Methylene blue
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Trade names | Urelene blue, Provayblue, Proveblue, others[1][2] |
Other names | CI 52015, basic blue 9[3] |
AHFS/Drugs.com | Monograph |
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By mouth, intravenous | |
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Pharmacokinetic data | |
Elimination half-life | 5 to 24 hours[6] |
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Methylthioninium chloride, commonly called methylene blue, is a salt used as a
Methylene blue is typically given by
Methylene blue was first prepared in 1876, by Heinrich Caro.[9] It is on the World Health Organization's List of Essential Medicines.[10]
Uses
Methemoglobinemia
Methylene blue is employed as a medication for the treatment of
Methylphen
Cyanide poisoning
Since its reduction potential is similar to that of oxygen and can be reduced by components of the electron transport chain, large doses of methylene blue are sometimes used as an antidote to potassium cyanide poisoning, a method first successfully tested in 1933 by Dr. Matilda Moldenhauer Brooks in San Francisco,[14] although first demonstrated by Bo Sahlin of Lund University, in 1926.[14][15]
Dye or stain
Methylene blue is used in
In surgeries such as
It is sometimes used in
A traditional application of methylene blue is the intravital or supravital staining of nerve fibers, an effect first described by Paul Ehrlich in 1887.[20] A dilute solution of the dye is either injected into tissue or applied to small freshly removed pieces. The selective blue coloration develops with exposure to air (oxygen) and can be fixed by immersion of the stained specimen in an aqueous solution of ammonium molybdate. Vital methylene blue was formerly much used for examining the innervation of muscle, skin and internal organs.[21][22][23] The mechanism of selective dye uptake is incompletely understood; vital staining of nerve fibers in skin is prevented by ouabain, a drug that inhibits the Na/K-ATPase of cell membranes.[24]
Placebo
Methylene blue has been used as a
Isobutyl nitrite toxicity
Isobutyl nitrite is one of the compounds used as poppers, an inhalant drug that induces a brief euphoria.
Isobutyl nitrite is known to cause methemoglobinemia.[27] Severe methemoglobinemia may be treated with methylene blue.[28]
Ifosfamide toxicity
Another use of methylene blue is to treat
Shock
It has also been used in septic shock and anaphylaxis.[33][34]
Methylene blue consistently increases blood pressure in people with vasoplegic syndrome (redistributive shock), but has not been shown to improve delivery of oxygen to tissues or to decrease mortality.[35][36][37][38]
Methylene blue has been used in calcium channel blocker toxicity as a rescue therapy for distributive shock unresponsive to first line agents. Evidence for its use in this circumstance is very poor and limited to a handful of case reports.[39][40][41][42][43][44][45][46][47][excessive citations]
Side effects
Cardiovascular[48][49] | Central Nervous System[48][49] | Dermatologic[48][49] | Gastrointestinal[48][49] | Genito-urinary[48][49] | Hematologic[48][49] |
---|---|---|---|---|---|
• Precordial pain
|
• Dizziness • Mental confusion • Headache • Fever |
• Staining of skin • Injection site necrosis (SC) |
• Fecal discoloration • Abdominal pain
|
• Discoloration of urine (doses over 80 µg) • Bladder irritation |
• Anemia |
Methylene blue is a
It causes
Chemistry
Methylene blue is a formal derivative of
Preparation
This compound is prepared by oxidation of 4-aminodimethylaniline in the presence of sodium thiosulfate to give the quinonediiminothiosulfonic acid, reaction with dimethylaniline, oxidation to the indamine, and cyclization to give the thiazine:[53]
A green electrochemical procedure, using only dimethyl-4-phenylenediamine and sulfide ions has been proposed.[54]
Light absorption properties
The maximum absorption of light is near 670 nm. The specifics of absorption depend on a number of factors, including
Species | Absorption peak | Extinction coefficient (dm3/mole·cm) |
---|---|---|
MB+ (solution) | 664 | 95000 |
MBH2+ (solution) | 741 | 76000 |
(MB+)2 (solution) | 605 | 132000 |
(MB+)3 (solution) | 580 | 110000 |
MB+ (adsorbed on clay) | 673 | 116000 |
MBH2+ (adsorbed on clay) | 763 | 86000 |
(MB+)2 (adsorbed on clay) | 596 | 80000 |
(MB+)3 (adsorbed on clay) | 570 | 114000 |
Other uses
Redox indicator
Methylene blue is widely used as a
Peroxide generator
Methylene blue is also a
Sulfide analysis
The formation of methylene blue after the reaction of
The addition of a strong
Test for milk freshness
Methylene blue is a dye behaving as a
Water testing
The adsorption of methylene blue serves as an indicator defining the adsorptive capacity of granular activated carbon in water filters. Adsorption of methylene blue is very similar to adsorption of pesticides from water, this quality makes methylene blue serve as a good predictor for filtration qualities of carbon. It is as well a quick method of comparing different batches of activated carbon of the same quality. A
The MBAS assay cannot distinguish between specific surfactants, however. Some examples of anionic surfactants are carboxylates, phosphates, sulfates, and sulfonates.[citation needed]
Methylene blue value of fine aggregate
The methylene blue value is defined as the number of milliliter's standard methylene value solution decolorized 0.1 g of activated carbon (dry basis).[64] Methylene blue value reflects the amount of clay minerals in aggregate samples.[65] In materials science, methylene blue solution is successively added to fine aggregate which is being agitated in water. The presence of free dye solution can be checked with stain test on a filter paper.[66]
Biological staining
In biology, methylene blue is used as a dye for a number of different staining procedures, such as Wright's stain and Jenner's stain. Since it is a temporary staining technique, methylene blue can also be used to examine RNA or DNA under the microscope or in a gel: as an example, a solution of methylene blue can be used to stain RNA on hybridization membranes in northern blotting to verify the amount of nucleic acid present. While methylene blue is not as sensitive as ethidium bromide, it is less toxic and it does not intercalate in nucleic acid chains, thus avoiding interference with nucleic acid retention on hybridization membranes or with the hybridization process itself.[citation needed]
It can also be used as an indicator to determine whether eukaryotic cells such as yeast are alive or dead. The methylene blue is reduced in viable cells, leaving them unstained. However dead cells are unable to reduce the oxidized methylene blue and the cells are stained blue. Methylene blue can interfere with the respiration of the yeast as it picks up hydrogen ions made during the process.[citation needed]
Aquaculture
Methylene blue is used in aquaculture and by tropical fish hobbyists as a treatment for fungal infections. It can also be effective in treating fish infected with ich although a combination of malachite green and formaldehyde is far more effective against the parasitic protozoa Ichthyophthirius multifiliis. It is usually used to protect newly laid fish eggs from being infected by fungus or bacteria. This is useful when the hobbyist wants to artificially hatch the fish eggs. Methylene blue is also very effective when used as part of a "medicated fish bath" for treatment of ammonia, nitrite, and cyanide poisoning as well as for topical and internal treatment of injured or sick fish as a "first response".[67]
History
Methylene blue has been described as "the first fully synthetic drug used in medicine." Methylene blue was first prepared in 1876 by German chemist Heinrich Caro.[68]
Its use in the treatment of malaria was pioneered by Paul Guttmann and Paul Ehrlich in 1891. During this period before the first World War, researchers like Ehrlich believed that drugs and dyes worked in the same way, by preferentially staining pathogens and possibly harming them. Changing the cell membrane of pathogens is in fact how various drugs work, so the theory was partially correct although far from complete. Methylene blue continued to be used in the second World War, where it was not well liked by soldiers, who observed, "Even at the loo, we see, we pee, navy blue." Antimalarial use of the drug has recently been revived.[69] It was discovered to be an antidote to carbon monoxide poisoning and cyanide poisoning in 1933 by Matilda Brooks.[70]
The blue urine was used to monitor psychiatric patients' compliance with medication regimes. This led to interest - from the 1890s to the present day - in the drug's
Names
The
Research
Malaria
Methylene blue was identified by Paul Ehrlich about 1891 as a possible treatment for malaria.[74] It disappeared as an anti-malarial during the Pacific War in the tropics, since American and Allied soldiers disliked its two prominent, but reversible side effects: turning the urine blue or green, and the sclera (the whites of the eyes) blue. Interest in its use as an anti-malarial has recently been revived,[71] especially due to its low price. Several clinical trials are in progress, trying to find a suitable drug combination. According to studies on children in Africa, it appears to have efficacy against malaria, but the attempts to combine methylene blue with chloroquine were disappointing.[75]
Alzheimer's
A Phase 3 clinical trial of LMTM (TauRx0237 or LMT-X), a derivative of methylene blue, failed to show any benefit against cognitive or functional decline in people with mild to moderate Alzheimer's disease. Disease progression for both the drug and the placebo were practically identical.[76][77]
Bipolar disorder
Methylene blue has been studied as an adjunctive medication in the treatment of bipolar disorder.[78]
Infectious diseases
It has been studied in AIDS-related Kaposi's sarcoma,[79] West Nile virus,[80] and to inactivate Staphylococcus aureus,[81] and HIV-1.[82] Phenothiazine dyes and light have been known to have virucidal properties for over 70 years.[83]
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External links
- "Methylene blue". Drug Information Portal. U.S. National Library of Medicine.
- "Methylene blue test". MedlinePlus.