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Methylene blue



Methylene blue
IUPAC name 3,7-bis(Dimethylamino)-
phenazathionium chloride
Tetramethylthionine chloride
Identifiers
CAS number 61-73-4
SMILES CN(C)c3ccc2nc1ccc(N(C)
C)cc1[s+]c2c3.[Cl-]
Properties
Molecular formula C16H18N3ClS
Molar mass 319.85 g/mol
Melting point

100-110 °C (with decomposion)

Boiling point

Decomposes

Except where noted otherwise, data are given for
materials in their standard state
(at 25 °C, 100 kPa)

Infobox disclaimer and references

Methylene blue is a heterocyclic aromatic chemical compound with molecular formula: C16H18ClN3S. It has many uses in a range of different fields, such as biology or chemistry. At room temperature it appears as a solid, odorless, dark green powder, that yields a blue solution when dissolved in water. Methylene blue should not be confused with methyl blue, another histology stain, new methylene blue, nor with the methyl violets often used as pH indicators.

Additional recommended knowledge

Contents

Uses

Chemistry

Methylene blue is widely used as a redox indicator in analytical chemistry. 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 in general chemistry, the "blue bottle" experiment. Typically, a solution is made of dextrose, methylene blue, and sodium hydroxide. Upon shaking the bottle, oxygen 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 oxygen is entirely consumed, the solution will turn colorless. Methylene blue is also used to make the reaction between Fehling's solution and reducing sugars more visible.

Biology

In biology methylene blue is used as a dye for a number of different staining procedures, such as Gram's stain, 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.

It can also be used as an indicator to determine if a cell such as yeast is alive or not. The blue indicator turns colourless in the presence of active enzymes, thus indicating living cells. However if it stays blue it doesn't mean that the cell is dead - the enzymes could be inactive/denatured. It must be noted that methylene blue can inhibit the respiration of the yeast as it picks up hydrogen ions made during the process. The yeast cell cannot then use those ions to release energy.

In neuroscience, methylene blue can also serve as a non-selective inhibitor of NO synthase.

Medicine

Owing to its reducing agent properties, methylene blue is employed as a medication for the treatment of methemoglobinemia, which can arise from ingestion of certain pharmaceuticals or broad beans. Basically, methylene blue acts to reduce the heme group from methemoglobin to hemoglobin. Methylene blue also blocks accumulation of cyclic guanosine monophosphate (cGMP) by inhibiting the enzyme guanylate cyclase: this action results in reduced responsiveness of vessels to cGMP-dependent vasodilators like nitric oxide and carbon monoxide.

Methylene blue is used in endoscopic 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, or pre-cancerous lesions.

Methylene blue was used at the end of the century as a successful treatment for malaria. It disappeared as an anti-malarial during the wars in Asia, as U.S. soldiers disliked its two inevitable, fully reversible side effects: green urine and blue sclera. Interest in its use has recently been revived,[1] especially because it is very cheap. Several clinical trials are in progress, trying to find a suitable drug combination. Initial attempts to combine methylene blue with chloroquine were disappointing;[2] however, more recent attempts have appeared more promising.

In surgeries such as sentinel lymph node dissections, methylene blue can be used to visually trace the lymphatic drainage of pertinent tissues. Similarly, methylene blue is added to bone cement 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.

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 M. Brooks in San Francisco.[3] Methylene blue was also used at mid-century in the treatment of carbon monoxide poisoning.[3]

Methylene blue is probably a monoamine oxidase inhibitor, and if infused intravenously at doses exceeding 5 mg/kg, may precipitate serious serotonin toxicity, serotonin syndrome, if combined with any selective serotonin reuptake inhibitors (SSRIs) or other serotonin reuptake inhibitor (e.g., duloxetine, sibutramine, venlafaxine, clomipramine, imipramine).[4]

Another, less well-known use of methylene blue is its utility for treating ifosfamide neurotoxicity. Methylene blue was first reported for treatment and prophylaxis of ifosfamide neuropsychiatric toxicity in 1994. A toxic metabolite of ifosfamide, chloracetaldehyde (CAA), disrupts the mitochondrial respiratory chain, 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.[5] 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 at 50-60mg up to six doses a day have resulted in improvement of symptoms within 10 minutes to several days.[6] Alternatively, it has been suggested that intravenous methylene blue 50mg every six hours for prophylaxis during ifosfamide treatment in patients with history of ifosfamide neuropsychiatric toxicity.[7] Prophylactic administration of 50mg of methylene blue the day before initiation of ifosfamide, and 50mg three times daily during ifosfamide chemotherapy has been recommended to lower the occurrence of ifosfamide neurotoxicity.[8]

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, the parasitic protozoa Ichthyophthirius multifiliis.

Pranks

Methylene blue is highly stable in the human body, and if ingested, it resists the acidic environment of the stomach as well as the many hydrolytic enzymes present. It is not significantly metabolized by the liver, and is instead quickly filtered out by the kidneys. A common prank among chemists and biochemists of the early and middle 20th century was to add small amounts of methylene blue (generally a few drops of a stain solution sufficed) to coffee, cola, or another dark beverage.[citation needed] The stain's color was masked by the beverage, and its taste is fairly faint. Within a few hours, the methylene blue was removed by the prank victim's kidneys, which caused his or her urine to change color[9] The urine may become green if little methylene blue was added; larger amounts create a deep blue color. The prank is fairly harmless if small amounts of methylene blue are used.

An episode of M*A*S*H, "Sons and Bowlers", showed Major Winchester using a dose of methylene blue to take down a rival camp's bowling champion during a contest. The champ panics when his urine turns blue, and listens to Winchester's advice to refrain from all exercise – including bowling, which allows the 4077th to win.

Adverse Reactions

Cardiovascular Central Nervous System Dematologic Gastrointestinal Genitourinary Hematologic
•Hypertension
•Precordial pain
•Dizziness
•Mental confusion
•Headache
•Fever
•Staining of skin
•Injection site necrosis (SC)
•Fecal discoloration
•Nausea
•Vomiting
•Abdominal pain
•Discoloration of urine
•Bladder irritation
•Anemia
[10][11]

References

  1. ^ Schirmer H, Coulibaly B, Stich A, et al. (2003). "Methylene blue as an antimalarial agent—past and future". Redox Rep. 8: 272–76. doi:10.1179/135100003225002899.
  2. ^ Meissner PE, Mandi G, Coulibaly B, et al. (2006). "Methylene blue for malaria in Africa: results from a dose-finding study in combination with chloroquine". Malaria Journal 5: 84. doi:10.1186/1475-2875-5-84.
  3. ^ a b Matilda Moldenhauer Brooks (1936). "Methylene Blue as an Antidote for Cyanide and Carbon Monoxide Poisoning". The Scientific Monthly 43 (6): 585-586.
  4. ^ Gillman PK. (2006). "Methylene Blue implicated in potentially fatal serotonin toxicity". Anaesthesia 61: 1013-14. doi:10.1111/j.1365-2044.2006.04808.x.
  5. ^ Yesne AE. (2007). "Ifosfamide neuropsychiatric toxicity in patients with cancer". Psychooncology 9999.
  6. ^ Patel PN. (2006). "Methylene blue for management of ifosfamide induced encephalopathy". Ann Pharmacother 40: 266-303.
  7. ^ Dufour C. (2006). "Ifosfamide induced encephalopathy". Arch Pediatr 13: 140-145.
  8. ^ Aeschlimann T. (1996). "nhibition of (mono)amine oxidase activity and prevention of ifosfamide encephalopathy by methylene blue". Drug Metab Dispos 24: 1336-1339.
  9. ^ Medical use with side effects indicating blue urine. Medicinenet.com.
  10. ^ Mokhlesi B. (2003). "Adult Toxicology in Critical Care: Part II: Specific Poisonings". Chest 123: 897.
  11. ^ Harvey JW. (1983). "Studies of the Efficacy and Potential Hazards of Methylene Blue Therapy in Aniline-Induced Methaemoglobinaemia". Br J Haemotol 54: 29.

See also

 
This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Methylene_blue". A list of authors is available in Wikipedia.
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