This page shows what was measured, who it was measured in, and what that does not settle.
What Rapacuronium does in the body
Rapacuronium blocks that brake about fifteen times more strongly than it blocks the receptor that actually constricts the airway.
Rapacuronium paralyses muscle by blocking the nerve signal at the muscle. The problem is elsewhere. Nerves supplying the airway have a built-in brake: a receptor on the nerve ending that senses how much acetylcholine has been released and shuts off further release. So during intubation, when those nerves are firing hard, the brake fails, acetylcholine floods out, and the airway clamps shut in a patient who has just been paralysed.
Why people take it. Formerly used during anaesthesia to relax muscles for placement of a breathing tube.
What happened in people
Laboratory studies showed it removed a nerve brake on airway tightening at the amounts patients received.
✓ 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 airway reaction was neither an allergy nor a histamine reaction.
Where it acts
Neuromuscular junction for the intended effect; the toxicity site is the airway smooth muscle and the parasympathetic nerves supplying it
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 · GG1LBM463S · read 2026-08-29
Its recorded molecular formula is C37H61N2O4+, weighing 597.9.
PubChem record · 5311399 · 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 118 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.
Biomarker
A biomarker is a number from a test that stands in for something about health.
A picture of it, and where the picture fails
A biomarker is like a fuel gauge.
Where that stops being true. A gauge is wired to the tank. Many biomarkers are only loosely tied to health.
What people get wrong. A better number is read as a better life. Several medicines improved a number and helped nobody.
A measurable indicator used as a substitute for a clinical outcome of interest.
Placebo
A placebo is a dummy treatment given so the real one can be compared with it.
A picture of it, and where the picture fails
A placebo is like a blank control in an experiment.
Where that stops being true. A blank does nothing. People given a placebo often do get better.
What people get wrong. A placebo effect is read as imaginary. The improvement is measured and real.
An inactive intervention matched in appearance to the test intervention, used to control for non-specific effects.
Comparator
A comparator is whatever the treatment was measured against.
A picture of it, and where the picture fails
It is like the other runner in a race.
Where that stops being true. A race has one winner. A study can show both arms improved.
What people get wrong. Results are read without asking what the other group got. Beating nothing is not beating a treatment.
The control condition against which the experimental intervention is assessed.
What happened in people◇Read 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.
Half-maximal inhibitory concentrations of rapacuronium, vecuronium and cisatracurium at M2 versus M3 muscarinic receptors, referenced to clinically achieved concentrations
✓ The study showed what it set out to show
Who was studied
Competitive radioligand binding at M2 and M3 muscarinic receptors (Jooste et al.)
How many people
14
Study design
Mechanistic receptor pharmacology
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
Rapacuronium IC50 5.10 ± 1.5 micromolar at M2 (n = 6) and 77.9 ± 11 micromolar at M3 (n = 8); vecuronium and cisatracurium bound both receptors only above clinically achieved concentrations
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. Binding affinity alone does not predict the allosteric potentiation later demonstrated at M3, so the 2003 result understates the mechanism it identified.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Single intravenous bolus at induction of anaesthesia
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
21 CFR 216.24 — Drug products withdrawn or removed from the market for reasons of safety or effectiveness (entry: rapacuronium bromide) (https://www.ecfr.gov… · a recorded source, not a stored snapshot
Drugs@FDA: RAPLON (rapacuronium bromide), NDA 020984, Organon USA Inc — Discontinued (https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overvie… · a recorded source, not a stored snapshot
Airway smooth muscle force in the presence and absence of subthreshold acetylcholine, and allosteric interaction at recombinant human M3
✓ The study showed what it set out to show
Who was studied
Guinea pig tracheal ring and recombinant M3 allosteric study
How many people
1
Study design
Mechanistic airway pharmacology and receptor kinetics
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
Contraction within clinically achieved concentrations only with subthreshold acetylcholine present; prevented or reversed only by atropine; slowed atropine-induced [3H]-N-methylscopolamine dissociation and potentiated acetylcholine-induced inositol phosphate synthesis
Repeated elsewhere
Partially 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. Guinea pig tracheal rings are a standard airway model but not human tissue, and the recombinant receptor work is in transfected cells rather than native airway.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Single intravenous bolus at induction of anaesthesia
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
21 CFR 216.24 — Drug products withdrawn or removed from the market for reasons of safety or effectiveness (entry: rapacuronium bromide) (https://www.ecfr.gov… · a recorded source, not a stored snapshot
Drugs@FDA: RAPLON (rapacuronium bromide), NDA 020984, Organon USA Inc — Discontinued (https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overvie… · a recorded source, not a stored snapshot
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 body◇Read 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.
Start
Rapacuronium
What a person takes: Single intravenous bolus at induction of anaesthesia.
The measurement behind this step
Intravenous rapacuronium bromide given as a single bolus for rapid-sequence tracheal intubation, with onset around 60 seconds and short duration. Hydrolysed to a 3-desacetyl metabolite that is itself an active neuromuscular blocker with longer duration than the parent.
Getting in
A single intravenous bolus at induction of anaesthesia
Injected into a vein as anaesthesia begins, to produce paralysis within about a minute so a breathing tube can be placed.
╌╌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
Single intravenous bolus of rapacuronium bromide for rapid-sequence induction. Onset within approximately 60 seconds with short duration, the profile that was its entire reason for existing.
21 CFR 216.24 — Drug products withdrawn or removed from the market for reasons of safety or effectiveness (entry: rapacuronium bromide) (https://www.ecfr.gov… · a recorded source, not a stored snapshot
Reaching the cell
Distributes to the neuromuscular junction and to airway tissue
It reaches the junctions between nerve and muscle throughout the body, including the nerves supplying the airways.
╌╌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
A pre-formed quaternary cation, so it stays extracellular and does not cross the blood-brain barrier. It reaches nicotinic receptors at the motor endplate and muscarinic receptors on airway parasympathetic nerve terminals and smooth muscle at the same time.
21 CFR 216.24 — Drug products withdrawn or removed from the market for reasons of safety or effectiveness (entry: rapacuronium bromide) (https://www.ecfr.gov… · a recorded source, not a stored snapshot
What it acts on
Blocks nicotinic receptors — and prejunctional M2 fifteen times more than M3
It paralyses muscle as intended. It also blocks the nerve-ending brake far more strongly than it blocks the airway-constricting receptor.
╌╌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
Competitive antagonism at the nicotinic acetylcholine receptor produces neuromuscular blockade. Simultaneously, IC50 of 5.10 micromolar at M2 against 77.9 micromolar at M3 means prejunctional autoinhibition is blocked while postjunctional constriction is not, and positive allosteric cooperativity at M3 potentiates acetylcholine further.
21 CFR 216.24 — Drug products withdrawn or removed from the market for reasons of safety or effectiveness (entry: rapacuronium bromide) (https://www.ecfr.gov… · a recorded source, not a stored snapshot
The change it makes
Intubation drives acetylcholine release with the brake removed
Placing the tube stimulates those airway nerves hard. Normally the brake limits how much signal they release; here it cannot.
╌╌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
Parasympathetic nerve stimulation during intubation triggers acetylcholine release. With prejunctional M2 autoinhibition blocked, release is unopposed, and the accumulated acetylcholine acts on M3 receptors whose response is allosterically potentiated by the same drug.
21 CFR 216.24 — Drug products withdrawn or removed from the market for reasons of safety or effectiveness (entry: rapacuronium bromide) (https://www.ecfr.gov… · a recorded source, not a stored snapshot
What that does for a person
Paralysis achieved; the airway closes in a patient who cannot breathe
The drug worked as a muscle relaxant. In some patients, especially children, the airway clamped shut at the moment they were most dependent on it staying open.
╌╌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
Measured: rapid effective neuromuscular blockade. Measured: airway smooth muscle contraction within clinically achieved concentrations in the presence of subthreshold acetylcholine, reversible only by atropine. Post-marketing: severe and fatal bronchospasm, disproportionately in children, leading to withdrawal nineteen months after approval.
21 CFR 216.24 — Drug products withdrawn or removed from the market for reasons of safety or effectiveness (entry: rapacuronium bromide) (https://www.ecfr.gov… · a recorded source, not a stored snapshot
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 unclear◇Read 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.
Nobody. Rapacuronium appears in 21 CFR 216.24 as a drug product withdrawn for reasons of safety or effectiveness.
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
Approved August 1999 and voluntarily withdrawn March 2001, nineteen months later, for severe and fatal bronchospasm
Listed in 21 CFR 216.24 as "all drug products containing rapacuronium bromide"
The receptor selectivity that caused the deaths is measurable in a binding assay that was not part of the development programme
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 take◇Read 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 take◇Read 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
Single intravenous bolus at induction of anaesthesia
✎ 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
Intravenous rapacuronium bromide given as a single bolus for rapid-sequence tracheal intubation, with onset around 60 seconds and short duration. Hydrolysed to a 3-desacetyl metabolite that is itself an active neuromuscular blocker with longer duration than the parent.
✎ 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 take◇Read 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 in March 2001 for severe and fatal bronchospasm, reported disproportionately in children. The mechanism is muscarinic and not allergic: fifteen-fold selectivity for M2 over M3 within clinically achieved concentrations removes prejunctional autoinhibition of acetylcholine release during the parasympathetic stimulation of intubation, while positive allosteric cooperativity at M3 potentiates the resulting bronchoconstriction. The effect is reversible only by atropine. Standard non-depolarising blocker hazards — residual paralysis, the need for airway control throughout — apply as well.
Nobody counted how many people took this and were fine, so this cannot be turned into a rate.
21 CFR 216.24 — Drug products withdrawn or removed from the market for reasons of safety or effectiveness (entry: rapacuronium bromide) (https://www.ecfr.gov… · a recorded source, not a stored snapshot
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 unclear∅Nothing found in the sources checked
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
Single intravenous bolus at induction of anaesthesia
✎ 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
Hydrolysed to a 3-desacetyl metabolite that is itself an active neuromuscular blocker with longer duration than the parent.
✎ 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.
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 take◇Read 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 Rapacuronium 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 unclear◇Read 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 bronchospasm was anaphylactic or histamine-mediated; histamine, neurokinin, leukotriene and calcium channel mechanisms were excluded experimentally
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 a resting-tissue airway screen would have detected the hazard — the effect requires a background of parasympathetic acetylcholine release
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 unclear◇Read 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 Rapacuronium 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 people◇Read 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.
Fifteen-fold M2 over M3 selectivity, inside the clinical concentration range
In plain words
Rapacuronium blocks the nerve-ending brake about fifteen times more strongly than the receptor that constricts the airway — and it does so at the concentrations patients actually receive.
What was measured
Half-maximal inhibitory concentration at M2 versus M3 muscarinic receptors, against clinically achieved concentrations
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Competitive radioligand binding measured the affinities of rapacuronium, vecuronium, cisatracurium, methoctramine and 4-DAMP at M2 and M3 muscarinic receptors. Rapacuronium competitively displaced [3H]-quinuclidinyl benzilate from M2 but not from M3 within clinically relevant concentrations, with half-maximal inhibitory concentrations of 5.10 plus or minus 1.5 micromolar at M2 (n = 6) and 77.9 plus or minus 11 micromolar at M3 (n = 8). Cisatracurium and vecuronium displaced the ligand from both receptors, but only at concentrations above those achieved clinically for those relaxants. The proposed mechanism follows directly: blockade of prejunctional M2 receptors on parasympathetic nerves increases acetylcholine release, which then acts on unopposed M3 receptors in airway smooth muscle to produce constriction.
Written into the record, not signed off as a reviewed claim
It does not just fail to block M3 — it makes acetylcholine work better
In plain words
Later work found rapacuronium actively enhances the airway-constricting signal, a property unique to it among muscle relaxants at clinical doses.
What was measured
Positive cooperativity at M3 measured by potentiation of acetylcholine-induced inositol phosphate synthesis and slowed antagonist dissociation
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
In guinea pig tracheal rings, rapacuronium within clinically achieved concentrations contracted airway smooth muscle in the presence but not in the absence of subthreshold acetylcholine, and the effect was prevented or reversed only by atropine — not by histamine, neurokinin or leukotriene antagonism, L-type calcium channel blockade, or depletion of non-adrenergic non-cholinergic transmitters. Allosteric action was demonstrated by slowing of atropine-induced dissociation of [3H]-N-methylscopolamine, and positive cooperativity by potentiation of acetylcholine-induced inositol phosphate synthesis at recombinant human M3. Many muscle relaxants have allosteric properties at muscarinic receptors; positive cooperativity at M3 within clinically relevant concentrations is unique to rapacuronium.
Written into the record, not signed off as a reviewed claim
The assay that would have caught it required an acetylcholine background
In plain words
Test the drug on airway muscle by itself and nothing happens. Test it against a low background of the natural signal, as occurs during intubation, and the airway contracts.
What was measured
Not recorded
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Rapacuronium contracted tracheal rings in the presence but not in the absence of subthreshold acetylcholine. A conventional airway safety screen — apply the compound to a resting preparation and look for contraction — returns a negative result, correctly, because the drug does not constrict anything on its own. The harm requires ongoing parasympathetic activity, which is precisely what tracheal intubation provokes. The condition under which the drug is dangerous is the condition under which it is given, and it is not the condition a resting-tissue assay reproduces. This is a general lesson about counter-screens: an assay measures what its background permits it to measure.
Written into the record, not signed off as a reviewed claim
Nineteen months from approval to withdrawal
In plain words
Approved in August 1999, withdrawn in March 2001. It is now on the federal list of drugs removed for safety reasons.
What was measured
Not recorded
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
Drugs@FDA records NDA 020984 for RAPLON, Organon USA Inc, with products in Discontinued marketing status. The product was voluntarily withdrawn in March 2001 after post-marketing reports of severe and fatal bronchospasm, particularly in children. 21 CFR 216.24 carries the entry "Rapacuronium bromide: All drug products containing rapacuronium bromide". The short interval reflects the setting rather than any unusual vigilance: bronchospasm immediately after induction of anaesthesia is witnessed by a specialist, timed to the minute, and attributed to a drug given seconds earlier. Almost no other adverse event in this file is observed under those conditions, which is why almost no other took nineteen months to act on.
Written into the record, not signed off as a reviewed claim
The harm concentrated in children
In plain words
The bronchospasm reports were disproportionately in paediatric patients, whose airways are smaller and whose parasympathetic tone is higher.
What was measured
Dependence of the bronchoconstrictor effect on background parasympathetic acetylcholine release
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The reported cases of severe and fatal bronchospasm occurred disproportionately in children. Two features of paediatric airway physiology are consistent with this: resistance rises with the fourth power of the reciprocal of radius, so a given degree of smooth muscle constriction produces far greater obstruction in a small airway; and baseline parasympathetic tone is higher in children, which matters directly for a mechanism that requires ongoing acetylcholine release to manifest. The mechanistic work establishes why the effect depends on parasympathetic activity, and the paediatric preponderance follows from that rather than being a separate observation.
Written into the record, not signed off as a reviewed claim
The mechanistic work was done after withdrawal, on purpose
In plain words
The receptor studies were published two and four years after the drug was gone, explicitly so that future muscle relaxants would be screened for the same property.
What was measured
Not recorded
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Both mechanistic papers state their rationale in the same terms: understanding how rapacuronium induces fatal bronchospasm is imperative so that newly synthesised neuromuscular blocking agents sharing this mechanism are not introduced clinically, and the findings establish parameters that should be considered in evaluating the airway safety of any new candidate in the class. This is a case where the scientific value of the investigation lies entirely outside the drug investigated. The 2003 and 2005 studies produced a screening specification — M2 versus M3 affinity against clinical concentration, and allosteric cooperativity at M3 — that did not exist when rapacuronium was developed.
Written into the record, not signed off as a reviewed claim
It was not an allergic reaction, and calling it one would have hidden the mechanism
In plain words
Bronchospasm under anaesthesia is usually treated as an allergic or histamine reaction. Here it was neither, and the studies ruled those out directly.
What was measured
That rapacuronium bronchospasm was an anaphylactic or histamine-mediated reaction
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The tracheal ring experiments tested the alternatives explicitly. The rapacuronium contraction was prevented or reversed only by atropine — a muscarinic antagonist — and not by antagonism of histamine, neurokinin or leukotriene receptors, by L-type calcium channel blockade, or by depletion of non-adrenergic non-cholinergic transmitters. Neuromuscular blockers are the commonest cause of perioperative anaphylaxis, so an allergic attribution was the available default and would have been accepted. It would also have produced the wrong conclusion for the class: an idiosyncratic allergy is a property of a patient, whereas a fifteen-fold M2-over-M3 selectivity is a property of a molecule that can be measured in advance of the first human dose.
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A rapid-onset non-depolarising muscle relaxant withdrawn nineteen months after approval for fatal bronchospasm, with the mechanism subsequently quantified as a fifteen-fold selectivity for the M2 muscarinic receptor over M3 — half-maximal inhibitory concentrations of 5.10 plus or minus 1.5 micromolar against 77.9 plus or minus 11 micromolar — which removes the brake on acetylcholine release while leaving airway constriction intact.
Recorded evidence blocks (2)
Q2
Approved in 1999, withdrawn in 2001: what happened to Rapacuronium in United States?
ChEMBL 37 — CC BY-SA 3.0 Unported · Open Targets 26.06 — CC0 · PubMed — US Government work · mixed register set; per-register licences in docs/specs/corpus-20k-sources.md
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