Methylthioninium chloride, commonly called methylene blue, is a salt used as a dye and as a medication. Methylene blue is a thiazine dye. As a medication, it is mainly used to treat methemoglobinemia by converting the ferric iron in

hemoglobin Hemoglobin (haemoglobin BrE) (from the Greek word αἷμα, ''haîma'' 'blood' + Latin ''globus'' 'ball, sphere' + ''-in'') (), abbreviated Hb or Hgb, is the iron-containing oxygen-transport metalloprotein present in red blood cells (erythrocyt ...

ferrous iron In chemistry, iron(II) refers to the element iron in its +2 oxidation state. In ionic compounds (salts), such an atom may occur as a separate cation (positive ion) denoted by Fe2+. The adjective ferrous or the prefix ferro- is often used to ...

. Specifically, it is used to treat methemoglobin levels that are greater than 30% or in which there are symptoms despite oxygen therapy. It has previously been used for treating

cyanide poisoning Cyanide poisoning is poisoning that results from exposure to any of a number of forms of cyanide. Early symptoms include headache, dizziness, fast heart rate, shortness of breath, and vomiting. This phase may then be followed by seizures, sl ...

and

urinary tract infections A urinary tract infection (UTI) is an infection that affects part of the urinary tract. When it affects the lower urinary tract it is known as a bladder infection (cystitis) and when it affects the upper urinary tract it is known as a kidne ...

, but this use is no longer recommended. Methylene blue is typically given by

injection into a vein Intravenous therapy (abbreviated as IV therapy) is a medical technique that administers fluids, medications and nutrients directly into a person's vein. The intravenous route of administration is commonly used for rehydration or to provide nutri ...

. Common side effects include headache, vomiting, confusion, shortness of breath, and high blood pressure. Other side effects include

serotonin syndrome Serotonin syndrome (SS) is a group of symptoms that may occur with the use of certain serotonergic medications or drugs. The degree of symptoms can range from mild to severe, including a potentiality of death. Symptoms in mild cases include high ...

, red blood cell breakdown, and

allergic reactions Allergies, also known as allergic diseases, refer a number of conditions caused by the hypersensitivity of the immune system to typically harmless substances in the environment. These diseases include hay fever, food allergies, atopic derm ...

. Use often turns the urine, sweat, and stool blue to green in color. While use during

pregnancy Pregnancy is the time during which one or more offspring develops (gestation, gestates) inside a woman, woman's uterus (womb). A multiple birth, multiple pregnancy involves more than one offspring, such as with twins. Pregnancy usually occur ...

may harm the baby, not using it in methemoglobinemia is likely more dangerous. Methylene blue was first prepared in 1876, by

Heinrich Caro Heinrich Caro (February 13, 1834 in Posen, Prussia Germany now Poznań, Poland – September 11, 1910 in Dresden), was a German chemist. He was a Sephardic Jew. He started his study of chemistry at the Friedrich Wilhelms University and later ...

. It is on the

World Health Organization's List of Essential Medicines The WHO Model List of Essential Medicines (aka Essential Medicines List or EML), published by the World Health Organization (WHO), contains the medications considered to be most effective and safe to meet the most important needs in a health s ...

Medical uses

Methemoglobinemia

Methylene blue is employed as a medication for the treatment of methemoglobinemia, which can arise from ingestion of certain pharmaceuticals, toxins, or

broad beans ''Vicia faba'', commonly known as the broad bean, fava bean, or faba bean, is a species of vetch, a flowering plant in the pea and bean family Fabaceae. It is widely cultivated as a crop for human consumption, and also as a cover crop. Var ...

. Normally, through the

NADH Nicotinamide adenine dinucleotide (NAD) is a coenzyme central to metabolism. Found in all living cells, NAD is called a dinucleotide because it consists of two nucleotides joined through their phosphate groups. One nucleotide contains an aden ...

or NADPH dependent methemoglobin reductase enzymes, methemoglobin is reduced back to hemoglobin. When large amounts of methemoglobin occur secondary to toxins, methemoglobin reductases are overwhelmed. Methylene blue, when injected intravenously as an antidote, is itself first reduced to leucomethylene blue, which then reduces the

heme Heme, or haem (pronounced / hi:m/ ), is a precursor to hemoglobin, which is necessary to bind oxygen in the bloodstream. Heme is biosynthesized in both the bone marrow and the liver. In biochemical terms, heme is a coordination complex "consis ...

group from

methemoglobin Methemoglobin (British: methaemoglobin) (pronounced "met-hemoglobin") is a hemoglobin ''in the form of metalloprotein'', in which the iron in the heme group is in the Fe3+ (ferric) state, not the Fe2+ (ferrous) of normal hemoglobin. Sometimes, it i ...

. Methylene blue can reduce the half life of methemoglobin from hours to minutes. At high doses, however, methylene blue actually induces methemoglobinemia, reversing this pathway.

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 Matilda Moldenhauer Brooks (1888–1981) was a cellular biologist best known for her 1932 discovery that the staining compound methylene blue is an antidote to carbon monoxide and cyanide poisoning. She held a PhD in zoology and spent her prof ...

in San Francisco, although first demonstrated by Bo Sahlin of

Lund University , motto = Ad utrumque , mottoeng = Prepared for both , established = , type = Public research university , budget = SEK 9 billion

Dye or stain

Methylene blue is used in

endoscopic An endoscopy is a procedure used in medicine to look inside the body. The endoscopy procedure uses an endoscope to examine the interior of a hollow organ or cavity of the body. Unlike many other medical imaging techniques, endoscopes are insert ...

polypectomy as an adjunct to saline or epinephrine, and is used for injection into the submucosa around the polyp to be removed. This allows the submucosal tissue plane to be identified after the polyp is removed, which is useful in determining if more tissue needs to be removed, or if there has been a high risk for perforation. Methylene blue is also used as a dye in chromoendoscopy, and is sprayed onto the mucosa of the gastrointestinal tract in order to identify

dysplasia Dysplasia is any of various types of abnormal growth or development of cells (microscopic scale) or organs ( macroscopic scale), and the abnormal histology or anatomical structure(s) resulting from such growth. Dysplasias on a mainly microscopi ...

, or pre-cancerous lesions. Intravenously injected methylene blue is readily released into the urine and thus can be used to test the

urinary tract The urinary system, also known as the urinary tract or renal system, consists of the kidneys, ureters, bladder, and the urethra. The purpose of the urinary system is to eliminate waste from the body, regulate blood volume and blood pressure, c ...

for leaks or

fistula A fistula (plural: fistulas or fistulae ; from Latin ''fistula'', "tube, pipe") in anatomy is an abnormal connection between two hollow spaces (technically, two epithelialized surfaces), such as blood vessels, intestines, or other hollow or ...

s. In surgeries such as

sentinel lymph node The sentinel lymph node is the hypothetical first lymph node or group of nodes draining a cancer. In case of established cancerous dissemination it is postulated that the sentinel lymph nodes are the target organs primarily reached by metastasiz ...

dissections, methylene blue can be used to visually trace the lymphatic drainage of tested tissues. Similarly, methylene blue is added to

bone cement Bone cements have been used very successfully to anchor artificial joints (hip joints, knee joints, shoulder and elbow joints) for more than half a century. Artificial joints (referred to as prostheses) are anchored with bone cement. The bone ce ...

in orthopedic operations to provide easy discrimination between native bone and cement. Additionally, methylene blue accelerates the hardening of bone cement, increasing the speed at which bone cement can be effectively applied. Methylene blue is used as an aid to visualisation/orientation in a number of medical devices, including a Surgical sealant film, TissuePatch. In

s and

pilonidal sinus Pilonidal disease is a type of skin infection which typically occurs as a cyst Intergluteal cleft, between the cheeks of the buttocks and often at the upper end. Symptoms may include pain, swelling, and redness. There may also be drainage of flui ...

es it is used to identify the tract for complete excision. It can also be used during gastrointestinal surgeries (such as bowel resection or

gastric bypass Gastric bypass surgery refers to a technique in which the stomach is divided into a small upper pouch and a much larger lower "remnant" pouch and then the small intestine is rearranged to connect to both. Surgeons have developed several differ ...

) to test for leaks. It is sometimes used in

cytopathology Cytopathology (from Greek , ''kytos'', "a hollow"; , ''pathos'', "fate, harm"; and , '' -logia'') is a branch of pathology that studies and diagnoses diseases on the cellular level. The discipline was founded by George Nicolas Papanicolaou in ...

, in mixtures including Wright-Giemsa and

Diff-Quik Diff-Quik is a commercial Romanowsky stain variant used to rapidly stain and differentiate a variety of pathology specimens. It is most frequently used for blood films and cytopathological smears, including fine needle aspirates. The Diff-Quik pr ...

. It confers a blue color to both nuclei and cytoplasm, and makes the nuclei more visible. When methylene blue is "polychromed" (oxidized in solution or "ripened" by fungal metabolism, as originally noted in the thesis of Dr. D. L. Romanowsky in the 1890s), it gets serially demethylated and forms all the tri-, di-, mono- and non-methyl intermediates, which are

Azure B Azure may refer to: Colour * Azure (color), a hue of blue ** Azure (heraldry) ** Shades of azure, shades and variations Arts and media * ''Azure'' (Art Farmer and Fritz Pauer album), 1987 * Azure (Gary Peacock and Marilyn Crispell album), 2013 ...

Azure A Azure A is an organic compound with the chemical formula C14H14ClN3S. It is a light blue to dark blue dye. It is used as a screening test for mucopolysaccharides. It can also be used to stain lysosome in blood smears, and is often used in Giemsa ...

, Azure C, and

thionine Thionine, also known as Lauth's violet, is the salt of a heterocyclic compound. It was firstly synthesised by Charles Lauth. A variety of salts are known including the chloride and acetate, called respectively thionine chloride and thionine ac ...

, respectively. This is the basis of the basophilic part of the spectrum of Romanowski-Giemsa effect. If only synthetic Azure B and

Eosin Y Eosin Y, also called C.I. 45380 or C.I. Acid Red 87, is a member of the triarylmethane dyes. It is produced from fluorescein by bromination. Use Eosin Y is commonly used as the red dye in red inks. It is commonly used in histology, most nota ...

is used, it may serve as a standardized

Giemsa stain Giemsa stain (), named after German chemist and bacteriologist Gustav Giemsa, is a nucleic acid stain used in cytogenetics and for the histopathological diagnosis of malaria and other parasites. Uses It is specific for the phosphate groups of ...

; but, without methylene blue, the normal neutrophilic granules tend to overstain and look like toxic granules. On the other hand, if methylene blue is used it might help to give the normal look of neutrophil granules and may also enhance the staining of nucleoli and polychromatophilic RBCs (reticulocytes). A traditional application of methylene blue is the intravital or supravital staining of nerve fibers, an effect first described by

Paul Ehrlich Paul Ehrlich (; 14 March 1854 – 20 August 1915) was a Nobel Prize-winning German physician and scientist who worked in the fields of hematology, immunology, and antimicrobial chemotherapy. Among his foremost achievements were finding a cure ...

in 1887. 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. 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.

Placebo

Methylene blue has been used as a

placebo A placebo ( ) is a substance or treatment which is designed to have no therapeutic value. Common placebos include inert tablets (like sugar pills), inert injections (like saline), sham surgery, and other procedures. In general, placebos can af ...

; physicians would tell their patients to expect their urine to change color and view this as a sign that their condition had improved. This same side effect makes methylene blue difficult to use in traditional placebo-controlled

clinical studies Clinical trials are prospective biomedical or behavioral research studies on human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel vaccines, drugs, dieta ...

, including those testing for its efficacy as a treatment.

Isobutyl nitrite toxicity

Isobutyl nitrite is one of the compounds used as

poppers Popper is a slang term given broadly to drugs of the chemical class called alkyl nitrites that are inhaled. Most widely sold products include the original isoamyl nitrite or isopentyl nitrite, and isopropyl nitrite. Isobutyl nitrite is al ...

, an

inhalant Inhalants are a broad range of household and industrial chemicals whose volatile vapors or pressurized gases can be concentrated and breathed in via the nose or mouth to produce intoxication, in a manner not intended by the manufacturer. They ...

drug that induces a brief euphoria.

Isobutyl nitrite Isobutyl nitrite, C4H9NO2, is an alkyl nitrite, an ester of isobutanol and nitrous acid. Its chemical structure is ( CH3)2CH- CH2-ONO. Isobutyl nitrite is a pungent colorless liquid. It acts as a vasodilator, and is used as an inhalant recreat ...

is known to cause methemoglobinemia. Severe methemoglobinemia may be treated with methylene blue.

Ifosfamide toxicity

Another use of methylene blue is to treat

ifosfamide Ifosfamide (IFO), sold under the brand name Ifex among others, is a chemotherapy medication used to treat a number of types of cancer. This includes testicular cancer, soft tissue sarcoma, osteosarcoma, bladder cancer, small cell lung cancer, ...

neurotoxicity. Methylene blue was first reported for treatment and

prophylaxis Preventive healthcare, or prophylaxis, consists of measures taken for the purposes of disease prevention.Hugh R. Leavell and E. Gurney Clark as "the science and art of preventing disease, prolonging life, and promoting physical and mental hea ...

of ifosfamide neuropsychiatric toxicity in 1994. A toxic metabolite of ifosfamide,

chloroacetaldehyde Chloroacetaldehyde is an organic compound with the formula ClCH2CHO. Like some related compounds, it is highly electrophilic reagent and a potentially dangerous alkylating agent. The compound is not normally encountered in the anhydrous form, bu ...

(CAA), disrupts the mitochondrial

respiratory chain An electron transport chain (ETC) is a series of protein complexes and other molecules that transfer electrons from electron donors to electron acceptors via redox reactions (both reduction and oxidation occurring simultaneously) and couples thi ...

, leading to an accumulation of nicotinamide adenine dinucleotide hydrogen (NADH). Methylene blue acts as an alternative electron acceptor, and reverses the NADH inhibition of hepatic gluconeogenesis while also inhibiting the transformation of chloroethylamine into chloroacetaldehyde, and inhibits multiple amine oxidase activities, preventing the formation of CAA. The dosing of methylene blue for treatment of ifosfamide neurotoxicity varies, depending upon its use simultaneously as an adjuvant in ifosfamide infusion, versus its use to reverse psychiatric symptoms that manifest after completion of an ifosfamide infusion. Reports suggest that methylene blue up to six doses a day have resulted in improvement of symptoms within 10 minutes to several days. Alternatively, it has been suggested that intravenous methylene blue every six hours for prophylaxis during ifosfamide treatment in people with history of ifosfamide neuropsychiatric toxicity. Prophylactic administration of methylene blue the day before initiation of ifosfamide, and three times daily during ifosfamide chemotherapy has been recommended to lower the occurrence of ifosfamide neurotoxicity.

Shock

Gross pathology of normal brain and brain of patient treated with methylene blue before death

It has also been used in septic shock and

anaphylaxis Anaphylaxis is a serious, potentially fatal allergic reaction and medical emergency that is rapid in onset and requires immediate medical attention regardless of use of emergency medication on site. It typically causes more than one of the foll ...

. Methylene blue consistently increases blood pressure in people with

vasoplegic syndrome Vasoplegic syndrome (VPS) is a postperfusion syndrome characterized by low systemic vascular resistance and a high cardiac output. Causes VPS occurs more frequently after on pump CABG surgery versus off pump CABG surgery. Hypothermia during sur ...

(redistributive shock), but has not been shown to improve delivery of oxygen to tissues or to decrease mortality. 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.

Side effects

Methylene blue is a monoamine oxidase inhibitor (MAOI), and if infused intravenously at doses exceeding 5 mg/kg, may precipitate serious serotonin toxicity,

, if combined with any

selective serotonin reuptake inhibitors Selective serotonin reuptake inhibitors (SSRIs) are a class of drugs that are typically used as antidepressants in the treatment of major depressive disorder, anxiety disorders, and other psychological conditions. SSRIs increase the extracellul ...

(SSRIs) or other serotonin reuptake inhibitor (e.g.,

duloxetine Duloxetine, sold under the brand name Cymbalta among others, is a medication used to treat major depressive disorder, generalized anxiety disorder, fibromyalgia, neuropathic pain and central sensitization. It is taken by mouth. It is a seroton ...

sibutramine Sibutramine, formerly sold under the brand name Meridia among others, is an appetite suppressant which has been discontinued in many countries. It works as a serotonin–norepinephrine reuptake inhibitor similar to a tricyclic antidepressant. Un ...

venlafaxine Venlafaxine, sold under the brand name Effexor among others, is an antidepressant medication of the serotonin-norepinephrine reuptake inhibitor (SNRI) class. It is used to treat major depressive disorder, generalized anxiety disorder, panic ...

clomipramine Clomipramine, sold under the brand name Anafranil among others, is a tricyclic antidepressant (TCA). It is used for the treatment of obsessive–compulsive disorder, panic disorder, major depressive disorder, and chronic pain. It may increase th ...

imipramine Imipramine, sold under the brand name Tofranil, among others, is a tricyclic antidepressant (TCA) mainly used in the treatment of depression. It is also effective in treating anxiety and panic disorder. The drug is also used to treat bedwetting. ...

). It causes

hemolytic anemia Hemolytic anemia or haemolytic anaemia is a form of anemia due to hemolysis, the abnormal breakdown of red blood cells (RBCs), either in the blood vessels (intravascular hemolysis) or elsewhere in the human body (extravascular). This most commonly ...

in carriers of the

G6PD Glucose-6-phosphate dehydrogenase (G6PD or G6PDH) () is a cytosolic enzyme that catalyzes the chemical reaction : D-glucose 6-phosphate + NADP+ + H2O 6-phospho-D-glucono-1,5-lactone + NADPH + H+ This enzyme participates in the pentose phosp ...

(

favism Glucose-6-phosphate dehydrogenase deficiency (G6PDD), which is the most common enzyme deficiency worldwide, is an inborn error of metabolism that predisposes to red blood cell breakdown. Most of the time, those who are affected have no symptoms. ...

) enzymatic deficiency.

Chemistry

Methylene blue is a formal derivative of

phenothiazine Phenothiazine, abbreviated PTZ, is an organic compound that has the formula S(C6H4)2NH and is related to the thiazine-class of heterocyclic compounds. Derivatives of phenothiazine are highly bioactive and have widespread use and rich history. T ...

. It is a dark green powder that yields a blue solution in

water Water (chemical formula ) is an Inorganic compound, inorganic, transparent, tasteless, odorless, and Color of water, nearly colorless chemical substance, which is the main constituent of Earth's hydrosphere and the fluids of all known living ...

. The hydrated form has 3 molecules of water per unit of methylene blue. Methylene blue has a pH of 6 in water(10g/L) at 25 °C (77 °F).

Preparation

This compound is prepared by oxidation of dimethyl-4-phenylenediamine in the presence of

sodium thiosulfate Sodium thiosulfate (sodium thiosulphate) is an inorganic compound with the formula . Typically it is available as the white or colorless pentahydrate, . The solid is an efflorescent (loses water readily) crystalline substance that dissolves well in ...

: :

Light absorption properties

The maximum absorption of light is near 670 nm. The specifics of absorption depend on a number of factors, including

protonation In chemistry, protonation (or hydronation) is the adding of a proton (or hydron, or hydrogen cation), (H+) to an atom, molecule, or ion, forming a conjugate acid. (The complementary process, when a proton is removed from a Brønsted–Lowry acid ...

adsorption Adsorption is the adhesion of atoms, ions or molecules from a gas, liquid or dissolved solid to a surface. This process creates a film of the ''adsorbate'' on the surface of the ''adsorbent''. This process differs from absorption, in which ...

to other materials, and

metachromasy Metachromasia (var. metachromasy) is a characteristical change in the color of staining carried out in biological tissues, exhibited by certain dyes when they bind to particular substances present in these tissues, called chromotropes. For example ...

- the formation of dimers and higher-order aggregates depending on concentration and other interactions:

Other uses

Reflections in a flask of Methylene Blue

Redox indicator

Methylene blue is widely used as a

redox indicator A redox indicator (also called an oxidation-reduction indicator) is an indicator which undergoes a definite color change at a specific electrode potential. The requirement for fast and reversible color change means that the oxidation-reduction e ...

analytical chemistry Analytical chemistry studies and uses instruments and methods to separate, identify, and quantify matter. In practice, separation, identification or quantification may constitute the entire analysis or be combined with another method. Separati ...

. Solutions of this substance are blue when in an oxidizing environment, but will turn colorless if exposed to a reducing agent. The redox properties can be seen in a classical demonstration of

chemical kinetics Chemical kinetics, also known as reaction kinetics, is the branch of physical chemistry that is concerned with understanding the rates of chemical reactions. It is to be contrasted with chemical thermodynamics, which deals with the direction in ...

in general chemistry, the " blue bottle" experiment. Typically, a solution is made of

glucose Glucose is a simple sugar with the molecular formula . Glucose is overall the most abundant monosaccharide, a subcategory of carbohydrates. Glucose is mainly made by plants and most algae during photosynthesis from water and carbon dioxide, u ...

(dextrose), methylene blue, and sodium hydroxide. Upon shaking the bottle,

oxygen Oxygen is the chemical element with the symbol O and atomic number 8. It is a member of the chalcogen group in the periodic table, a highly reactive nonmetal, and an oxidizing agent that readily forms oxides with most elements as ...

oxidizes methylene blue, and the solution turns blue. The dextrose will gradually reduce the methylene blue to its colorless, reduced form. Hence, when the dissolved dextrose is entirely consumed, the solution will turn blue again. The redox midpoint potential E' is +0.01 V.

Peroxide generator

Methylene blue is also a

photosensitizer Photosensitizers produce a physicochemical change in a neighboring molecule by either donating an electron to the substrate or by abstracting a hydrogen atom from the substrate. At the end of this process, the photosensitizer eventually returns t ...

used to create singlet oxygen when exposed to both oxygen and light. It is used in this regard to make organic

peroxides In chemistry, peroxides are a group of compounds with the structure , where R = any element. The group in a peroxide is called the peroxide group or peroxo group. The nomenclature is somewhat variable. The most common peroxide is hydrogen p ...

by a Diels-Alder reaction which is spin forbidden with normal atmospheric

triplet oxygen Triplet oxygen, 3O2, refers to the ''S'' = 1 electronic ground state of molecular oxygen (dioxygen). It is the most stable and common allotrope of oxygen. Molecules of triplet oxygen contain two unpaired electrons, making triplet oxygen an unus ...

Sulfide analysis

The formation of methylene blue after the reaction of hydrogen sulfide with dimethyl-p-phenylenediamine and

iron(III) In chemistry, iron(III) refers to the element iron in its +3 oxidation state. In ionic compounds (salts), such an atom may occur as a separate cation (positive ion) denoted by Fe3+. The adjective ferric or the prefix ferri- is often used to sp ...

at pH 0.4 – 0.7 is used to determine by photometric measurements sulfide concentration in the range 0.020 to 1.50 mg/L (20 ppb to 1.5 ppm). The test is very sensitive and the blue coloration developing upon contact of the reagents with dissolved H₂S is stable for 60 min. Ready-to-use kits such as the ''Spectroquant'' sulfide test facilitate routine analyses. The methylene blue sulfide test is a convenient method often used in soil microbiology to quickly detect in water the metabolic activity of

sulfate reducing bacteria Sulfate-reducing microorganisms (SRM) or sulfate-reducing prokaryotes (SRP) are a group composed of sulfate-reducing bacteria (SRB) and sulfate-reducing archaea (SRA), both of which can perform anaerobic respiration utilizing sulfate () as termina ...

(SRB). It should be observed that in this test, methylene blue is a product of reaction and not a reagent. The addition of a strong

reducing agent In chemistry, a reducing agent (also known as a reductant, reducer, or electron donor) is a chemical species that "donates" an electron to an (called the , , , or ). Examples of substances that are commonly reducing agents include the Earth me ...

, such as ascorbic acid, to a sulfide-containing solution is sometimes used to prevent sulfide oxidation from atmospheric oxygen. Although it is certainly a sound precaution for the determination of sulfide with an

ion selective electrode An ion-selective electrode (ISE), also known as a specific ion electrode (SIE), is a transducer (or sensor) that converts the activity of a specific ion dissolved in a solution into an electrical potential. The voltage is theoretically dependent ...

, it might however hamper the development of the blue color if the freshly formed methylene blue is also reduced, as described here above in the paragraph on redox indicator.

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

color reaction In chemistry, a color reaction or colour reaction is a chemical reaction that is used to transform colorless chemical compounds into colored derivatives which can be detected visually or with the aid of a colorimeter. The concentration of a color ...

in an acidified, aqueous methylene blue solution containing chloroform can detect

anionic surfactant Surfactants are chemical compounds that decrease the surface tension between two liquids, between a gas and a liquid, or interfacial tension between a liquid and a solid. Surfactants may act as detergents, wetting agents, emulsifiers, foaming ...

s in a water sample. Such a test is known as an MBAS assay (methylene blue active substances assay). The MBAS assay cannot distinguish between specific surfactants, however. Some examples of anionic surfactants are

carboxylate In organic chemistry, a carboxylate is the conjugate base of a carboxylic acid, (or ). It is an ion with negative charge. Carboxylate salts are salts that have the general formula , where M is a metal and ''n'' is 1, 2,...; ''carboxylat ...

phosphate In chemistry, a phosphate is an anion, salt, functional group or ester derived from a phosphoric acid. It most commonly means orthophosphate, a derivative of orthophosphoric acid . The phosphate or orthophosphate ion is derived from phosph ...

sulfate The sulfate or sulphate ion is a polyatomic anion with the empirical formula . Salts, acid derivatives, and peroxides of sulfate are widely used in industry. Sulfates occur widely in everyday life. Sulfates are salts of sulfuric acid and many ...

s, and

sulfonate In organosulfur chemistry, a sulfonate is a salt or ester of a sulfonic acid. It contains the functional group , where R is an organic group. Sulfonates are the conjugate bases of sulfonic acids. Sulfonates are generally stable in water, non-o ...

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). Methylene blue value reflects the amount of clay minerals in aggregate samples. 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.

Biological staining

In biology, methylene blue is used as a dye for a number of different staining procedures, such as

Wright's stain Wright's stain is a hematologic stain that facilitates the differentiation of blood cell types. It is classically a mixture of eosin (red) and methylene blue dyes. It is used primarily to stain peripheral blood smears, urine samples, and bone m ...

and

Jenner's stain Jenner's stain (methylene blue eosinate) is used in microscopy for staining blood smear A blood smear, peripheral blood smear or blood film is a thin layer of blood smeared on a glass microscope slide and then stained in such a way as to allo ...

. Since it is a temporary staining technique, methylene blue can also be used to examine RNA or DNA under the

microscope A microscope () is a laboratory instrument used to examine objects that are too small to be seen by the naked eye. Microscopy is the science of investigating small objects and structures using a microscope. Microscopic means being invisi ...

or in a gel: as an example, a solution of methylene blue can be used to stain RNA on hybridization membranes in

northern blot The northern blot, or RNA blot,Gilbert, S. F. (2000) Developmental Biology, 6th Ed. Sunderland MA, Sinauer Associates. is a technique used in molecular biology research to study gene expression by detection of RNA (or isolated mRNA) in a sample ...

ting to verify the amount of nucleic acid present. While methylene blue is not as sensitive as

ethidium bromide Ethidium bromide (or homidium bromide, chloride salt homidium chloride) is an intercalating agent commonly used as a fluorescent tag ( nucleic acid stain) in molecular biology laboratories for techniques such as agarose gel electrophoresis. It ...

, it is less toxic and it does not

intercalate Intercalation may refer to: *Intercalation (chemistry), insertion of a molecule (or ion) into layered solids such as graphite * Intercalation (timekeeping), insertion of a leap day, week or month into some calendar years to make the calendar foll ...

in nucleic acid chains, thus avoiding interference with nucleic acid retention on hybridization membranes or with the hybridization process itself. 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.

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 Malachite green is an organic compound that is used as a dyestuff and controversially as an antimicrobial in aquaculture. Malachite green is traditionally used as a dye for materials such as silk, leather, and paper. Despite its name the dye is ...

and

formaldehyde Formaldehyde ( , ) (systematic name methanal) is a naturally occurring organic compound with the formula and structure . The pure compound is a pungent, colourless gas that polymerises spontaneously into paraformaldehyde (refer to section ...

is far more effective against the parasitic protozoa ''

Ichthyophthirius multifiliis ''Ichthyophthirius multifiliis'', often termed "Ich", is a parasitic ciliate described by the French parasitologist Fouquet in 1876. Only one species is found in the genus which also gave name to the family. The name literally translates as "the ...

''. 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".

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

. Its use in the treatment of malaria was pioneered by Paul Guttmann and

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 The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment ( ...

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. It was discovered to be an antidote to

carbon monoxide poisoning Carbon monoxide poisoning typically occurs from breathing in carbon monoxide (CO) at excessive levels. Symptoms are often described as " flu-like" and commonly include headache, dizziness, weakness, vomiting, chest pain, and confusion. Large ...

and

in 1933 by Matilda Brooks. 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 antidepressant and other

psychotropic A psychoactive drug, psychopharmaceutical, psychoactive agent or psychotropic drug is a chemical substance, that changes functions of the nervous system, and results in alterations in perception, mood, consciousness, cognition or behavior. Th ...

effects. It became the

lead compound A lead compound (, i.e. a "leading" compound, not to be confused with various compounds of the metallic element lead) in drug discovery is a chemical compound that has pharmacology, pharmacological or biological activity likely to be therapeutical ...

in research leading to the discovery of

chlorpromazine Chlorpromazine (CPZ), marketed under the brand names Thorazine and Largactil among others, is an antipsychotic medication. It is primarily used to treat psychotic disorders such as schizophrenia. Other uses include the treatment of bipolar di ...

Names

The International Nonproprietary Name (INN) of methylene blue is methylthioninium chloride.

Research

Malaria

Methylene blue was identified by

about 1891 as a possible treatment for

malaria Malaria is a mosquito-borne infectious disease that affects humans and other animals. Malaria causes symptoms that typically include fever, tiredness, vomiting, and headaches. In severe cases, it can cause jaundice, seizures, coma, or death. S ...

. 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 Urine is a liquid by-product of metabolism in humans and in many other animals. Urine flows from the kidneys through the ureters to the urinary bladder. Urination results in urine being excreted from the body through the urethra. Cellular ...

blue or green, and the sclera (the whites of the eyes) blue. Interest in its use as an anti-malarial has recently been revived, 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 Chloroquine is a medication primarily used to prevent and treat malaria in areas where malaria remains sensitive to its effects. Certain types of malaria, resistant strains, and complicated cases typically require different or additional medi ...

were disappointing.

Alzheimer's

A Phase 3 clinical trial of LMTM (TauRx0237 or LMT-X), a

derivative In mathematics, the derivative of a function of a real variable measures the sensitivity to change of the function value (output value) with respect to a change in its argument (input value). Derivatives are a fundamental tool of calculus. ...

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.

Bipolar disorder

Methylene blue has been studied as an adjunctive medication in the treatment of

bipolar disorder Bipolar disorder, previously known as manic depression, is a mental disorder characterized by periods of depression and periods of abnormally elevated mood that last from days to weeks each. If the elevated mood is severe or associated with ...

Infectious diseases

It has been studied in AIDS-related

Kaposi's sarcoma Kaposi's sarcoma (KS) is a type of cancer that can form masses in the skin, in lymph nodes, in the mouth, or in other organs. The skin lesions are usually painless, purple and may be flat or raised. Lesions can occur singly, multiply in a limit ...

West Nile virus West Nile virus (WNV) is a single-stranded RNA virus that causes West Nile fever. It is a member of the family '' Flaviviridae'', from the genus '' Flavivirus'', which also contains the Zika virus, dengue virus, and yellow fever virus. The v ...

, and to inactivate '' Staphylococcus aureus'', and HIV-1. Phenothiazine dyes and light have been known to have virucidal properties for over 70 years.

References

External links

* * {{DEFAULTSORT:Methylene Blue Antidotes Genetics techniques Histology Redox indicators Thiazine dyes Vital stains World Health Organization essential medicines Monoamine oxidase inhibitors Phenothiazines Chlorides Wikipedia medicine articles ready to translate Dimethylamino compounds