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# Methylthioninium chloride (methylene blue)

A blue dye that turns methaemoglobin back into normal haemoglobin. It is avoided in G6PD deficiency and with serotonergic drugs.

Updated 2026-11-01

- Class: [Specific antidotes](https://durgical.com/en/pharmacology/classes/specific-antidotes/)
- Target: Methaemoglobin, through NADPH-dependent reduction
- ATC code: V03AB17
- WHO Model List of Essential Medicines

Also called: Methylene blue

## Mechanism of action

In methaemoglobinaemia the haem iron is oxidised to the ferric (Fe³⁺) state and cannot carry oxygen. Inside red cells, an NADPH-dependent reductase converts methylene blue to leucomethylene blue, which reduces the iron back to the ferrous (Fe²⁺) state. Because the pathway needs NADPH from the pentose phosphate pathway, it fails, and can cause haemolysis, in G6PD deficiency. Methylene blue is also a potent inhibitor of monoamine oxidase.

- An oxidant turns haem Fe²⁺ into Fe³⁺: methaemoglobin
- NADPH reductase turns methylene blue into leucomethylene blue
- Leucomethylene blue reduces Fe³⁺ back to Fe²⁺
- Haemoglobin carries oxygen again; cyanosis fades

## Pharmacokinetics

**Metabolism**
Mainly conjugated by UGT enzymes in the liver; minor cytochrome P450 metabolism

**Elimination**
In urine and stool, which turn blue-green

**Half-life**
About 24 hours

**Onset and duration**
The peak effect usually comes within 30 minutes

## Indications

- Symptomatic acquired methaemoglobinaemia, for example from sodium nitroprusside or benzocaine (including benzocaine used to adulterate street drugs) [Methemoglobinemia →](https://durgical.com/en/conditions/methemoglobinemia/)

## Adverse effects

### Common

- Blue-green urine and stools, bluish skin
- Headache
- Nausea, abdominal pain and diarrhoea
- Low potassium and magnesium
- Pain or irritation at the infusion site

### Serious (rare, important)

- Serotonin syndrome with SSRIs, SNRIs, MAO inhibitors or opioids
- Haemolytic anaemia, severe in G6PD deficiency
- Anaphylaxis
- Paradoxical methaemoglobinaemia at high doses

## Contraindications

- G6PD deficiency (risk of haemolysis, and the drug may not work)
- Severe hypersensitivity to methylene blue or other thiazine dyes

## Key interactions

**SSRIs, SNRIs, MAO inhibitors and opioids**
Serious or fatal serotonin syndrome, because methylene blue inhibits monoamine oxidase

**Pulse oximetry and blue-indicator urine tests**
The dye causes falsely low saturation readings and can distort dipstick results

## What is monitored

- Methaemoglobin level by co-oximetry on a blood gas sample
- Haemoglobin and signs of haemolysis
- Neurological status and signs of serotonin toxicity

## Administration and safety

- Slow intravenous infusion through a patent vein; never subcutaneously
- Diluted in 5% dextrose; sodium chloride is avoided because chloride reduces its solubility
- A second dose may follow after about an hour if methaemoglobinaemia persists; if two doses fail, other treatments are considered
- In Colombia it is registered as a diagnostic agent, not as an antidote, which can limit access

## Nursing care

- Ask about G6PD deficiency and serotonergic medicines before it is given
- Do not rely on pulse oximetry; use arterial co-oximetry
- Check the infusion site
- Tell the patient that urine and stools will turn blue-green

## Pregnancy and breastfeeding

It may cause fetal harm and is generally not recommended in pregnancy or breastfeeding unless the methaemoglobinaemia is life-threatening.

## Memory aid

Blue turns brown blood red: methylene blue fixes chocolate-brown methaemoglobin, but needs NADPH (so not in G6PD deficiency) and hates serotonergic company.

## Test yourself

Think of the answer, then tap the question to see it.

## How does methylene blue reduce methaemoglobin?

An NADPH-dependent reductase converts it to leucomethylene blue, which reduces Fe³⁺ back to Fe²⁺.

## Why is methylene blue contraindicated in G6PD deficiency?

These patients lack NADPH, so it may not work and can trigger haemolysis.

## Which drug combination with methylene blue can cause serotonin syndrome?

SSRIs, SNRIs, MAO inhibitors and opioids, because methylene blue inhibits monoamine oxidase.

## Why is pulse oximetry unreliable during treatment?

The blue dye interferes with the reading and underestimates saturation; co-oximetry is used.

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## Related drugs

- [Sodium nitrite](https://durgical.com/en/pharmacology/sodium-nitrite/)

## Related conditions

- [Methemoglobinemia](https://durgical.com/en/conditions/methemoglobinemia/)

[← Back to the class: Specific antidotes](https://durgical.com/en/pharmacology/classes/specific-antidotes/)

Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.

Sources: [DailyMed - METHYLENE BLUE injection](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=eec9bc86-b15b-4c0c-a669-65b03b73da0b) (DailyMed (U.S. National Library of Medicine), 2026); [Guía para el Manejo de Emergencias Toxicológicas](https://minsalud.gov.co/sites/rid/Lists/BibliotecaDigital/RIDE/DE/GT/guias-manejo-emergencias-toxicologicas-outpout.pdf) (Ministerio de Salud y Protección Social; Organización Panamericana de la Salud, 2017); [eEML - Electronic Essential Medicines List](https://list.essentialmeds.org/) (World Health Organization, 2025); [ATCDDD - ATC/DDD Index](https://atcddd.fhi.no/atc_ddd_index/?code=V03AB17) (WHO Collaborating Centre for Drug Statistics Methodology, 2026).

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Representative model, for educational purposes only.

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Source: https://durgical.com/en/pharmacology/methylthioninium-chloride/
License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/pharmacology/methylthioninium-chloride/
