What is Methylene Blue?
Methylene blue, also called methylthioninium chloride, is a synthetic phenothiazinium dye. First made in 1876, it formed the basis of early antimalarial chemotherapy and later led to the neuroleptic phenothiazines, and its ready oxidation and reduction underlies much of its activity (Wainwright and Crossley, 2002). It was the first synthetic antimalarial, used in the late 19th and early 20th centuries (Lu et al., 2018). Disguised Alpha supplies it as 10MG capsules, 60 per bottle, for laboratory research use only. Nothing on this page is guidance for use in people.
Methylene Blue reference data
| Property | Value |
|---|---|
| Name | Methylene blue |
| Also called | Methylthioninium chloride (INN, abbreviated MTC), C.I. Basic Blue 9, C.I. 52015, Swiss blue |
| Structure | 3,7-bis(dimethylamino)phenothiazin-5-ium chloride: the methylthioninium cation (C₁₆H₁₈N₃S⁺, 284.4 g/mol, PubChem CID 4139) with a chloride counterion |
| Compound class | Phenothiazinium (thiazine) dye; redox agent |
| Molecular formula | C₁₆H₁₈ClN₃S (anhydrous); C₁₆H₂₄ClN₃O₃S (trihydrate) |
| Molecular weight | 319.9 g/mol (anhydrous); 373.9 g/mol (trihydrate) |
| PubChem CID | 6099 |
| Form | Capsules, 10MG per capsule, 60 capsules per bottle (600MG per bottle) |
| Testing | Third-party tested, with the certificate for each lot published on the product page and in the COA portal |
Capsule format, strength and storage are from the Methylene Blue product page, which lists no formula or weight and does not say whether 10MG refers to the anhydrous salt or the trihydrate. Chemical data and synonyms are from PubChem CIDs 6099, 104827 and 4139.
See it beside the other compounds on this site in the peptide molecular weight reference table.
What the research covers
Published methylene blue research falls into six areas, and each summary below names its model. Mechanistic and neuroprotection data come from cells and rodents.
Methylene blue and mitochondria: redox cycling and electron transfer
Flavin enzymes use NAD(P)H to reduce methylene blue to leucomethylene blue, and cytochrome c reoxidizes it. In IMR90 human fibroblasts, nanomolar methylene blue delayed senescence by more than 20 population doublings and raised complex IV by 30 percent and oxygen consumption by 37 to 70 percent, which the authors tied to this cycling (Atamna et al., 2008).
In mitochondrial assays and HT-22 mouse hippocampal cells, it carried electrons from NADH to cytochrome c around blocked complexes I and III, while an N-acetylated derivative with its redox center disabled had no effect on complex activities (Wen et al., 2011). Models: cell lines and mitochondrial preparations.
Nitric oxide, guanylate cyclase and MAO-A
Methylene blue is widely used to block nitric oxide-stimulated guanylate cyclase. In blood vessels, endothelial cells and purified enzymes, it inhibited nitric oxide synthase directly, abolishing L-citrulline formation at 30 µM, while guanylate cyclase needed about 60 µM for half inhibition (Mayer et al., 1993). With purified human enzymes, it was a potent, tight-binding, reversible inhibitor of MAO-A and inhibited MAO-B only at much higher concentrations (Ramsay et al., 2007). Models: vascular tissue, endothelial cells and purified enzymes.
Neuroprotection and memory in rodents
In male Sprague-Dawley rats, methylene blue almost completely rescued rotenone-induced striatal dopamine depletion, attenuated nigral neuron loss and reduced damage after transient focal cerebral ischemia (Wen et al., 2011). Given locally with rotenone infused into the rat striatum, it shrank lesions and preserved cytochrome oxidase activity (Rojas et al., 2009).
Normal rats given 1 mg/kg after each holeboard training day made 66 percent of probe visits to baited holes versus 31 percent for saline controls, and in brain homogenates low but not high concentrations sped cytochrome c oxidation (Callaway et al., 2004). Models: rats; animal data only.
Tau aggregation and the hydromethylthionine trials
In a cell-free assay, methylene blue blocked tau-tau binding through the repeat domain, at higher concentrations than likely reachable clinically (Wischik et al., 1996). Phase 3 trials sponsored by the developer, TauRx, then tested LMTM, a stable reduced form of the methylthioninium moiety. In 891 people with mild to moderate Alzheimer's disease, two higher twice-daily amounts did not differ on either co-primary outcome from a low amount kept to mask urine discoloration (Gauthier et al., 2016).
In 800 people with mild disease, there was again no difference as randomized; revised analyses of nonrandomized monotherapy subgroups were significant, and the authors called for another randomized trial (Wilcock et al., 2018). In 598 amyloid-positive participants, hydromethylthionine mesylate (HMTM, the drug's current name) did not separate from a low methylthioninium chloride control on co-primary endpoints at 52 weeks, which the authors attributed to activity in the control arm (Wischik et al., 2026). Models: cell-free assay and human randomized trials.
Photodynamic and antimicrobial lab work
Methylene blue is a photosensitizer, and light-activated methylene blue and related dyes have been applied in antimicrobial work, especially the disinfection of blood products (Wainwright and Crossley, 2002). In Candida albicans strains that overexpress efflux pumps, ABC-type pumps cut methylene blue uptake and light-activated killing more than MFS-type pumps, and the ABC inhibitor verapamil raised both (Prates et al., 2011). Model: fungal cultures.
Adverse findings and regulatory status
A systematic review found 26 people with an acute confusional state after methylene blue infusion; 24 were on a serotonin reuptake inhibitor and one on clomipramine, and serotonin syndrome was a possible diagnosis in all 25 (Ng and Cameron, 2010). FDA's 2016 clinical review records two 2011 drug safety communications on serious central nervous system reactions when methylene blue in any formulation is given with serotonergic drugs.
The ProvayBlue label carries a boxed warning for serotonin syndrome with serotonergic drugs and opioids, notes that some reported cases were fatal, and contraindicates the drug in G6PD deficiency because of the risk of hemolytic anemia. A literature review lists methylene blue among seven medications with solid evidence for avoidance in G6PD deficiency (Youngster et al., 2010). The label also reports genotoxicity in bacterial and hamster cell tests and, in a two-year rat study, pancreatic islet adenomas or carcinomas in males. Models: case reports, reviews and FDA labeling.
Regulatory status (fda.gov, checked October 2026): the FDA approved ProvayBlue (methylene blue) injection in April 2016 for acquired methemoglobinemia. Drugs@FDA lists methylene blue only as intravenous solutions, brand and generic. No capsule or tablet is FDA-approved: the 2016 review called oral products containing it marketed but unapproved, and a 2020 FDA warning letter called methylene blue capsules sold with COVID-19 claims unapproved new drugs.
Key studies
- Mayer B, et al. "Inhibition of nitric oxide synthesis by methylene blue." Biochem Pharmacol. 1993. PMID 7679577. DOI 10.1016/0006-2952(93)90072-5. Vessels, endothelial cells and purified enzymes: direct nitric oxide synthase inhibition.
- Wischik CM, et al. "Selective inhibition of Alzheimer disease-like tau aggregation by phenothiazines." Proc Natl Acad Sci U S A. 1996. PMID 8855335. DOI 10.1073/pnas.93.20.11213. Cell-free assay: blocked tau-tau binding.
- Ramsay RR, et al. "Methylene blue and serotonin toxicity: inhibition of monoamine oxidase A (MAO A) confirms a theoretical prediction." Br J Pharmacol. 2007. PMID 17721552. DOI 10.1038/sj.bjp.0707430. Purified human enzymes: potent reversible MAO-A inhibition.
- Atamna H, et al. "Methylene blue delays cellular senescence and enhances key mitochondrial biochemical pathways." FASEB J. 2008. PMID 17928358. DOI 10.1096/fj.07-9610com. IMR90 human fibroblasts: delayed senescence, higher complex IV.
- Wen Y, et al. "Alternative mitochondrial electron transfer as a novel strategy for neuroprotection." J Biol Chem. 2011. PMID 21454572. DOI 10.1074/jbc.M110.208447. HT-22 cells and rats: electron bypass of complexes I and III.
- Gauthier S, et al. "Efficacy and safety of tau-aggregation inhibitor therapy in patients with mild or moderate Alzheimer's disease: a randomised, controlled, double-blind, parallel-arm, phase 3 trial." Lancet. 2016. PMID 27863809. DOI 10.1016/S0140-6736(16)31275-2. Randomized LMTM trial, 891 people: primary analysis negative.
Handling and storage of Methylene Blue capsules
- Store the sealed capsules at 15 to 25°C in the original container, away from moisture and direct light (storage guidance on the product page).
- Capsules ship in a sealed bottle or a resealable pouch, depending on the batch; close it fully after each opening.
- Methylene blue is an intense dye that stains skin, benches and glassware; wear gloves and use a dedicated weighing area.
- It is a photosensitizer, so protect solutions from light.
- Record the lot number and keep its certificate; use the measured content per capsule for quantitative work.
- For identity checks, compare against C₁₆H₁₈ClN₃S (319.9 g/mol, anhydrous); positive-ion mass spectrometry shows the methylthioninium cation near m/z 284.12.
Frequently asked questions
What is methylene blue?
A synthetic phenothiazinium dye, methylthioninium chloride, first made in 1876 and studied for its ready oxidation and reduction (Wainwright and Crossley, 2002).
Is methylthioninium chloride the same as methylene blue?
Yes. It is the International Nonproprietary Name for methylene blue (PubChem CID 6099), and trial papers abbreviate it MTC (Wischik et al., 2026).
How does methylene blue act on mitochondria?
In cell studies it serves as an alternative electron carrier from NADH to cytochrome c, bypassing blocked complexes I and III (Wen et al., 2011), and it raised complex IV activity and oxygen consumption in human fibroblasts (Atamna et al., 2008).
Is methylene blue FDA approved?
Only as a drug product: ProvayBlue (methylene blue) injection, approved in April 2016 for acquired methemoglobinemia, and generic versions. Drugs@FDA lists no capsule or tablet, and research capsules are not a drug product.
Why does methylene blue interact with serotonergic drugs?
It potently inhibits monoamine oxidase A (Ramsay et al., 2007), and case reports describe serotonin syndrome when it was given with serotonin reuptake inhibitors (Ng and Cameron, 2010). The approved drug's label carries a boxed warning for this.
Is LMTM the same as methylene blue?
No. LMTM, now called hydromethylthionine mesylate (HMTM), is a stabilized form of reduced methylthionine; methylthioninium chloride is the oxidized form (Wischik et al., 2026). Its three phase 3 trials showed no significant randomized difference on the main clinical outcomes, and Drugs@FDA lists no HMTM product.
Where can researchers buy methylene blue?
Disguised Alpha sells methylene blue for laboratory research as 10MG capsules, 60 per bottle, third-party tested with the certificate for each lot published on the product page: Methylene Blue.
Related compounds and guides
- NAD+ research guide
- SS-31 research guide
- MOTS-c research guide
- Glutathione research guide
- 5-Amino-1MQ research guide
- COA portal: every published certificate, by lot
This product is for research use only. It has not been evaluated for safety or effectiveness in humans. Not for human consumption. All products are intended for laboratory research purposes only.