Wikipedia:WikiProject Chemicals/Chembox validation/VerifiedDataSandbox and Methylene blue: Difference between pages

{{Short description|Blue dye also used as a medication}}

{{Distinguish|methyl blue|new methylene blue|methyl violet}}

| verifiedrevid = 464380613

| caption = Molecular structure

| image2 = Reflections in a flask of Methylene Blue.jpg

| caption2 = A volumetric flask of a methylene blue solution

| tradename = Urelene blue, Provayblue, Proveblue, others<ref name=Ric2015>{{cite book| vauthors = Hamilton R |title=Tarascon Pocket Pharmacopoeia 2015 Deluxe Lab-Coat Edition|date=2015|publisher=Jones & Bartlett Learning|isbn=9781284057560|page=471}}</ref><ref name=BNF69/>

| Drugs.com = {{drugs.com|monograph|methylene-blue}}

| DailyMedID = Provayblue

| pregnancy_AU = D

| pregnancy_category =

| routes_of_administration = [[By mouth]], [[Intravenous therapy|intravenous]]

| ATC_prefix = V03

| ATC_suffix = AB17

| ATC_supplemental = {{ATC|V04|CG05}}

| legal_US = Rx-only

| legal_US_comment = <ref name="Provayblue FDA label">{{cite web | title=Provayblue- methylene blue injection | website=DailyMed | date=29 June 2022 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=4f6848e5-35ed-4046-b13c-3032b5ba3232 | access-date=4 March 2023}}</ref><ref name=AHFS2017/>

| legal_EU = Rx-only

| legal_EU_comment = <ref name="Lumeblue EPAR">{{cite web | title=Lumeblue EPAR | website=European Medicines Agency | date=19 June 2020 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/lumeblue | access-date=4 March 2023}}</ref><ref>{{cite web | title=Lumeblue Product information | website=Union Register of medicinal products | url=https://ec.europa.eu/health/documents/community-register/html/h1470.htm | access-date=3 March 2023}}</ref>

| bioavailability =

| protein_bound =

| metabolism =

| elimination_half-life = 5 to 24 hours<ref name=AHFS2017/>

| excretion =

| DrugBank = DB09241

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = 8NAP7826UB

| KEGG = D10537

| KEGG2 = C00220

| synonyms = [[Colour Index International|CI]] 52015, basic blue 9<ref name="Lillie, 1977">{{cite book | vauthors = Lillie RD |title=H. J. Conn's Biological stains |date=1977 |publisher=Williams & Wilkins |location=Baltimore |pages=692p |edition=9th}}</ref>

| IUPAC_name = 3,7-bis(Dimethylamino)-phenothiazin-5-ium chloride| chemical_formula =

| C=16 | H=18 | Cl=1 | N=3 | S=1

| SMILES = CN(C)c1ccc2c(c1)sc-3cc(=[N+](C)C)ccc3n2.[Cl-]

<!-- Definition and uses -->

'''Methylthioninium chloride''', commonly called '''methylene blue''', is a salt used as a [[dye]] and as a medication. As a medication, it is mainly used to treat [[methemoglobinemia]] by [[redox|chemically reducing]] the [[ferric iron]] in [[hemoglobin]] to [[ferrous iron]].<ref name=AHFS2017/><ref name="BNF69">{{cite book |title=British national formulary : BNF 69 |date=2015 |publisher=British Medical Association |isbn=9780857111562 |edition=69 |page=34}}</ref> Specifically, it is used to treat methemoglobin levels that are greater than 30% or in which there are symptoms despite [[oxygen therapy]].<ref name=BNF69/> It has previously been used for treating [[cyanide poisoning]] and [[urinary tract infections]], but this use is no longer recommended.<ref name=AHFS2017/>

<!-- Side effects and mechanism -->

Methylene blue is typically given by [[intravenous|injection into a vein]].<ref name=AHFS2017>{{cite web|title=Methylene Blue|url=https://www.drugs.com/monograph/methylene-blue.html|publisher=The American Society of Health-System Pharmacists|access-date=8 January 2017|url-status=live|archive-url=https://web.archive.org/web/20170510111253/https://www.drugs.com/monograph/methylene-blue.html|archive-date=10 May 2017}}</ref> Common side effects include headache and vomiting. While use during [[pregnancy]] may harm the fetus, not using it in methemoglobinemia is likely more dangerous.<ref name=AHFS2017/><ref name=BNF69/>

<!-- History and culture -->

Methylene blue was first prepared in 1876, by [[Heinrich Caro]].<ref name=Ah2008>{{cite book| vauthors = Ahmad I, Aqil F |title=New Strategies Combating Bacterial Infection |date=2008 |publisher=John Wiley & Sons |isbn=9783527622948 |page=91 |url=https://books.google.com/books?id=Hrdzorisyp8C&pg=PA91 |language=en |url-status=live |archive-url=https://web.archive.org/web/20170918205927/https://books.google.com/books?id=Hrdzorisyp8C&pg=PA91|archive-date=2017-09-18}}</ref> It is on the [[WHO Model List of Essential Medicines|World Health Organization's List of Essential Medicines]].<ref name="WHO21st">{{cite book | vauthors = ((World Health Organization)) | title = World Health Organization model list of essential medicines: 21st list 2019 | year = 2019 | hdl = 10665/325771 | author-link = World Health Organization | publisher = World Health Organization | location = Geneva | id = WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO }}</ref>

==Uses==

===Methemoglobinemia===

Methylene blue is employed as a medication for the treatment of [[methemoglobinemia]], which can arise from ingestion of certain pharmaceuticals, toxins, or [[Vicia faba|broad beans]] in those susceptible.<ref>{{cite book | vauthors = Thomé SD, Petz LD | chapter = Hemolytic Anemia: Hereditary and Acquired | veditors = Mazza J |title=Manual of Clinical Hematology |date=2002 |publisher=Lippincott Williams & Wilkins |location=Philadelphia |isbn=978-0-7817-2980-2 |page=102 |edition=3rd | chapter-url = https://books.google.com/books?id=NzMKMPzbxZwC&pg=PA102 }}</ref> Normally, through the [[NADH]]- 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]] group from [[methemoglobin]] to [[hemoglobin]]. Methylene blue can reduce the half life of methemoglobin from hours to minutes.<ref name="brent">

{{Cite book| author =Brent J.| title =Critical care toxicology: diagnosis and management of the critically poisoned patient.| publisher = [[Elsevier Health Sciences]]| year =2005 }}</ref> At high doses, however, methylene blue actually induces methemoglobinemia, reversing this pathway.<ref name="brent"/>

===Methylphen===

{{excerpt|Hyoscyamine/hexamethylenetetramine/phenyl salicylate/methylene blue/benzoic acid|paragraphs=1}}

===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,<ref name = "brooks" /> although first demonstrated by Bo Sahlin of [[Lund University]], in 1926.<ref name = "brooks">{{Cite journal | title = Methylene blue as an antidote for cyanide and carbon monoxide poisoning | vauthors = Brooks MM | journal = The Scientific Monthly | volume = 43 | issue = 6 | year = 1936 | pages = 585–586| jstor =16280| bibcode = 1936SciMo..43..585M }}</ref><ref>{{cite journal | doi = 10.1001/jama.1933.02740050053028| title = Methylene Blue As Antidote for Cyanide Poisoning| journal = JAMA| volume = 100| issue = 5| pages = 357| date = 4 February 1933| vauthors = Hanzlik PJ }}</ref>

===Dye or stain===

[[File:Human Cheek Cells.jpg|thumb|280x280px|Human cheek cells stained with methylene blue]]

[[File:Methylene blue Crystals.jpg|thumb|Methylene blue crystals]]

Methylene blue is used in [[colonoscopy|endoscopic]] [[polyp (medicine)|polypectomy]] as an adjunct to [[Saline (medicine)|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 [[endoscopy|chromoendoscopy]], and is sprayed onto the mucosa of the [[gastrointestinal tract]] in order to identify [[dysplasia]], or pre-cancerous lesions. Intravenously injected methylene blue is readily released into the urine and thus can be used to test the [[urinary tract]] for leaks or [[fistula]]s.{{Citation needed|date=January 2021}}

In surgeries such as [[sentinel lymph node]] dissections, methylene blue can be used to visually trace the lymphatic drainage of tested 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. Methylene blue is used as an aid to visualisation/orientation in a number of medical devices, including a [[Surgical sealant film]], TissuePatch. In [[fistula]]s and [[pilonidal sinus]]es it is used to identify the tract for complete excision.{{citation needed|date=April 2018}} It can also be used during gastrointestinal surgeries (such as [[bowel resection]] or [[gastric bypass surgery|gastric bypass]]) to test for leaks.{{Citation needed|date=January 2021}}

It is sometimes used in [[cytopathology]], in mixtures including [[Wright-Giemsa]] and [[Diff-Quik]]. It confers a blue color to both nuclei and cytoplasm, and makes the nuclei more visible.<ref name="pmid26664363">{{cite journal | vauthors = Hu X, Laguerre V, Packert D, Nakasone A, Moscinski L | title = A Simple and Efficient Method for Preparing Cell Slides and Staining without Using Cytocentrifuge and Cytoclips | journal = International Journal of Cell Biology | volume = 2015 | issue = | pages = 813216 | year = 2015 | pmid = 26664363 | pmc = 4664808 | doi = 10.1155/2015/813216 | doi-access = free }}</ref> When methylene blue is "polychromed" (oxidized in solution or "ripened" by fungal metabolism,<ref>{{Cite book | vauthors = Kiernan JA | chapter = Chapter 19: On Chemical Reactions and Staining Mechanisms | series = Education Guide | veditors = Kumar GL, Kiernan JA | title = Special Stains and H & E | date = 2010 | edition = Second | location = Carpinteria, California | publisher = Dako North America, Inc. |chapter-url= http://www.dako.com/08066_12may10_webchapter19.pdf |archive-url= https://web.archive.org/web/20120513002342/http://www.dako.com/08066_12may10_webchapter19.pdf |url-status=dead | quote = What is Giemsa's stain and how does it color blood cells, bacteria and chromosomes? | page = 172 |archive-date=May 13, 2012}}</ref> as originally noted in the thesis of [[Romanowsky stain|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 A]], [[Azure C]], and [[thionine]], respectively.<ref>{{cite journal | vauthors = Wilson TM | title = On the Chemistry and Staining Properties of Certain Derivatives of the Methylene Blue Group When Combined With Eosin | journal = The Journal of Experimental Medicine | volume = 9 | issue = 6 | pages = 645–670 | date = November 1907 | pmid = 19867116 | pmc = 2124692 | doi = 10.1084/jem.9.6.645 }}</ref> This is the basis of the basophilic part of the spectrum of [[Romanowsky stain|Romanowski-Giemsa]] effect. If only synthetic Azure B and [[Eosin Y]] is used, it may serve as a standardized [[Giemsa stain]]; 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).<ref>{{cite book | vauthors = Lewis SM, Bain BK, Bates I, Dacie JV |title=Dacie and Lewis practical haematology |date=2006 |publisher=Churchill Livingstone/Elsevier |location=Philadelphia, PA |isbn=978-0-443-06660-3 |edition=10th | page = 61 }}</ref>

A traditional application of methylene blue is the intravital or supravital staining of nerve fibers, an effect first described by [[Paul Ehrlich]] in 1887.<ref>{{cite journal | vauthors = Ehrlich P | date = 1887 | title = Ueber die Methylenblau Reaktion der lebenden Nerven Substanz. | trans-title = About the methylene blue reaction of the living nerve substance. | language = German | journal =Biologisches Zentralblatt | trans-journal = Biological Central Journal | volume = 6 | pages = 214–224 | url = https://www.pei.de/SharedDocs/Downloads/DE/institut/veroeffentlichungen-von-paul-ehrlich/1886-1896/1887-ueber-methylenblaureaktion-lebender-nervensubstanz.pdf?__blob=publicationFile&v=2 }} cited by {{cite book | vauthors = Baker JR | title = Principles of biological microtechnique. A study of fixation and dyeing. | date = 1958 | location = London | publisher = Methuen }}</ref> 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.<ref>{{cite journal | vauthors = Wilson JG | title = Intra vitam staining with methylene blue. | journal = The Anatomical Record | date = July 1910 | volume = 4 | issue = 7 | pages = 267–277 | doi = 10.1002/ar.1090040705 | s2cid = 86242668 | url = https://zenodo.org/record/2478243 }}</ref><ref>{{cite journal | vauthors = Schabadasch A | title = Untersuchungen zur Methodik der Methylenblaufärbung des vegetativen Nervensystems. | trans-title = Investigations on the methodology of methylene blue staining of the autonomic nervous system. | language = German | journal = Zeitschrift für Zellforschung und Mikroskopische Anatomie | trans-journal = Journal of Cell Research and Microscopic Anatomy | date = January 1930 | volume = 10 | issue = 2 | pages = 221–243 | doi = 10.1007/BF02450696 | s2cid = 36940327 }}</ref><ref>{{cite book | vauthors = Zacks SI | date = 1973 | title = The Motor Endplate | edition = 2nd | location = Huntington, NY | publisher = Krieger }}</ref> 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.<ref name="Kiernan_1974">{{cite journal | vauthors = Kiernan JA | title = Effects of metabolic inhibitors on vital staining with methylene blue | journal = Histochemistry | volume = 40 | issue = 1 | pages = 51–7 | date = June 1974 | pmid = 4136702 | doi = 10.1007/BF00490273 | s2cid = 23158612 }}</ref>

===Placebo===

Methylene blue has been used as a [[placebo]]; physicians would tell their patients to expect their urine to change color and view this as a sign that their condition had improved.<ref>{{Cite web| url =http://www.sciencebasedmedicine.org/?p=29| title =The ethics of deception in medicine| access-date =2008-01-24| vauthors = Novella S | work =Science Based Medicine| date =23 January 2008| url-status =live| archive-url =https://web.archive.org/web/20080129230034/http://www.sciencebasedmedicine.org/?p=29| archive-date =2008-01-29}}</ref> This same side effect makes methylene blue difficult to use in traditional placebo-controlled [[clinical studies]], including those testing for its efficacy as a treatment.<ref>{{ClinicalTrialsGov|NCT00214877|Methylene blue for cognitive dysfunction in bipolar disorder}}</ref>

===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]].<ref>{{cite journal | vauthors = Taylor GM, Avera RS, Strachan CC, Briggs CM, Medler JP, Pafford CM, Gant TB | title = Severe methemoglobinemia secondary to isobutyl nitrite toxicity: the case of the 'Gold Rush' | journal = Oxford Medical Case Reports | volume = 2021 | issue = 2 | pages = omaa136 | date = February 2021 | pmid = 33614047 | pmc = 7885148 | doi = 10.1093/omcr/omaa136 }}</ref> Severe methemoglobinemia may be treated with methylene blue.<ref>{{cite journal | vauthors = Modarai B, Kapadia YK, Kerins M, Terris J | title = Methylene blue: a treatment for severe methaemoglobinaemia secondary to misuse of amyl nitrite | journal = Emergency Medicine Journal | volume = 19 | issue = 3 | pages = 270–271 | date = May 2002 | pmid = 11971852 | pmc = 1725875 | doi = 10.1136/emj.19.3.270 }}</ref>

[[File:Gross pathology of normal brain and brain of patient treated with methylene blue before death.jpg|thumb|Gross pathology of a normal brain and a brain of a patient treated with methylene blue before death.]]

===Ifosfamide toxicity===

Another use of methylene blue is to treat [[ifosfamide]] [[neurotoxicity]]. Methylene blue was first reported for treatment and [[prophylaxis]] of ifosfamide neuropsychiatric toxicity in 1994. A toxic metabolite of ifosfamide, [[chloroacetaldehyde]] (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.<ref>

{{cite journal | vauthors = Alici-Evcimen Y, Breitbart WS | title = Ifosfamide neuropsychiatric toxicity in patients with cancer | journal = Psycho-Oncology | volume = 16 | issue = 10 | pages = 956–960 | date = October 2007 | pmid = 17278152 | doi = 10.1002/pon.1161 | s2cid = 27433170 | doi-access = free }}</ref> 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.<ref>

{{cite journal | vauthors = Patel PN | title = Methylene blue for management of Ifosfamide-induced encephalopathy | journal = The Annals of Pharmacotherapy | volume = 40 | issue = 2 | pages = 299–303 | date = February 2006 | pmid = 16391008 | doi = 10.1345/aph.1G114 | s2cid = 21124635 }}</ref> 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.<ref>

{{cite journal | vauthors = Dufour C, Grill J, Sabouraud P, Behar C, Munzer M, Motte J, Oberlin O, Paci A, Hartmann O | display-authors = 6 | title = [Ifosfamide induced encephalopathy: 15 observations] | language = fr | journal = Archives de Pédiatrie | volume = 13 | issue = 2 | pages = 140–145 | date = February 2006 | pmid = 16364615 | doi = 10.1016/j.arcped.2005.10.021 | name-list-style = vanc }}</ref> 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.<ref>

{{cite journal | vauthors = Aeschlimann C, Cerny T, Küpfer A | title = Inhibition of (mono)amine oxidase activity and prevention of ifosfamide encephalopathy by methylene blue | journal = Drug Metabolism and Disposition | volume = 24 | issue = 12 | pages = 1336–1339 | date = December 1996 | pmid = 8971139 }}</ref>

===Shock===

It has also been used in [[septic shock]] and [[anaphylaxis]].<ref name=Jang2013>{{cite journal | vauthors = Jang DH, Nelson LS, Hoffman RS | title = Methylene blue for distributive shock: a potential new use of an old antidote | journal = Journal of Medical Toxicology | volume = 9 | issue = 3 | pages = 242–249 | date = September 2013 | pmid = 23580172 | pmc = 3770994 | doi = 10.1007/s13181-013-0298-7 }}</ref><ref name=Paciullo2010>{{cite journal | vauthors = Paciullo CA, McMahon Horner D, Hatton KW, Flynn JD | title = Methylene blue for the treatment of septic shock | journal = Pharmacotherapy | volume = 30 | issue = 7 | pages = 702–715 | date = July 2010 | pmid = 20575634 | doi = 10.1592/phco.30.7.702 | s2cid = 759538 }}</ref>

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.<ref>{{cite journal | vauthors = Hosseinian L, Weiner M, Levin MA, Fischer GW | title = Methylene Blue: Magic Bullet for Vasoplegia? | journal = Anesthesia and Analgesia | volume = 122 | issue = 1 | pages = 194–201 | date = January 2016 | pmid = 26678471 | doi = 10.1213/ANE.0000000000001045 | s2cid = 26114442 }}</ref><ref>{{cite journal | vauthors = Levin RL, Degrange MA, Bruno GF, Del Mazo CD, Taborda DJ, Griotti JJ, Boullon FJ | title = Methylene blue reduces mortality and morbidity in vasoplegic patients after cardiac surgery | journal = The Annals of Thoracic Surgery | volume = 77 | issue = 2 | pages = 496–499 | date = February 2004 | pmid = 14759425 | doi = 10.1016/S0003-4975(03)01510-8 }}</ref><ref name="Leite_2006">{{cite journal | vauthors = Leite EG, Ronald A, Rodrigues AJ, Evora PR | title = Is methylene blue of benefit in treating adult patients who develop catecholamine-resistant vasoplegic syndrome during cardiac surgery? | journal = Interactive Cardiovascular and Thoracic Surgery | volume = 5 | issue = 6 | pages = 774–8 | date = December 2006 | pmid = 17670710 | doi = 10.1510/icvts.2006.134726 | s2cid = 30259038 | url = http://www.bestbets.org/bets/bet.php?id=911 }}</ref><ref>{{cite journal | vauthors = Stawicki SP, Sims C, Sarani B, Grossman MD, Gracias VH | title = Methylene blue and vasoplegia: who, when, and how? | journal = Mini Reviews in Medicinal Chemistry | volume = 8 | issue = 5 | pages = 472–490 | date = May 2008 | pmid = 18473936 | doi = 10.2174/138955708784223477 | url = http://www.bentham-direct.org/pages/content.php?MRMC/2008/00000008/00000005/0006N.SGM | access-date = 2020-04-01 | url-status = usurped | archive-url = https://web.archive.org/web/20170918205928/http://www.bentham-direct.org/pages/content.php?MRMC%2F2008%2F00000008%2F00000005%2F0006N.SGM | archive-date = 2017-09-18 }}</ref>

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.<ref>{{cite journal | vauthors = Fadhlillah F, Patil S | title = Pharmacological and mechanical management of calcium channel blocker toxicity | journal = BMJ Case Reports | volume = 2018 | pages = bcr2018225324 | date = August 2018 | pmid = 30150339 | pmc = 6119390 | doi = 10.1136/bcr-2018-225324 }}</ref><ref>{{cite journal | vauthors = Saha BK, Bonnier A, Chong W | title = Rapid reversal of vasoplegia with methylene blue in calcium channel blocker poisoning | journal = African Journal of Emergency Medicine | volume = 10 | issue = 4 | pages = 284–287 | date = December 2020 | pmid = 33299766 | pmc = 7700985 | doi = 10.1016/j.afjem.2020.06.014 }}</ref><ref>{{cite journal | vauthors = Aggarwal N, Kupfer Y, Seneviratne C, Tessler S | title = Methylene blue reverses recalcitrant shock in β-blocker and calcium channel blocker overdose | journal = BMJ Case Reports | volume = 2013 | pages = bcr2012007402 | date = January 2013 | pmid = 23334490 | pmc = 3604019 | doi = 10.1136/bcr-2012-007402 }}</ref><ref>{{cite journal | vauthors = Pellegrini JR, Munshi R, Tiwana MS, Abraham T, Tahir H, Sayedy N, Iqbal J | title = "Feeling the Blues": A Case of Calcium Channel Blocker Overdose Managed With Methylene Blue | journal = Cureus | volume = 13 | issue = 10 | pages = e19114 | date = October 2021 | pmid = 34868762 | pmc = 8627593 | doi = 10.7759/cureus.19114 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Ahmed S, Barnes S | title = Hemodynamic improvement using methylene blue after calcium channel blocker overdose | journal = World Journal of Emergency Medicine | volume = 10 | issue = 1 | pages = 55–58 | date = 2019 | pmid = 30598720 | pmc = 6264975 | doi = 10.5847/wjem.j.1920-8642.2019.01.009 }}</ref><ref>{{cite journal | vauthors = Burkes R, Wendorf G | title = A multifaceted approach to calcium channel blocker overdose: a case report and literature review | journal = Clinical Case Reports | volume = 3 | issue = 7 | pages = 566–569 | date = July 2015 | pmid = 26273444 | pmc = 4527798 | doi = 10.1002/ccr3.300 }}</ref><ref>{{cite journal | vauthors = Chudow M, Ferguson K | title = A Case of Severe, Refractory Hypotension After Amlodipine Overdose | journal = Cardiovascular Toxicology | volume = 18 | issue = 2 | pages = 192–197 | date = April 2018 | pmid = 28688059 | doi = 10.1007/s12012-017-9419-x | s2cid = 3713149 }}</ref><ref>{{cite journal | vauthors = Jang DH, Nelson LS, Hoffman RS | title = Methylene blue in the treatment of refractory shock from an amlodipine overdose | journal = Annals of Emergency Medicine | volume = 58 | issue = 6 | pages = 565–567 | date = December 2011 | pmid = 21546119 | doi = 10.1016/j.annemergmed.2011.02.025 }}</ref><ref>{{cite journal | vauthors = Laes JR, Williams DM, Cole JB | title = Improvement in Hemodynamics After Methylene Blue Administration in Drug-Induced Vasodilatory Shock: A Case Report | journal = Journal of Medical Toxicology | volume = 11 | issue = 4 | pages = 460–463 | date = December 2015 | pmid = 26310944 | pmc = 4675606 | doi = 10.1007/s13181-015-0500-1 }}</ref>{{citation overkill|date=July 2022}}

==Side effects==

{| class="wikitable"

|-

! Cardiovascular<ref name="Mokhlesi2003">{{cite journal | vauthors = Mokhlesi B, Leikin JB, Murray P, Corbridge TC | title = Adult toxicology in critical care: Part II: specific poisonings | url = https://journal.chestnet.org/article/S0012-3692(16)34761-4/fulltext | journal = Chest | volume = 123 | issue = 3 | pages = 897–922 | date = March 2003 | pmid = 12628894 | doi = 10.1378/chest.123.3.897 | s2cid = 9962335 }}</ref><ref name="Harvey1983">{{cite journal | vauthors = Harvey JW, Keitt AS | title = Studies of the efficacy and potential hazards of methylene blue therapy in aniline-induced methaemoglobinaemia | url = https://onlinelibrary.wiley.com/doi/10.1111/j.1365-2141.1983.tb02064.x | journal = British Journal of Haematology | volume = 54 | issue = 1 | pages = 29–41 | date = May 1983 | pmid = 6849836 | doi = 10.1111/j.1365-2141.1983.tb02064.x | s2cid = 19304915 }}</ref>

! Central Nervous System<ref name="Mokhlesi2003" /><ref name="Harvey1983" />

! Dermatologic<ref name="Mokhlesi2003" /><ref name="Harvey1983" />

! Gastrointestinal<ref name="Mokhlesi2003" /><ref name="Harvey1983" />

! Genito-urinary<ref name="Mokhlesi2003" /><ref name="Harvey1983" />

! Hematologic<ref name="Mokhlesi2003" /><ref name="Harvey1983" />

|-

| • [[Hypertension]]<br />• [[Precordial]] [[pain]]

| • [[Dizziness]]<br />• Mental confusion<br />• [[Headache]]<br />• [[Fever]]

| • Staining of skin<br />• Injection site [[necrosis]] (SC)

| • Fecal discoloration<br />• [[Nausea]]<br />• [[Vomiting]]<br />• [[Abdominal]] [[pain]]

| • Discoloration of [[urine]] (doses over 80&nbsp;μg)<br />• [[Bladder]] irritation

| • [[Anemia]]

|}

Methylene blue is a [[monoamine oxidase inhibitor]] (MAOI),<ref>

{{cite journal | vauthors = Ramsay RR, Dunford C, Gillman PK | title = Methylene blue and serotonin toxicity: inhibition of monoamine oxidase A (MAO A) confirms a theoretical prediction | journal = British Journal of Pharmacology | volume = 152 | issue = 6 | pages = 946–951 | date = November 2007 | pmid = 17721552 | pmc = 2078225 | doi = 10.1038/sj.bjp.0707430 }}</ref> and if infused intravenously at doses exceeding 5&nbsp;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]]).<ref name="pmid16978328">{{cite journal | vauthors = Gillman PK | title = Methylene blue implicated in potentially fatal serotonin toxicity | journal = Anaesthesia | volume = 61 | issue = 10 | pages = 1013–1014 | date = October 2006 | pmid = 16978328 | doi = 10.1111/j.1365-2044.2006.04808.x | s2cid = 45063314 | doi-access = }}</ref>

It causes [[hemolytic anemia]] in carriers of the [[G6PD]] ([[favism]]) enzymatic deficiency.<ref>{{cite journal | vauthors = Rosen PJ, Johnson C, McGehee WG, Beutler E | title = Failure of methylene blue treatment in toxic methemoglobinemia. Association with glucose-6-phosphate dehydrogenase deficiency | journal = Annals of Internal Medicine | volume = 75 | issue = 1 | pages = 83–86 | date = July 1971 | pmid = 5091568 | doi = 10.7326/0003-4819-75-1-83 }}</ref>

==Chemistry==

Methylene blue is a formal derivative of [[phenothiazine]]. It is a dark green powder that yields a blue solution in [[water (molecule)|water]]. The hydrated form has 3 molecules of water per unit of methylene blue.

===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:<ref name=ull>{{cite encyclopedia| vauthors = Berneth H |chapter=Azine Dyes |encyclopedia= Ullmann's Encyclopedia of Industrial Chemistry |year=2012 |publisher=Wiley-VCH |place=Weinheim |doi=10.1002/14356007.a03_213.pub3|isbn=978-3527306732}}</ref>

:[[File:Synthesis of methylene blue.png|600px]]

A green electrochemical procedure, using only [[dimethyl-4-phenylenediamine]] and sulfide ions has been proposed.<ref>{{Cite journal | vauthors = Maleki A, Nematollahi D |date=December 2009 |title=An efficient electrochemical method for the synthesis of methylene blue |url=https://linkinghub.elsevier.com/retrieve/pii/S1388248109004846 |journal=Electrochemistry Communications |language=en |volume=11 |issue=12 |pages=2261–2264 |doi=10.1016/j.elecom.2009.09.040}}</ref>

===Light absorption properties===

[[File:Methylene blue absorption spectrum.png|thumb|Absorption spectrum of methylene blue, in terms of the [[molar extinction coefficient]] (base 10 logarithm). In this dataset a peak [[absorbance]] of 1.7 (i.e. 98% of transmitted light absorbed) was observed with 665 nm light passing through 1 cm of 10 micromolar methylene blue solution.]]

The maximum absorption of light is near 670&nbsp;nm. The specifics of absorption depend on a number of factors, including [[protonation]], [[adsorption]] to other materials, and [[metachromasy]] - the formation of [[Dimer (chemistry)|dimers]] and higher-order aggregates depending on concentration and other interactions:<ref>{{cite journal|title=Visible spectroscopy of methylene blue on hectorite, laponite B, and barasym in aqueous suspension| vauthors = Cenens J, Schoonheydt RA |journal=Clays and Clay Minerals |volume=36 |number=3 |pages=214–224 |year=1988 |doi=10.1346/ccmn.1988.0360302 |bibcode=1988CCM....36..214C | s2cid = 3851037 |doi-access=}}</ref>

{| class="wikitable"

!Species

!Absorption peak

!Extinction coefficient (dm³/mol·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 [[redox indicator]] in [[analytical chemistry]].<ref name="Cook1994">{{cite journal | vauthors = Cook AG, Tolliver RM, Williams JE |title=The Blue Bottle experiment revisited: How Blue? How Sweet? |journal=Journal of Chemical Education |date=February 1994 |volume=71 |issue=2 |pages=160 |doi=10.1021/ed071p160|bibcode=1994JChEd..71..160C }}</ref><ref name="Anderson2012">{{cite journal | vauthors = Anderson L, Wittkopp SM, Painter CJ, Liegel JJ, Schreiner R, Bell JA, Shakhashiri BZ |title=What is happening when the Blue Bottle bleaches: An Investigation of the methylene blue-catalyzed air oxidation of glucose |journal=Journal of Chemical Education |date=9 October 2012 |volume=89 |issue=11 |pages=1425–1431 |doi=10.1021/ed200511d|bibcode=2012JChEd..89.1425A }}</ref><ref name="Rajchakit2016">{{cite journal | vauthors = Rajchakit U, Limpanuparb T |title=Rapid Blue Bottle experiment: Autoxidation of benzoin catalyzed by redox indicators |journal=Journal of Chemical Education |date=9 August 2016 |volume=93 |issue=8 |pages=1490–1494 |doi=10.1021/acs.jchemed.6b00018|bibcode=2016JChEd..93.1490R }}</ref> Solutions of this substance are blue when in an oxidizing environment, but will turn colorless if exposed to a reducing agent.<ref name="Harvey1919">{{cite journal | vauthors = Harvey EN | title = The relation between the oxygen concentration and rate of reduction of methylene blue by milk | journal = The Journal of General Physiology | volume = 1 | issue = 4 | pages = 415–419 | date = March 1919 | pmid = 19871757 | pmc = 2140316 | doi = 10.1085/jgp.1.4.415 }}</ref><ref name="Anderson2012" /> The redox properties can be seen in a classical demonstration of [[chemical kinetics]] in general chemistry, the "[[Blue bottle (chemical reaction)|blue bottle]]" experiment. Typically, a solution is made of [[glucose]] (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 dextrose is entirely consumed, the solution will turn blue again. The redox midpoint potential E{{sub|0}}' is +0.01 V.<ref>{{cite book | vauthors = Jakubowski H | date = 2016 | chapter = Chapter 8: Oxidation/Phosphorylation B: Oxidative Enzymes | title = Biochemistry Online | chapter-url = https://employees.csbsju.edu/hjakubowski/classes/ch331/oxphos/oloxidativeenzymes.html }}</ref>

===Peroxide generator===

Methylene blue is also a [[photosensitizer]] used to create [[singlet oxygen]] when exposed to both oxygen and light. It is used in this regard to make organic [[peroxides]] by a [[Diels-Alder]] reaction which is [[selection rule#Electronic spectra|spin forbidden]] with normal atmospheric [[triplet oxygen]].{{Citation needed|date=January 2021}}

===Sulfide analysis===

The formation of methylene blue after the reaction of [[hydrogen sulfide]] with [[dimethyl-p-phenylenediamine]] and [[Ferric|iron(III)]] at pH&nbsp;0.4&nbsp;–&nbsp;0.7 is used to determine by [[Ultraviolet-visible spectroscopy|photometric measurements]] [[sulfide]] concentration in the range 0.020 to 1.50&nbsp;mg/L (20&nbsp;ppb to 1.5&nbsp;ppm).<ref name="Siegel1965">{{Cite journal |vauthors=Siegel Lewis M |date=1965-04-01 |title=A direct microdetermination for sulfide |url=https://dx.doi.org/10.1016/0003-2697%2865%2990051-5 |journal=Analytical Biochemistry |language=en |volume=11 |issue=1 |pages=126–132 |doi=10.1016/0003-2697(65)90051-5 |pmid=14328633 |issn=0003-2697}}</ref> The test is very sensitive and the blue coloration developing upon contact of the reagents with dissolved H₂S is stable for 60&nbsp;min. Ready-to-use kits such as the ''Spectroquant'' [[sulfide]] test<ref>{{cite web|url=http://photometry.merck.de/|title=Analytik und Probenvorbereitung|url-status=dead|archive-url=https://web.archive.org/web/20070315204844/http://photometry.merck.de/|archive-date=2007-03-15 | publisher = Merck KGaA | location = Darmstadt, Germany }}</ref> 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]] (SRB). In this colorimetric test, methylene blue is a product formed by the reaction and not a reagent added to the system.<ref name="Siegel1965" />

The addition of a strong [[reducing agent]], 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]], 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.<ref name="Anderson2012" />

===Test for milk freshness===

Methylene blue is a dye behaving as a [[redox indicator]] that is commonly used in the [[food industry]] to test the freshness of [[milk]] and [[dairy]] products.<ref name=AHFS2017/><ref name = "Thornton_1930">{{cite journal | vauthors = Thornton H |title=Studies on Oxidation-Reduction in Milk: The Methylene Blue Reduction Test |journal=Journal of Dairy Science |date=May 1930 |volume=13 |issue=3 |pages=221–245 |publisher=Elsevier Inc. |doi=10.3168/jds.S0022-0302(30)93520-5 |doi-access=free }}</ref> A few drops of methylene blue solution added to a sample of milk should remain blue (oxidized form in the presence of enough dissolved {{O2}}), otherwise (discoloration caused by the reduction of methylene blue into its colorless reduced form) the dissolved {{O2}} concentration in the milk sample is low indicating that the milk is not fresh (already abiotically oxidized by {{O2}} whose concentration in solution decreases) or could be contaminated by [[bacteria]] also consuming the atmospheric {{O2}} dissolved in the milk.<ref name = "Thornton_1930" /> In other words, [[Oxygenation (environmental)|aerobic]] conditions should prevail in fresh milk and methylene blue is simply used as an indicator of the dissolved oxygen remaining in the milk.<ref name="Harvey1919" />

===Water testing===

{{Further|MBAS assay}}

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 an acidified, aqueous methylene blue solution containing [[chloroform]] can detect [[anionic surfactant]]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]]s, [[phosphate]]s, [[sulfate]]s, and [[sulfonate]]s.{{citation needed|date=July 2022}}

===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&nbsp;g of [[activated carbon]] (dry basis).<ref>{{cite web | title = Test Methods for Activated Carbon | url = https://activatedcarbon.org/images/Test_method_for_Activated_Carbon_86.pdf | work = European Council of Chemical Manufacturers' Federations | date = April 1986 }}</ref>

Methylene blue value reflects the amount of clay minerals in [[construction aggregate|aggregate]] samples.<ref>{{cite report |url=http://www.astm.org/Standards/C1777.htm| id = ASTM C1777 | title = Standard Test Method for Rapid Determination of the Methylene Blue Value for Fine Aggregate or Mineral Filler Using a Colorimeter | date = 7 July 2020 | location = West Conshohocken, PA | publisher = ASTM (American Society for Testing and Material) International |url-status=live |archive-url= https://web.archive.org/web/20140228153812/http://www.astm.org/Standards/C1777.htm |archive-date=2014-02-28 | doi = 10.1520/C1777-20 }}</ref> 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.<ref>{{Cite web | author = Standing Committee on Concrete Technology (SCCT) |url= https://www.cedd.gov.hk/filemanager/eng/content_78/cs3_2013_original.pdf |title=Construction Standard CS3:2013 – Aggregates for Concrete| publisher = The Government of the Hong Kong Special Administrative Region | date = May 2013 }}</ref>

===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 blot]]ting 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 [[Intercalation (biochemistry)|intercalate]] in nucleic acid chains, thus avoiding interference with nucleic acid retention on hybridization membranes or with the hybridization process itself.{{Citation needed|date=January 2021}}

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|date=January 2021}}

===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 [[Ichthyophthirius multifiliis|''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".<ref>{{Cite web | title = Methylene Blue |url=https://www.3lfish.com/fish-medicants/#methylene-blue | work = 3 Little Fish Sdn Bhd |date=10 September 2021 | location = Kelana Jaya, Selangor, Malaysia }}</ref>

==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]].<ref>Heinrich Caro was an employee of the Badische Anilin- und Sodafabrik, BASF, of Mannheim, Germany, which received a patent for methylene blue in 1877:

* Badische Anilin- und Sodafabrik, BASF, of Mannheim, Germany, "Verfahren zur Darstellung blauer Farbstoffe aus Dimethylanilin und anderen tertiaren aromatischen Monaminen" [Method for preparation of blue dyes from dimethylaniline and other tertiary aromatic monoamines], Deutsches Reich Patent no. 1886 (issued: December 15, 1877).

* Available on-line at: {{cite book | vauthors = Friedlaender P |title=Fortschritte der Theerfarbenfabrikation und verwandter Industriezweige |trans-title=Progress of the manufacture of coal-tar dyes and related branches of industry |date=1888 |publisher=Julius Springer |location=Berlin, Germany |volume=1 |pages=247–249 |url=https://books.google.com/books?id=3akMAAAAYAAJ&pg=PA247 |language=German |access-date=2016-10-12 |archive-date=2015-03-21 |archive-url=https://web.archive.org/web/20150321021246/http://books.google.com/books?id=3akMAAAAYAAJ&pg=PA247 |url-status=dead }}</ref>

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.<ref>{{cite journal | vauthors = Coulibaly B, Zoungrana A, Mockenhaupt FP, Schirmer RH, Klose C, Mansmann U, Meissner PE, Müller O | display-authors = 6 | title = Strong gametocytocidal effect of methylene blue-based combination therapy against falciparum malaria: a randomised controlled trial | journal = PLOS ONE | volume = 4 | issue = 5 | pages = e5318 | year = 2009 | pmid = 19415120 | pmc = 2673582 | doi = 10.1371/journal.pone.0005318 | doi-access = free | bibcode = 2009PLoSO...4.5318C }}</ref> It was discovered to be an antidote to [[carbon monoxide poisoning]] and [[cyanide poisoning]] in 1933 by [[Matilda Moldenhauer Brooks|Matilda Brooks]].<ref>{{cite journal | doi = 10.1001/jama.1933.02740010061028| title = Methylene Blue As Antidote for Cyanide and Carbon Monoxide Poisoning| journal = JAMA| volume = 100| pages = 59| date = January 1933| vauthors = Brooks MM }}</ref>

==Names==

The [[International Nonproprietary Name]] (INN) of methylene blue is methylthioninium chloride.<ref name="pmid18037845">{{cite journal | vauthors = Adams V, Marley J, McCarroll C | title = Prilocaine induced methaemoglobinaemia in a medically compromised patient. Was this an inevitable consequence of the dose administered? | journal = British Dental Journal | volume = 203 | issue = 10 | pages = 585–587 | date = November 2007 | pmid = 18037845 | doi = 10.1038/bdj.2007.1045 | doi-access = free }}</ref><ref name="pmid16688009">{{cite journal | vauthors = Linz AJ, Greenham RK, Fallon LF | title = Methemoglobinemia: an industrial outbreak among rubber molding workers | journal = Journal of Occupational and Environmental Medicine | volume = 48 | issue = 5 | pages = 523–528 | date = May 2006 | pmid = 16688009 | doi = 10.1097/01.jom.0000201815.32098.99 | s2cid = 29264161 }}</ref>

== References ==

{{Reflist}}

== External links ==

* {{cite web | url = https://druginfo.nlm.nih.gov/drugportal/name/methylthioninium%20chloride | publisher = U.S. National Library of Medicine | work = Drug Information Portal | title = Methylene blue }}

* {{cite web | title=Methylene blue test | website=MedlinePlus | url=https://medlineplus.gov/ency/article/003412.htm }}

{{Antidotes}}

{{Stains}}

{{Glutamatergics}}

{{Monoamine metabolism modulators}}

{{Tricyclics}}

{{Portal bar|Medicine}}

{{Authority control}}

{{DEFAULTSORT:Methylene Blue}}

[[Category:Antidotes]]

[[Category:Genetics techniques]]

[[Category:Histology]]

[[Category:Redox indicators]]

[[Category:Thiazine dyes]]

[[Category:Vital stains]]

[[Category:World Health Organization essential medicines]]

[[Category:Monoamine oxidase inhibitors]]

[[Category:Phenothiazines]]

[[Category:Chlorides]]

[[Category:Wikipedia medicine articles ready to translate]]

[[Category:Dimethylamino compounds]]