance registry · 24MJ822NZ9 · read 2026-08-29

  • Its recorded molecular formula is C19H26N2S, weighing 314.5.

    PubChem record · 47811 · read 2026-08-29

Where each sentence above came from

A person wrote this explanation into the record, with the studies named in the path below.

A reviewer approved this sentence against this exact record and its sources.

The limit a reviewer approved as the one that matters most here.

The four opening statements run to 90 words.

Words this page uses

Four words worth knowing first

Chosen from what this page shows, with each one explained before the word it depends on.

Absolute difference

An absolute difference is how many more people in a hundred were affected.

A picture of it, and where the picture fails

It is like counting heads in two rooms of a hundred.

Where that stops being true. Heads are easy to count. Study results carry a margin of error too.

What people get wrong. It is confused with a percentage change, which can look far larger.

The arithmetic difference in event rates between arms.

Confidence interval

A confidence interval is the range the true answer is likely to sit in.

A picture of it, and where the picture fails

It is like a weather forecast giving a range rather than one number.

Where that stops being true. A forecast range covers tomorrow. This one covers what the study could resolve.

What people get wrong. The middle number is read as the answer. A range crossing zero means no change is still possible.

An interval estimate that would contain the true parameter in a stated proportion of repeated studies.

What happened in peopleRead from sources, not yet reviewed

What happened in people

Each card is one study: the exact question it asked, who was in it, and whether it showed what it set out to show.

Incidence-rate ratio for newly diagnosed cardiac-valve regurgitation with current use of individual dopamine agonists, 1988 to 2005

The study showed what it set out to show

Who was studied
UK General Practice Research Database nested case-control (Schade et al.)
How many people
11417
Study design
Population-based cohort with nested case-control analysis
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
Pergolide incidence-rate ratio 7.1 (95% CI 2.3 to 22.3); cabergoline 4.9 (1.5 to 15.6); no increase with other dopamine agonists
Repeated elsewhere
Replicated

What this does not prove. Meeting one endpoint in one population does not carry to other goals or other people.

The limits of this study, and where it came from

Main limit. Only 31 case patients were identified across the whole cohort, so the confidence intervals are wide and the analysis detects clinically diagnosed regurgitation rather than subclinical disease.

How far it carries. This study is recorded from the curated record, not from the registry match.

Form and route. Oral tablet, three times daily, titrated over weeks

Interval reported. 95% CI 2

Written into the record, not signed off as a reviewed claim.

Prevalence of grade 3 to 4 valve regurgitation on echocardiography in patients on pergolide, cabergoline or non-ergot agonists versus controls

The study showed what it set out to show

Who was studied
Echocardiographic prevalence study (Zanettini et al.)
How many people
245
Study design
Cross-sectional echocardiographic prevalence study with controls
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
23.4% on pergolide and 28.6% on cabergoline versus 0% on non-ergot agonists and 5.6% in controls; mitral relative risk 6.3, P = 0.008; aortic 4.2, P = 0.01
Repeated elsewhere
Replicated

What this does not prove. Meeting one endpoint in one population does not carry to other goals or other people.

The limits of this study, and where it came from

Main limit. Tricuspid estimates did not reach significance in either ergot group (P = 0.16 and P = 0.12) on 64 and 49 patients, so those figures are uninformative rather than negative.

How far it carries. This study is recorded from the curated record, not from the registry match.

Form and route. Oral tablet, three times daily, titrated over weeks

Interval reported. Not recorded in this summary

Written into the record, not signed off as a reviewed claim.

What we know
RNAWiki holds 2 written-up human studies for this substance, each with the question it asked.
How we know it
Each card names the study, the number of people and what the study set out to measure.
What this does not prove
These summaries were written by a person and have not been signed off as reviewed claims.
Why it matters
A study that failed is as informative as one that worked, and both are here.
What we still do not know
No reviewed claim exists, so no exact population, effect size or interval is published yet.

What it changes in the bodyRead from sources, not yet reviewed

The path through the body

From what a person takes to what changes. A solid line is a step measured in people. A dashed line is a step nobody has measured that way.

  1. Start

    Pergolide

    What a person takes: Oral tablet, three times daily, titrated over weeks.

    The measurement behind this step

    Oral ergoline given as an adjunct to levodopa and carbidopa, titrated slowly from a low starting dose to limit nausea and orthostatic hypotension. Plasma half-life around 27 hours with extensive hepatic metabolism.

  2. Getting in

    An oral tablet, titrated slowly upward

    Taken by mouth several times a day, with the dose built up gradually alongside levodopa.

    Measured in people. Written by a person from the study named beside the step. Not signed off as a reviewed claim.

    The measurement behind this step
  3. Reaching the cell

    Crosses into the brain and reaches the striatum

    It enters brain tissue and reaches the region whose dopamine-producing cells are dying in Parkinson's disease.

    Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.

    The measurement behind this step

    Lipophilic ergoline with good central nervous system penetration, reaching postsynaptic dopamine receptors in the striatum. It also circulates to cardiac valve tissue, which has no barrier equivalent.

  4. What it acts on

    Agonist at dopamine D1 and D2 — and at 5-HT2B

    It switches on the dopamine receptors that improve movement. The ergot skeleton also switches on a serotonin receptor found on heart valve cells.

    Measured in people. Written by a person from the study named beside the step. Not signed off as a reviewed claim.

    The measurement behind this step

    Direct agonism at dopamine D1 and D2 receptors substitutes for lost endogenous dopaminergic tone. The ergoline scaffold confers agonism at 5-HT2B, a Gq-coupled receptor expressed on cardiac valve interstitial cells and largely absent from adult myocardium.

  5. The change it makes

    Motor symptoms improve; valve leaflets thicken and stiffen

    Movement gets better. Meanwhile, valve tissue is being told to grow, so leaflets thicken, stiffen and stop meeting properly, and blood leaks backwards.

    Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.

    The measurement behind this step

    Striatal dopamine receptor stimulation reduces off time and motor fluctuation. At the valve, 5-HT2B-driven mitogenesis and TGF-beta signalling in interstitial cells cause plaque-like leaflet thickening and apical displacement of coaptation, measurable as increased mitral tenting area with a linear relationship to regurgitation severity.

  6. What that does for a person

    Parkinson symptoms controlled; a quarter of patients develop significant valve leak

    The drug worked for Parkinson's disease. On echocardiography, 23.4% of patients had moderate or severe valve leakage against 5.6% of controls and none on the non-ergot alternatives.

    Measured in people. Written by a person from the study named beside the step. Not signed off as a reviewed claim.

    The measurement behind this step

    Measured endpoints: clinically important regurgitation in 23.4% on pergolide versus 5.6% of controls and 0% on non-ergot agonists; incidence-rate ratio 7.1 (95% CI 2.3 to 22.3) for newly diagnosed regurgitation in an 11,417-patient cohort.

No suggested links are held for this record, so nothing is hidden from this path.

What we know
The record describes 5 steps from taking it to an effect in a person.
How we know it
Each step names the study behind it in the technical detail beside it.
What this does not prove
A change inside the body is a reason to look. It is not a result in a person.
Why it matters
A reader can see exactly where the chain stops being measured in people.
What we still do not know
No reviewed claim binds any of these steps to a named population.

What is missing or unclearRead from sources, not yet reviewed

Were people like you studied?

RNAWiki cannot tell whether a study fits you. It can show who was in it, and where the result stops carrying.

Who was studied

People similar to this profile were included.

  • No human patient in the United States. Pergolide remains widely used in veterinary medicine for equine pituitary pars intermedia dysfunction, where the risk calculus differs.

Who is missing from the studies

  • Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.

Where the result stopped carrying

  • Marketed from 1988 and withdrawn in March 2007, nineteen years later, for a mechanism the ergot literature had described since the 1960s
  • Codified in the FDA withdrawn-for-safety list at 81 FR 69668 as "all drug products containing pergolide mesylate"
  • This is a scope explorer, not a diagnosis engine.
  • It shows who was studied so you can see whether people similar to you were included.

RNAWiki cannot tell whether a study fits you. It can show who was in it.

What it would be like to takeRead from sources, not yet reviewed

Why it might seem to do nothing

A real effect and a noticed effect are different things. These are the recorded reasons the two come apart.

It was studied in different people

The people in the studies were not much like the reader.

On this record: Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.

The evidence may simply be wrong

Small early studies often do not hold up.

On this record: RNAWiki has not yet published a reviewed conclusion for this use.

Other reasons RNAWiki checked and found nothing for (11)
It was studied for a different goal
The studies measured something else entirely. Nothing in this record points to this reason.
A different form was studied
The studied form is not the form on the shelf. Nothing in this record points to this reason.
There was nothing to correct
Where a level is already normal, topping it up may change nothing. Nothing in this record points to this reason.
Something else had to happen too
In the studies it was paired with training, a diet or another treatment. Nothing in this record points to this reason.
The change is too small to feel
A real change can still sit below what a person notices. Nothing in this record points to this reason.
Day-to-day swing hides it
Sleep, food, stress and time of day move most numbers more than this would. Nothing in this record points to this reason.
Not enough time yet
The studies ran longer than the person has waited. Nothing in this record points to this reason.
It was not taken as studied
Missed days change the result, and studies count them. Nothing in this record points to this reason.
Something else changed at the same time
Two changes at once cannot be told apart afterwards. Nothing in this record points to this reason.
The product may not be what it says
Contents of a sold product are not always what the label states. Nothing in this record points to this reason.
No recorded reason
RNAWiki has nothing stored that would explain it. Nothing in this record points to this reason.

None of these is a reason to take more. Taking more is not a step this page ever suggests.

What it would be like to takeRead from sources, not yet reviewed

What taking it involves

The recorded facts about getting hold of it and using it. Nothing here is a suggestion about what you should do.

How it is supplied

Withdrawn

Quoted from a source

Where this came from

Copied from a source RNAWiki stored, with the source named.

Read from the recorded approval status.

No source is stored against this line.

Form and route

Oral tablet, three times daily, titrated over weeks

Source-linked record

Where this came from

A person wrote this into the record with the study named beside it. No reviewer has signed it off.

The form and route recorded on this substance.

No source is stored against this line.

Who oversees it

Professional supervision is normally required. A regulator classifies this substance in a way that restricts how it is supplied.

Quoted from a source

Where this came from

Copied from a source RNAWiki stored, with the source named.

Suppression classes recorded: S8.

No source is stored against this line.

What is in the pack

Oral ergoline given as an adjunct to levodopa and carbidopa, titrated slowly from a low starting dose to limit nausea and orthostatic hypotension. Plasma half-life around 27 hours with extensive hepatic metabolism.

Source-linked record

Where this came from

A person wrote this into the record with the study named beside it. No reviewer has signed it off.

Recorded notes on how this is sold and what that means for what is in the pack.

No source is stored against this line.

Where it is registered

Regulatory records are listed in the technical disclosure at the foot of this page.

Counted from records

Where this came from

A count of rows RNAWiki holds. It describes our records, not your body.

Register entries are stored per jurisdiction and shown with their dates.

No source is stored against this line.

Why people stop

Not recorded.

Nothing recorded

Where this came from

RNAWiki holds nothing here and says so rather than guessing.

No record of why people stopped taking it is stored for this substance.

No source is stored against this line.

What it would be like to takeRead from sources, not yet reviewed

What can go wrong

Sorted by where each line came from. A regulator's label and a report somebody sent in are not the same kind of fact.

Worth asking a clinician aboutWritten into the record from the studies named on this page

Withdrawn from the United States market in March 2007 for cardiac valvulopathy. The measured harms are an incidence-rate ratio of 7.1 for newly diagnosed valve regurgitation and clinically important regurgitation in 23.4% of treated patients on echocardiography, both against a background where non-ergot dopamine agonists produced none. Risk increases with cumulative dose. Ergolines also carry retroperitoneal, pleural and pericardial fibrosis risk, and the class-wide dopamine agonist effects — impulse control disorders, sudden onset of sleep, orthostatic hypotension, hallucinations — apply as well.

Nobody counted how many people took this and were fine, so this cannot be turned into a rate.

Where this came from

Over a long time. No completed tested study window is recorded, so long-term effects are not established by the registry record.

Groups the studies covered thinly. Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.

What is missing or unclearRead from sources, not yet reviewed

Does the exact form matter?

Evidence belongs to the exact thing that was tested. A different salt, a different mixture or a different preparation is a different question.

The form that was studied

Oral tablet, three times daily, titrated over weeks

Source-linked record

Where this came from

A person wrote this into the record with the study named beside it. No reviewer has signed it off.

The form used in the studies cited on this page.

No source is stored against this line.

What is sold

Plasma half-life around 27 hours with extensive hepatic metabolism.

Source-linked record

Where this came from

A person wrote this into the record with the study named beside it. No reviewer has signed it off.

Recorded notes on which forms are sold and how they compare.

No source is stored against this line.

What is recorded as being sold

  • 6 products list this as an active ingredient in the United States drug directory. 6 of them contain it and nothing else.

    FDA National Drug Code directory · 47848-008 · read 2026-08-29

  • They are sold as powder.

    FDA National Drug Code directory · 47848-008 · read 2026-08-29

Evidence carries across two names for one substance. It does not carry across a salt, a mirror form or a mixture.

What it would be like to takeRead from sources, not yet reviewed

What you could measure

This one is decided with a clinician, so this section holds questions to ask rather than a plan to run.

Self-experiment planning is not offered for a prescription or clinician-supervised medicine, withdrawn medicine. The questions below are for a clinician or pharmacist.

Questions worth asking

  • Which of the trials of Pergolide studied people like me?
  • What was measured, and for how long?
  • Was the result a laboratory value or a health outcome?
  • What would we watch for, and when would we stop?

Tracking can show whether something changed for you. It cannot show what caused it.

RNAWiki records evidence. It does not say whether this substance is right for you.

What is missing or unclearRead from sources, not yet reviewed

Claims that go past the evidence

Things said about this substance that sound reasonable, and the exact step that is missing between the evidence and the claim.

Goes past the evidence

That the two ergot dopamine agonists carry interchangeable valvular risk — the significant findings differ by drug and by valve

Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.

The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.

What would change this

A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.

RNAWiki has not yet published a reviewed conclusion for this use.

Goes past the evidence

That non-significant tricuspid estimates on 64 and 49 patients constitute evidence of no tricuspid effect

Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.

The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.

What would change this

A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.

RNAWiki has not yet published a reviewed conclusion for this use.

What is missing or unclearRead from sources, not yet reviewed

What nobody knows yet

Open questions, each with why it is open and what would close it.

How much did people take in the studies?

The sources RNAWiki checked hold nothing for this field.

Why it matters. A result belongs to an amount. Without the amount the result floats free.

What would answer it

A stored source that records it, and a reviewer to sign it off.

Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.

Missing populations

Which groups were under-represented in the studies has not been recorded.

Why it matters. Recorded by the evidence model as a gap on this record.

What would answer it

A study that measures it, and a reviewer to sign it off.

Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.

Missing long-term data

No completed tested study window is recorded.

Why it matters. Recorded by the evidence model as a gap on this record.

What would answer it

A study that measures it, and a reviewer to sign it off.

Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.

No reviewed conclusion

RNAWiki has not yet published a reviewed conclusion for this use.

Why it matters. Recorded by the evidence model as a gap on this record.

What would answer it

A study that measures it, and a reviewer to sign it off.

Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.

Missing interaction studies

No interaction was found in the registers checked. Not finding one is not the same as showing there is none.

Why it matters. Recorded by the evidence model as a gap on this record.

What would answer it

A study that measures it, and a reviewer to sign it off.

Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.

Formulation uncertainty

Several salts, forms or products of Pergolide are recorded. Results from one form may not transfer to another.

Why it matters. Recorded by the evidence model as a gap on this record.

What would answer it

A study that measures it, and a reviewer to sign it off.

Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.

Mechanism not reviewed

No reviewed mechanism story exists for this substance.

Why it matters. Recorded by the evidence model as a gap on this record.

What would answer it

A study that measures it, and a reviewer to sign it off.

Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.

What happened in peopleRead from sources, not yet reviewed

Check any of this yourself

Every line above traced back to the study it came from. This is the technical layer, and the vocabulary changes here.

Every line above can be traced to the study named beside it. Follow the link and read it.

Incidence-rate ratio 7.1 for new valve regurgitation in 11,417 patients
In plain words
In a UK primary care database covering over eleven thousand people on Parkinson's drugs, new valve leakage was seven times more likely in those currently taking pergolide.
What was measured
Incidence-rate ratio for newly diagnosed cardiac-valve regurgitation by dopamine agonist
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Population-based cohort from the United Kingdom General Practice Research Database: 11,417 subjects aged 40 to 80 prescribed antiparkinsonian drugs between 1988 and 2005, with a nested case-control analysis matching each patient with newly diagnosed cardiac-valve regurgitation to up to 25 controls by age, sex and year of cohort entry. Of 31 case patients, 6 were currently exposed to pergolide, 6 to cabergoline, and 19 had not been exposed to any dopamine agonist in the previous year. The incidence-rate ratio was 7.1 for current pergolide use (95% CI 2.3 to 22.3) and 4.9 for cabergoline (95% CI 1.5 to 15.6). Current use of other dopamine agonists showed no increase.
Source
Schade R et al., N Engl J Med 2007;356:29-38
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
verified
Review state
Written into the record, not signed off as a reviewed claim
Echocardiography: 23.4% clinically important regurgitation, against 0% on non-ergot agonists
In plain words
Scanning 155 patients directly, about a quarter of those on pergolide had moderate or severe valve leakage. Among those on the non-ergot alternatives, not one did.
What was measured
Prevalence of grade 3 to 4 valve regurgitation on echocardiography, by dopamine agonist class
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Echocardiographic prevalence study in 155 patients taking dopamine agonists for Parkinson's disease — pergolide 64, cabergoline 49, non-ergot agonists 42 — and 90 control subjects, with regurgitation graded by American Society of Echocardiography criteria. Clinically important regurgitation (moderate to severe, grade 3 to 4) in any valve occurred in 23.4% on pergolide and 28.6% on cabergoline, against 0% on non-ergot-derived agonists and 5.6% in controls. Relative risks in the pergolide group were 6.3 for mitral regurgitation (p=0.008), 4.2 for aortic (p=0.01) and 5.6 for tricuspid (p=0.16); in the cabergoline group 4.6 (p=0.09), 7.3 (p<0.001) and 5.5 (p=0.12).
Source
Zanettini R et al., N Engl J Med 2007;356:39-46
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
verified
Review state
Written into the record, not signed off as a reviewed claim
A cumulative-dose relationship, and a quantitative index of leaflet stiffening
In plain words
Patients with the worst valve leakage had taken more of the drug in total, and a direct measurement of how stiff the valve leaflets were tracked the severity.
What was measured
Mitral-valve tenting area against regurgitation severity, and cumulative dose against regurgitation grade
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Zanettini and colleagues measured mitral-valve tenting area as a quantitative index of leaflet stiffening and apical displacement of leaflet coaptation. Mean tenting area was significantly greater in ergot-treated patients and showed a linear relationship with the severity of mitral regurgitation. Separately, ergot-treated patients with grade 3 to 4 regurgitation of any valve had received a significantly higher mean cumulative dose of pergolide or cabergoline than those with lower grades. A dose-response relationship plus a continuous structural measurement that tracks the graded outcome is a substantially stronger causal case than the regurgitation grades alone.
Source
Zanettini R et al., N Engl J Med 2007;356:39-46
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
verified
Review state
Written into the record, not signed off as a reviewed claim
Two independent designs, same journal issue, withdrawal within months
In plain words
A database study and a direct scanning study, done by different groups in different countries, were published together in January 2007. The drug was withdrawn in March.
What was measured
Not recorded
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The Schade nested case-control study drew on 11,417 UK primary care records and measured clinically diagnosed regurgitation; the Zanettini study scanned 155 Italian patients and 90 controls and measured echocardiographic grade and a structural index. The two designs have almost non-overlapping weaknesses — the first has a real denominator and depends on clinical diagnosis, the second detects subclinical disease and has a small sample — and they agreed. Both appeared in the New England Journal of Medicine on 4 January 2007. Pergolide was withdrawn from the United States market in March 2007 and appears in the FDA's codified withdrawn-for-safety list at 81 FR 69668 as "all drug products containing pergolide mesylate".
Source
Schade R et al., N Engl J Med 2007;356:29-38; Zanettini R et al., N Engl J Med 2007;356:39-46; FDA final rule 81 FR 69668
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
verified
Review state
Written into the record, not signed off as a reviewed claim
The same receptor that ended fenfluramine, ten years later, in a different class
In plain words
Fenfluramine was withdrawn in 1997 for valve damage caused by a specific serotonin receptor. Pergolide was withdrawn in 2007 for valve damage caused by the same receptor.
What was measured
Not recorded
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Fenfluramine's valvulopathy was traced to 5-HT2B agonism by its metabolite norfenfluramine, and the lesion was histopathologically identical to carcinoid and ergotamine valve disease. Pergolide is an ergoline and carries 5-HT2B agonism as a property of that scaffold. The non-ergot dopamine agonists do not, and produced 0% clinically important regurgitation in the echocardiographic study. So the pattern that was established for one indication in 1997 recurred in an entirely different indication a decade later, in a drug that had been marketed since 1988. The 5-HT2B counter-screen that the fenfluramine episode created is now applied to any candidate with serotonergic or ergoline chemistry, and it exists precisely because this failure repeats across classes.
Source
Zanettini R et al., N Engl J Med 2007;356:39-46; Connolly HM et al., N Engl J Med 1997;337:581-588
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
verified
Review state
Written into the record, not signed off as a reviewed claim
Fibrotic risk was assumed to belong to ergots generally, and clinically it does not divide that cleanly
In plain words
Both ergot-derived agonists caused valve damage, but not identically — pergolide hit the mitral valve hardest and cabergoline the aortic. Grouping them as one risk loses information a patient might need.
What was measured
That the ergot dopamine agonists carry an identical, interchangeable valvular risk profile
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The two ergot agonists differed by valve in the echocardiographic study. Pergolide relative risks were 6.3 for mitral (p=0.008), 4.2 for aortic (p=0.01) and 5.6 for tricuspid (p=0.16); cabergoline were 4.6 for mitral (p=0.09), 7.3 for aortic (p<0.001) and 5.5 for tricuspid (p=0.12). Only some of these reach significance, and the tricuspid estimates in both groups do not, on 64 and 49 patients respectively. Reporting "ergot agonists cause valve disease" is correct as a class statement and flattens a pattern in which the significant findings differ by drug and by valve, on samples small enough that the non-significant estimates are uninformative rather than negative.
Source
Zanettini R et al., N Engl J Med 2007;356:39-46
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
caution
Review state
Written into the record, not signed off as a reviewed claim
It is still in use — in horses
In plain words
Pergolide remains a standard veterinary treatment for a pituitary disorder in horses, where the same dopamine agonism is what is wanted and the risk calculus is different.
What was measured
Not recorded
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Pergolide is used in equine medicine for pituitary pars intermedia dysfunction, where D2 agonism suppresses the pars intermedia melanotrope hyperactivity that drives the condition. The withdrawal recorded at 81 FR 69668 applies to human drug products. This is a straightforward illustration of the point the whole file makes: a withdrawal is a judgement about a specific benefit-risk trade in a specific population, not a statement that a molecule is inherently unfit. Change the species, the alternatives available and the life expectancy of the patient, and the arithmetic changes with them.
Source
FDA final rule 81 FR 69668, 7 October 2016 — human drug products containing pergolide mesylate
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
verified
Review state
Written into the record, not signed off as a reviewed claim

Where else this substance is registered

FDA substance identifier (UNII)
24MJ822NZ9
CAS registry number
66104-22-1
PubChem compound
47811
ChEMBL
CHEMBL531
ChEBI
63617
WHO international nonproprietary name list entry
4651
RxNorm concept
8047
EMA substance identifier
100000082732
DrugBank
DB01186

Checks this page had to pass

  • Passed

    Identity resolved

    no open identity hold

  • Passed

    No unresolved merge across substance families

    no quarantine open

  • Passed

    Every public sentence names a source

    The opening statement carries the origin: Written into the record, not signed off.

  • Not passed

    Trial roles classified for highlighted evidence

    No registered study is classified as testing this substance.

  • Passed

    No internal keys in reader text

    enforced by the copy-contract test over the rendered page

  • Passed

    Safety mode resolved

    Suppression classes recorded: S8.

  • Passed

    Canonical metadata present

    slug and display name present

What is missing or unclearRead from sources, not yet reviewed

How this medicine reached us

Kept near the foot of the page. A historical event moves up only when it changes something about this substance today.

  1. Withdrawn in United States; Canada, 2007, for "cardiotoxicity" (ChEMBL; Open Targets)

What the approval register records

  • 3 approved applications cover products containing this substance. The earliest was NDA019385, approved 19881230 to VALEANT PHARM INTL.

    Drugs@FDA application register · NDA019385 · read 2026-08-29

  • Marketing status on the register: discontinued.

    Drugs@FDA application register · NDA019385 · read 2026-08-29

  • The earliest marketing start date recorded for a listed product is 20130107.

    FDA National Drug Code directory · 47848-008 · read 2026-08-29

What is missing or unclearRead from sources, not yet reviewed

What to learn next

Ordered by what would most change how you read this page, starting with what is easiest to misunderstand.

This order is fixed in code and does not count clicks or time on the page.

What is not here

7 questions this page could not answer

These sections were prepared and left out because there was nothing to put in them. They are listed rather than hidden, so the gaps in this record are visible.

  • What was measured, goal by goal — found nothing in the sources checked.
  • How close this is to real life — found nothing in the sources checked.
  • Felt, measured, or meaningful — found nothing in the sources checked.
  • How long anything takes — found nothing in the sources checked.
  • What it may clash with — found nothing in the sources checked.
  • Other ways to the same goal — found nothing in the sources checked.
  • What changed on this page — found nothing in the sources checked.

The record as stored

The full record, for auditing

Everything above is built from what is below. This layer keeps the technical vocabulary, record identifiers and every stored row, so a reader who wants to check the page can.

The older medicine-wide conclusion held in this record

Written for a clinical reader, and about the medicine as a whole rather than about one indication, population and set of trials. RNAWiki does not treat it as a programme conclusion and no reviewer has signed it off in that form. It is here word for word because it is what the record holds.

An ergot-derived dopamine agonist withdrawn in 2007 after two independent studies published in the same journal issue found a 7.1-fold incidence-rate ratio for new valve regurgitation and clinically important regurgitation in 23.4% of treated patients against 5.6% of controls — while non-ergot agonists produced none.

Recorded evidence blocks (6)

9 registered trials of Pergolide — at which phases?


Registered studies posting no result
9 of 9

9 registered studies of Pergolide: 3 na, 2 na or unstated, 2 phase2, 2 phase3. CLINICALTRIALS_SNAPSHOT · 2026-09-01

132 with a PubMed record

Show the evidence
  • na
    3
  • na or unstated
    2
  • phase2
    2
  • phase3
    2
  • completed
    6
  • no longer available
    1
2 more recorded rows
  • suspended
    1
  • unknown
    1

recorded 2026-09-01 · last checked 2026-09-04

Approved in 1988, withdrawn in 2007: what happened to Pergolide in United States; Canada?


Approved 1988, withdrawn 2007 in United States; Canada; the register's words: "cardiotoxicity". Open Targets drug warning · CHEMBL1275 · 2026-06-24

2 recorded reasons; United States; Canada

Show the evidence

Reason

  • "cardiotoxicity"
  • "cardiotoxicity"

recorded 2026-06-24 · last checked 2026-09-04

Which 5 trials of Pergolide posted no result?


Posted no result
5 of 5 completed trials
Registrations
NCT00000215, NCT00000269, NCT00004433, NCT01066403 and NCT00605683
Completion dates
oldest 2001-12; newest 2012-03
Show the evidence

Trial

  • NCT00000215
    2001-12
  • NCT00000269
    2001-12
  • NCT00004433
    2002-09
  • NCT01066403
    2008-03
  • NCT00605683
    2012-03

At the median, Pergolide's trials enrolled 20 people — anything larger?


Median enrolment
20
Largest enrolment
679
Registered trials counted
7

What do 285 spontaneous reports say about Pergolide — and not say?


These are reports people sent to a regulator. They do not show the medicine caused the reaction. Nobody counted how many people took the medicine and reported nothing. The same event can be reported more than once, and many reports are incomplete. News coverage, lawsuits and new warnings change how often people report. A count is not a rate and not a risk.

Pergolide appears in spontaneous reports to regulators. Across the 10 most-reported reaction terms, 285 reaction mentions were counted: mitral valve incompetence 47; aortic valve incompetence 44; cardiac valve disease 35; tricuspid valve incompetence 30. FAERS via Open Targets · CHEMBL1275 · 2026-06-24

Show the evidence
  • mitral valve incompetence
    47
  • aortic valve incompetence
    44
  • cardiac valve disease
    35
  • tricuspid valve incompetence
    30
  • cardiac failure
    28
  • dyspnoea
    25
4 more recorded rows
  • mitral valve disease
    22
  • pleural effusion
    22
  • oedema peripheral
    17
  • condition aggravated
    15

recorded 2026-06-24 · last checked 2026-09-04

Where do the label and the trials disagree about Pergolide?


"cardiotoxicity" against "approved": withdrawal status vs register status for Pergolide.

OPEN_TARGETS_DRUG_WARNING, Drugs@FDA; 1 recorded pair

Show the evidence
  • OPEN_TARGETS_DRUG_WARNING CHEMBL1275
    cardiotoxicity; 2026-06-24
  • Drugs@FDA NDA019385
    approved; 2026-08-28
Where it is registered

Where it’s registered

Withdrawn in United States; Canada, 2007, for "cardiotoxicity" (ChEMBL; Open Targets)

Identifiers, relations and other names

The exact record

ChEMBL id
CHEMBL1275
PubChem CID
47812
CAS number
66104-23-2
RxCUI
8048
InChIKey
YEHCICAEULNIGD-MZMPZRCHSA-N
Also called
PERGOLIDE MESYLATE, Pergolide mesilate, Pergolide methanesulfonate, Pergolida, PERGOLIDE [MI], PERGOLIDE [VANDF], Pergolide [WHO-DD], pergolide [INN]
Trade name
Celance, Permax
Development code
LY 127809, NSC-319773, NSC-758442
Sources (5)

Sources

ChEMBL 37 — CC BY-SA 3.0 Unported · ClinicalTrials.gov — US Government work · Open Targets 26.06 — CC0 · mixed register set; per-register licences in docs/specs/corpus-20k-sources.md

How these records are assembled · Which registers were checked

Index-quality checks
  • identity passed: no open identity hold
  • required summary fields resolved: 4 required field(s) not terminal: Why people use it, Best-supported result, Biggest unanswered question, Human evidence
  • public claims reviewed: 0 reviewed claim(s); drafts are never rendered
  • source coverage passed: 5 source rows
  • no critical contamination: no quarantine open
  • canonical metadata passed: slug and display name present
  • no raw internal fields: enforced by the copy-contract test over the rendered page

This is a record of evidence. It is not medical advice, and it does not say this substance suits you. Nothing here says any substance on RNAWiki is appropriate for a child.