This page shows what was measured, who it was measured in, and what that does not settle.
What Clioquinol does in the body
An oral anti-diarrhoea and amoebic dysentery drug, sold for decades including without prescription
Clioquinol grips metal ions — zinc, copper, iron — using a chemical claw. In the gut that was thought to be all it did, killing amoebae locally without being absorbed. It was absorbed. Once inside the body the same metal-gripping chemistry disrupts cell metabolism, and recent work shows it inactivates the active form of vitamin B1, which mitochondria need to burn fuel. The long nerve fibres of the spinal cord and optic nerve, which have the highest energy demands and the least margin, degenerate first.
What happened in people
Clinical syndrome of subacute sensory and motor disturbance of the lower limbs with visual impairment, preceded by abdominal symptoms
✎ 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 recorded finding that sits closest to something a person would notice. Written into the record, not signed off, and it carries no population or interval.
That a drug acting in the intestinal lumen carries no systemic risk — the assumption that licensed decades of broad use
Where it acts
Intestinal lumen for the intended effect; the toxicity sites are the posterior columns of the spinal cord and the optic nerves
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 · 7BHQ856EJ5 · read 2026-08-29
Its recorded molecular formula is C9H5ClINO, weighing 305.5.
PubChem record · 2788 · read 2026-08-29
Where each sentence above came from
No recorded sentence describes the change this makes in a way that stands on its own. The page opens with what it is taken for instead, and the recorded explanation follows below.
Shown as the opening line on this page.
A limit recorded against this substance. Not signed off as a reviewed claim.
The four opening statements run to 117 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.
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.
Randomisation
Randomisation means chance decides who gets which treatment.
A picture of it, and where the picture fails
It is like a coin toss deciding the groups.
Where that stops being true. A coin toss is fair once. Fairness here comes from doing it for everyone.
What people get wrong. It is thought to make groups identical. It makes them similar on average, including on things nobody measured.
Allocation of participants to arms by a chance process, so that unmeasured factors are balanced in expectation.
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.
Cognitive change on the Alzheimer's Disease Assessment Scale cognitive subscale, with plasma amyloid beta 42 as a biomarker
✓ The study showed what it set out to show
Who was studied
Pilot phase 2 trial of clioquinol in Alzheimer's disease (Ritchie et al.)
How many people
36
Study design
Pilot phase 2 randomised trial
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
Significant effect confined to the subgroup with baseline ADAS-cog of 25 or above, driven by worsening on placebo against minimal deterioration on clioquinol; plasma amyloid beta 42 fell on clioquinol and rose on placebo; plasma zinc rose
Repeated elsewhere
Unreplicated
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. Thirty-six randomised patients with the effect confined to a severity subgroup, and the difference driven by the control arm. The authors state the small-sample caveats explicitly.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral tablet, historically also topical cream and ear drops
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
Identification of the pathways mediating clioquinol neurotoxicity, including thiamine pyrophosphate status, mitochondrial respiration and metal handling
✓ The study showed what it set out to show
Who was studied
Mechanistic characterisation in human neuroblastoma cells and an Alzheimer's model
How many people
1
Study design
Laboratory mechanistic investigation across cell and animal models
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
Oxidative inactivation of thiamine pyrophosphate with diminished oxidative phosphorylation and compensatory glycolysis; separately, DNA double-strand breaks with ATM/p53 activation, zinc influx and oxidation of the copper chaperone ATOX1 impairing dopamine-beta-hydroxylase
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. Multiple candidate pathways have been demonstrated and no single one has been shown to be sufficient, so the mechanism is described in the review literature as multifactorial rather than settled.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral tablet, historically also topical cream and ear drops
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
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
Clioquinol
What a person takes: Oral tablet, historically also topical cream and ear drops.
The measurement behind this step
Oral clioquinol was given in repeated or prolonged courses, in Japan frequently for non-specific abdominal symptoms rather than amoebiasis. Systemic absorption, long assumed negligible, is substantial and the lipophilic metal chelates cross membranes including into the central nervous system.
Getting in
An oral tablet, often taken repeatedly over long periods
Swallowed for abdominal symptoms and diarrhoea, frequently in long or repeated courses.
╌╌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
Oral clioquinol given for amoebiasis and, far more commonly in Japan, for non-specific abdominal symptoms. The breadth of indication and the length of courses both rested on an assumption of negligible absorption.
Absorbed systemically, contrary to the design assumption
It was supposed to stay in the gut. It did not — the metal complexes it forms are exactly the kind of molecule that crosses membranes.
╌╌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
The lipophilic metal chelates formed by the 8-hydroxyquinoline motif cross biological membranes readily, giving systemic exposure and central nervous system penetration that the intestinal-antiseptic framing did not anticipate.
Chelates zinc, copper and iron; raises oxidative stress
Inside cells it grips metal ions and shifts them around, which increases chemical stress on the cell.
╌╌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
Bidentate chelation of divalent metals through the phenolic oxygen and ring nitrogen redistributes zinc and copper across membranes, acting as an ionophore. Cellular oxidative stress rises, with no single protein target involved.
Thiamine pyrophosphate is oxidised and mitochondria fail
The stress destroys the active form of vitamin B1. Without it, mitochondria cannot burn fuel properly and the cell falls back on a much less efficient route.
╌╌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
Oxidative modification inactivates thiamine pyrophosphate, the cofactor for pyruvate dehydrogenase, alpha-ketoglutarate dehydrogenase and transketolase. Oxidative phosphorylation falls with compensatory glycolysis, and mitochondrial morphology degrades in a TPP-dependent manner.
Long axons degenerate: numbness, weakness, blindness
The longest nerve fibres — those running the length of the spinal cord and to the eye — have the least energy margin and die first, causing numbness rising from the feet, weakness and visual loss.
╌╌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
Axonopathy of the spinal cord posterior columns and optic nerves, producing subacute ascending sensory and motor disturbance of the lower limbs with visual impairment, preceded by abdominal symptoms. Rescue by thiamine pyrophosphate or N-acetylcysteine in animal models confirms the energetic pathway.
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 orally. Topical clioquinol preparations for skin and ear remained available in some markets, and the compound is now studied as a research chelator rather than used as an oral drug.
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 the 1930s and used at scale in Japan for ordinary abdominal complaints, an indication far broader than amoebiasis
Oral use banned in Japan in September 1970 after epidemiological linkage to subacute myelo-optic neuropathy
The mechanism was still described as incompletely understood in 2024, more than fifty years after the ban
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
Oral tablet, historically also topical cream and ear drops
✎ 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 clioquinol was given in repeated or prolonged courses, in Japan frequently for non-specific abdominal symptoms rather than amoebiasis. Systemic absorption, long assumed negligible, is substantial and the lipophilic metal chelates cross membranes including into the central nervous system.
✎ 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
Oral use was banned in Japan in September 1970 after epidemiological linkage to subacute myelo-optic neuropathy: subacute onset of sensory and motor disturbance in the lower extremities with occasional visual impairment, preceded by abdominal symptoms, on a background of axonopathy of the spinal cord and optic nerves. Visual loss was frequently permanent. The mechanism is now characterised as oxidative inactivation of thiamine pyrophosphate leading to mitochondrial failure, with mitigation by thiamine pyrophosphate or N-acetylcysteine demonstrated in animal models. Green discoloration of the tongue, urine and faeces from metal chelates was a recognised marker of exposure.
Nobody counted how many people took this and were fine, so this cannot be turned into a rate.
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◇Read 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, historically also topical cream and ear drops
✎ 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
Systemic absorption, long assumed negligible, is substantial and the lipophilic metal chelates cross membranes including into the central nervous system.
✎ 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
5 products list this as an active ingredient in the United States drug directory. 4 of them contain it and nothing else.
FDA National Drug Code directory · 38779-0032 · read 2026-08-29
They are sold as cream and powder, taken topical.
FDA National Drug Code directory · 38779-0032 · read 2026-08-29
1 published label names it as an active ingredient. None of them describes this substance alone, so no label text on this page can be attributed to it rather than to a combination.
US prescribing information · 134a88a1-13e5-4da0-8270-c380b57aaeb7 · read 2026-08-29
Those labels are classed as human otc drug.
US prescribing information · 134a88a1-13e5-4da0-8270-c380b57aaeb7 · 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 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 Clioquinol 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 a drug acting in the intestinal lumen carries no systemic risk — the assumption that licensed decades of broad use
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 the 36-patient Alzheimer's pilot demonstrated clinical benefit; the effect was subgroup-restricted and control-arm-driven
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 the delay to a molecular mechanism weakened the epidemiological case for causation
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 Clioquinol 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.
The syndrome was defined and linked to the drug in 1971
In plain words
Japanese neurologists described a distinctive pattern — numbness and weakness rising from the feet, often with visual loss, preceded by abdominal symptoms — and connected it to clioquinol.
What was measured
Clinical syndrome definition and epidemiological association with clioquinol exposure
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Subacute myelo-optic neuropathy is characterised by subacute onset of sensory and motor disturbance in the lower extremities with occasional visual impairment, preceded by abdominal symptoms. The association with clioquinol was reported in the Lancet in 1971, and pathological studies subsequently demonstrated axonopathy of the spinal cord and optic nerves. The abdominal prodrome is the diagnostically decisive feature and the epidemiologically treacherous one: the symptoms that prompted the drug and the earliest symptoms of the poisoning are the same, so each episode of abdominal discomfort produced more exposure.
Written into the record, not signed off as a reviewed claim
The epidemic ended when the drug was banned
In plain words
Oral clioquinol was banned in Japan in September 1970. New cases of the syndrome stopped appearing.
What was measured
Incidence of subacute myelo-optic neuropathy in Japan before and after the September 1970 ban
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Clioquinol was withdrawn from the market in Japan because its use was epidemiologically linked to an increase in the incidence of subacute myelo-optic neuropathy. The cessation of new cases after the September 1970 ban is the strongest single piece of evidence in the case, and it is a natural experiment rather than a designed one: an abrupt, near-total removal of a single exposure from an entire national population, followed by the disappearance of a distinctive syndrome that had been accumulating for years. No randomised trial of this exposure was ever conducted or could have been, and none was needed to establish causation at this level of confidence.
Written into the record, not signed off as a reviewed claim
The mechanism: oxidative inactivation of thiamine pyrophosphate
In plain words
Recent work found that clioquinol destroys the active form of vitamin B1, which mitochondria need. Adding that vitamin back, or an antioxidant, prevents the nerve damage in animals.
What was measured
Cerebral thiamine pyrophosphate concentration and mitochondrial respiration under clioquinol, with rescue by TPP or N-acetylcysteine
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Metabolomic analysis identified thiamine pyrophosphate as the key metabolite affected by clioquinol. The drug promotes its inactivation through oxidative modification; extracellular flux analysis showed the resulting deficiency diminished mitochondrial oxidative phosphorylation with compensatory glycolysis, and electron microscopy showed mitochondrial damage in a thiamine-pyrophosphate-dependent manner. In an Alzheimer's disease murine model, clioquinol provoked oxidative stress, decreased cerebral thiamine pyrophosphate and induced neuronal injury; supplementing thiamine pyrophosphate or N-acetylcysteine mitigated the neurotoxicity. That a specific supplement reverses a specific toxicity is the strongest form of mechanistic evidence available short of a human trial.
Written into the record, not signed off as a reviewed claim
The safety assumption was that an intestinal antiseptic is not absorbed
In plain words
The drug was considered safe because it was supposed to act only inside the gut and not enter the body. It did enter the body.
What was measured
Not recorded
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
Clioquinol was marketed as a poorly absorbed intestinal agent, and much of its use — particularly in Japan for non-specific abdominal symptoms and diarrhoea — rested on the premise that a drug acting in the lumen carries no systemic risk. That premise licensed long courses, repeat courses and use for indications far broader than amoebiasis. It was wrong. The lipophilic metal chelates that clioquinol forms are precisely the species that cross membranes, so the chemistry that made it an antimicrobial is the chemistry that got it absorbed. A route-based safety argument is only as good as the absorption data behind it, and here there were essentially none.
Written into the record, not signed off as a reviewed claim
The same molecule was later trialled in Alzheimer's disease
In plain words
Thirty years after the ban, clioquinol was tested in a small Alzheimer's trial on the theory that its metal-gripping chemistry could break up amyloid plaques.
What was measured
Not recorded
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
A pilot phase 2 trial randomised 36 patients with moderately severe Alzheimer's disease to clioquinol or placebo, on the hypothesis that a metal-protein-attenuating compound inhibiting zinc and copper binding to amyloid beta would promote its dissolution. The treatment effect was significant in the more severely affected subgroup with baseline ADAS-cog of 25 or above, driven by substantial worsening in placebo patients against minimal deterioration on clioquinol. Plasma amyloid beta 42 fell on clioquinol and rose on placebo, and plasma zinc rose. The authors state the caveats of small sample size explicitly. That a compound withdrawn for neurotoxicity was reconsidered as a neuroprotective agent is not incoherent — the chelation is the same chemistry in both cases — but it does mean any efficacy signal has to be read against a well-documented mechanism of neuronal injury.
Written into the record, not signed off as a reviewed claim
A subgroup effect in 36 patients is a hypothesis, not a finding
In plain words
The Alzheimer's result came from part of a 36-person trial, and depended mostly on the placebo group getting worse rather than the treated group improving.
What was measured
That the pilot trial demonstrated clioquinol slows Alzheimer's disease
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The reported effect was confined to a subgroup defined by baseline severity within a randomised total of 36, and the authors attribute it to substantial worsening in placebo patients rather than to improvement on clioquinol. Both features — subgroup restriction and a control-arm-driven difference — mark a result as hypothesis-generating. The plasma amyloid beta 42 and zinc changes are genuine pharmacodynamic measurements showing the compound did what it was supposed to do biochemically. Whether that helps patients is the question the trial was too small to address, and the investigators say so. Reading this pilot as evidence that clioquinol treats Alzheimer's disease repeats, in miniature, the error that the aducanumab entry in this file records at scale.
Written into the record, not signed off as a reviewed claim
Fifty years to a mechanism, and the epidemiology never needed one
In plain words
The drug was banned in 1970 on population evidence alone. The biochemical explanation was still being worked out in the 2020s.
What was measured
Not recorded
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Reviews published in 2024 note that the underlying mechanisms of clioquinol toxicity had not been fully established, and the thiamine pyrophosphate work appeared in 2026. Related work has examined mitochondrial toxicity in neuroblastoma cells and the protective role of NQO1. So the ban preceded the mechanism by more than half a century. This is the correct order of operations and worth stating plainly: an epidemiological link strong enough to act on does not wait for a molecular explanation, and demanding one before acting would have cost thousands more cases. The mechanism, when it arrived, was consistent with the epidemiology rather than a correction to it.
Written into the record, not signed off as a reviewed claim
Where else this substance is registered
FDA substance identifier (UNII)
7BHQ856EJ5
CAS registry number
130-26-7
PubChem compound
2788
ChEMBL
CHEMBL497
ChEBI
74460
WHO international nonproprietary name list entry
2116
RxNorm concept
5942
EMA substance identifier
100000092134
European Chemicals Agency number
204-984-4
DrugBank
DB04815
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
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Trial roles classified for highlighted evidence
No registered study is classified as testing this substance.
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✓ Passed
Safety mode resolved
Suppression classes recorded: S8.
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Canonical metadata present
slug and display name present
What is missing or unclear◇Read 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.
Withdrawn in France; Germany; United Kingdom; Japan; United States; Zimbabwe; Bangladesh; Philippines; Saudi Arabia; Ethiopia; Honduras, 1973, for "neurotoxicity" (ChEMBL; Open Targets)
What the approval register records
1 approved application covers products containing this substance.
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What is not here
7 questions this page could not answer
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What was measured, goal by goal — found nothing in the sources checked.
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Felt, measured, or meaningful — found nothing in the sources checked.
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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 oral intestinal antiseptic epidemiologically linked in 1970 to subacute myelo-optic neuropathy — sensory and motor disturbance of the lower limbs with optic involvement, on a background of axonopathy of the spinal cord and optic nerves — and banned in Japan in September 1970, after which the epidemic ceased; the mechanism was still being characterised more than fifty years later, most recently as oxidative inactivation of thiamine pyrophosphate with consequent mitochondrial failure.
Recorded evidence blocks (5)
Q2
2 registered trials of Clioquinol — at which phases?
Approved in 1934, withdrawn in 1973: what happened to Clioquinol in France; Germany; United Kingdom; Japan; United States; Zimbabwe; Bangladesh; Philippines; Saudi Arabia; Ethiopia; Honduras?
Approved 1934, withdrawn 1973 in France; Germany; United Kingdom; Japan; United States; Zimbabwe; Bangladesh; Philippines; Saudi Arabia; Ethiopia; Honduras; the register's words: "neurotoxicity". Open Targets drug warning · CHEMBL497 · 2026-06-24
2 recorded reasons; France; Germany; United Kingdom; Japan; United States; Zimbabwe; Bangladesh; Philippines; Saudi Arabia; Ethiopia; Honduras
Show the evidence
Reason
"neurotoxicity"
"neurotoxicity"
recorded 2026-06-24 · last checked 2026-09-04
Q4
At the median, Clioquinol's trials enrolled 10.5 people — anything larger?
Median enrolment
10.5
Largest enrolment
11
Registered trials counted
2
Q5
What do 10 spontaneous reports say about Clioquinol — 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.
Clioquinol appears in spontaneous reports to regulators. Across the 10 most-reported reaction terms, 10 reaction mentions were counted: adjustment disorder with depressed mood 1; anti-cyclic citrullinated peptide antibody positive 1; breast cancer stage iii 1; c-reactive protein abnormal 1. FAERS via Open Targets · CHEMBL497 · 2026-06-24
Where do the label and the trials disagree about Clioquinol?
"neurotoxicity" against "approved": withdrawal status vs register status for Clioquinol.
OPEN_TARGETS_DRUG_WARNING, Health Canada DPD; 1 recorded pair
Show the evidence
OPEN_TARGETS_DRUG_WARNINGCHEMBL497
neurotoxicity; 2026-06-24
Health Canada DPD631
approved; 2026-09-04
Where it is registered
Where it’s registered
Withdrawn in France; Germany; United Kingdom; Japan; United States; Zimbabwe; Bangladesh; Philippines; Saudi Arabia; Ethiopia; Honduras, 1973, for "neurotoxicity" (ChEMBL; Open Targets)
ChEMBL 37 — CC BY-SA 3.0 Unported · ChEMBL ATC CC BY-SA · ClinicalTrials.gov — US Government work · Open Targets 26.06 — CC0 · mixed register set; per-register licences in docs/specs/corpus-20k-sources.md
✗ required summary fields resolved: 4 required field(s) not terminal: Why people use it, Best-supported result, Biggest unanswered question, Human evidence
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✓ source coverage passed: 5 source rows
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