Details
| Stereochemistry | ACHIRAL |
| Molecular Formula | C16H18N3S |
| Molecular Weight | 284.399 |
| Optical Activity | NONE |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Charge | 1 |
SHOW SMILES / InChI
SMILES
CN(C)C1=CC2=[S+]C3=C(C=CC(=C3)N(C)C)N=C2C=C1
InChI
InChIKey=RBTBFTRPCNLSDE-UHFFFAOYSA-N
InChI=1S/C16H18N3S/c1-18(2)11-5-7-13-15(9-11)20-16-10-12(19(3)4)6-8-14(16)17-13/h5-10H,1-4H3/q+1
| Molecular Formula | C16H18N3S |
| Molecular Weight | 284.399 |
| Charge | 1 |
| Count |
|
| Stereochemistry | ACHIRAL |
| Additional Stereochemistry | No |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Optical Activity | NONE |
DescriptionCurator's Comment: http://www.mdpoison.com/media/SOP/mdpoisoncom/healthcareprofessionals/antidote-facts/Methylene%20Blue%20Antidote%20Facts.pdf |
https://clinicaltrials.gov/ct2/show/NCT01797978 | https://www.pharmgkb.org/pathway/PA165980834
Curator's Comment: http://www.mdpoison.com/media/SOP/mdpoisoncom/healthcareprofessionals/antidote-facts/Methylene%20Blue%20Antidote%20Facts.pdf |
https://clinicaltrials.gov/ct2/show/NCT01797978 | https://www.pharmgkb.org/pathway/PA165980834
Methylene blue, also known as methylthioninium chloride, is a medication from WHO's list of essential medicines. Upon administration, methylene blue is converted to leukomethylene blue by erythrocyte methemoblobin reductase in the presence of NADPH. Leukomethylene blue than reduces methemoglobin to oxyhemoglobin, thus restoring oxygen carrying capacity of the blood. Methylene blue is also used as a dye for various diagnostic procedures, for treatment of ifosfamide toxicity and for in vitro staining. Historically, it was used as a photosensitizer for photodynamic therapy for topical treatment of dermatologic or mucocutaneous infections, as an antidote for cyanide poisoning, but these applications are no longer approved. Methylene blue is investigated in clinical trials for treatment of septic shock and Alzheimer's disease.
Approval Year
Targets
| Primary Target | Pharmacology | Condition | Potency |
|---|---|---|---|
Target ID: P00387|||Q9UL55 Gene ID: 1727.0 Gene Symbol: CYB5R3 Target Organism: Homo sapiens (Human) |
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Target ID: CHEMBL2111350 |
5.3 µM [IC50] |
Conditions
| Condition | Modality | Targets | Highest Phase | Product |
|---|---|---|---|---|
| Primary | METHYLENE BLUE Approved UseUsed for methemoglobinemia associated with certain drugs (e.g., dapsone, benzocaine, lidocaine), occupational or other exposures to toxic chemicals (e.g., hydrazine, amine-substituted benzenes, nitro-substituted benzenes, nitrates, nitrites), or substance abuse (e.g., inhalation or ingestion of volatile nitrites). |
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| Primary | METHYLENE BLUE Approved UseManagement of ifosfamide-induced encephalopathy |
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| Diagnostic | METHYLENE BLUE Approved UseHas been used as diagnostic (visualizing) dye in a variety of procedures, including sentinel lymph node biopsy in cancer patients (e.g., breast cancer patients), endoscopic evaluation of lesions in patients with GERD or Barrett's esophagus, urologic evaluation in patients with ureteral or renal pelvis injury, and thoroscopic procedures in patients with pulmonary nodules. |
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| Primary | METHYLENE BLUE Approved UseHas been used as a photosensitizer for photodynamic therapy for topical treatment of dermatologic or mucocutaneous infections (e.g., herpes labialis, eczema herpeticum, oral candidiasis, cutaneous leishmaniasis, chromoblastomycosis) or chronic dermatologic or mucocutaneous conditions (e.g., plaque psoriasis, oral lichen planus). |
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| Primary | Unknown Approved UseUnknown |
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| Preventing | Unknown Approved UseUnknown |
Cmax
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
2917 ng/mL |
2 mg/kg single, intravenous dose: 2 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered: |
METHYLENE BLUE plasma | Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
|
8 μM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10952480/ |
100 mg single, intravenous dose: 100 mg route of administration: Intravenous experiment type: SINGLE co-administered: |
METHYLENE BLUE plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
AUC
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
13977 ng × h/mL |
2 mg/kg single, intravenous dose: 2 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered: |
METHYLENE BLUE plasma | Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
|
134 μM × min EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10952480/ |
100 mg single, intravenous dose: 100 mg route of administration: Intravenous experiment type: SINGLE co-administered: |
METHYLENE BLUE plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
T1/2
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
24 h |
2 mg/kg single, intravenous dose: 2 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered: |
METHYLENE BLUE plasma | Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
|
6.6 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10952480/ |
100 mg single, intravenous dose: 100 mg route of administration: Intravenous experiment type: SINGLE co-administered: |
METHYLENE BLUE plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
Funbound
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
6% |
2 mg/kg single, intravenous dose: 2 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered: |
METHYLENE BLUE plasma | Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
Doses
| Dose | Population | Adverse events |
|---|---|---|
72 mg/kg 4 times / day multiple, intravenous (total) Highest studied dose Dose: 72 mg/kg, 4 times / day Route: intravenous Route: multiple Dose: 72 mg/kg, 4 times / day Co-administed with:: chloroquine, p.o(10 mg/kg on days 0 and 1, and 5 mg/kg on day 2) Sources: Page: p.3 |
unhealthy, 0.5-4.9 n = 123 Health Status: unhealthy Condition: Malaria Age Group: 0.5-4.9 Sex: M+F Population Size: 123 Sources: Page: p.3 |
Other AEs: Anemia... |
1 g single, intravenous Overdose |
healthy, 3 n = 1 Health Status: healthy Age Group: 3 Sex: M Population Size: 1 Sources: |
Disc. AE: Tachycardia, Cyanosis... AEs leading to discontinuation/dose reduction: Tachycardia Sources: Cyanosis |
AEs
| AE | Significance | Dose | Population |
|---|---|---|---|
| Anemia | 0.8% | 72 mg/kg 4 times / day multiple, intravenous (total) Highest studied dose Dose: 72 mg/kg, 4 times / day Route: intravenous Route: multiple Dose: 72 mg/kg, 4 times / day Co-administed with:: chloroquine, p.o(10 mg/kg on days 0 and 1, and 5 mg/kg on day 2) Sources: Page: p.3 |
unhealthy, 0.5-4.9 n = 123 Health Status: unhealthy Condition: Malaria Age Group: 0.5-4.9 Sex: M+F Population Size: 123 Sources: Page: p.3 |
| Cyanosis | Disc. AE | 1 g single, intravenous Overdose |
healthy, 3 n = 1 Health Status: healthy Age Group: 3 Sex: M Population Size: 1 Sources: |
| Tachycardia | Disc. AE | 1 g single, intravenous Overdose |
healthy, 3 n = 1 Health Status: healthy Age Group: 3 Sex: M Population Size: 1 Sources: |
PubMed
| Title | Date | PubMed |
|---|---|---|
| Acquired methemoglobinemia and hemolytic anemia after usual doses of phenazopyridine. | 1982 Feb |
|
| Cardiovascular depressant effects of N-methyl- and N-isobutyl-1,2-diphenyl ethanolamines: elucidation of the mechanisms of action. | 1991 Jan-Feb |
|
| Neurotoxicity in conscious rats following intraventricular SNAP, a nitric oxide donor. | 1994 Jul |
|
| Multifactorial mediation of post norepinephrine induced intestinal hyperemia. | 1994 Jun |
|
| Toxic oil stimulates collagen synthesis acting at a pretranslational level in cultured fat-storing cells. | 1994 Mar |
|
| Nitric oxide is a central mediator of penile erection. | 1994 Nov |
|
| [Treatment of ifosfamide induced encephalopathy with methylene-blue]. | 1995 Jul |
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| Methylene blue for ifosfamide-associated encephalopathy. | 1995 May 4 |
|
| Methylene blue and the neurotoxic mechanisms of ifosfamide encephalopathy. | 1996 |
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| [Successful treatment with methylene blue of ifosfamide-induced central nervous system effects]. | 1996 Apr 26 |
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| Ifosfamide encephalopathy and methylene-blue: a case report. | 1996 Aug |
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| Alternative approaches to the management of priapism. | 1998 Mar |
|
| Spinal antinociceptive effect of epidural nonsteroidal antiinflammatory drugs on nitric oxide-induced hyperalgesia in rats. | 1999 Jul |
|
| Methylene blue in the treatment and prevention of ifosfamide-induced encephalopathy: report of 12 cases and a review of the literature. | 2000 Jan |
|
| Ifosfamide induced encephalopathy following chemotherapy of Non-Hodgkin's Lymphoma. | 2001 Dec |
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| Improvement of preservation with cardioplegic solution by nitroglycerin-induced delayed preconditioning is mediated by calcitonin gene-related peptide. | 2001 Dec |
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| Severe methemoglobinemia from topical anesthetic spray: case report, discussion and qualitative systematic review. | 2001 Jan |
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| Delayed cardioprotection induced by nitroglycerin is mediated by alpha-calcitonin gene-related peptide. | 2002 Apr |
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| Methylene blue: the drug of choice for catecholamine-refractory vasoplegia after cardiopulmonary bypass? | 2003 Jun |
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| Ifosfamide-induced encephalopathy with or without using methylene blue. | 2005 Sep-Oct |
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| [Ifosfamide induced encephalopathy: 15 observations]. | 2006 Feb |
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| Methemoglobinemia-induced cardio-respiratory failure secondary to topical anesthesia. | 2006 Nov-Dec |
|
| Effect of manganese on luteinizing hormone-releasing hormone secretion in adult male rats. | 2007 May |
|
| Inhibition of the bioactivation of the neurotoxin MPTP by antioxidants, redox agents and monoamine oxidase inhibitors. | 2011 Aug |
|
| The specific interaction of the photosensitizer methylene blue with acetylcholinesterase provides a model system for studying the molecular consequences of photodynamic therapy. | 2013 Mar 25 |
|
| FDA-approved drugs and other compounds tested as inhibitors of human glutathione transferase P1-1. | 2013 Sep 5 |
Patents
Sample Use Guides
Main route of adminitration is intravenous, 1-2 mg/kg by slow IV injection. Inject slowly over several minutes (usually 3–10 minutes). Historically was also administered orally, but oral preparations are no longer commercially available in US. As a photosensitizer is administered topically. For a diagnostic purposes is administered by local instillation or injection.
Route of Administration:
Other
Suspension of erytrocytes from acid/citrate/dextrose-treated blood were incubabed on air with 0.5M M-sodium nitrite solution in isoosmotic saline. The erytrocytes were separated by centrifugation, washed, and incubated at pH 7.4 and 37°C with 10 mM glucose and 10 uM Methylene Blue. Samples were taken at defined intervals and hemolysed with 10 vol of ice-cold water, after that the content of mehtemoglobin, hemoglobins intermediate and oxyhemoglobin was estimated.
| Substance Class |
Chemical
Created
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| Record UNII |
ZMZ79891ZH
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| Record Status |
Validated (UNII)
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Systematic Name | English |
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EU-Orphan Drug |
EU/3/10/807
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WHO-ATC |
V04CG05
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N0000192516
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WHO-ATC |
V03AB17
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1546414
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SUB03262MIG
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N0000175545
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PRIMARY | Oxidation-Reduction Activity [MoA] |
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SALT/SOLVATE -> PARENT |
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SALT/SOLVATE -> PARENT |
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SALT/SOLVATE -> PARENT | |||
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TARGET -> SUBSTRATE |
Converts Ferric ion to Ferrous Ion in Methemoglobin
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SALT/SOLVATE -> PARENT |
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SALT/SOLVATE -> PARENT |
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METABOLITE -> PARENT |
Maybe non-enzymatic reversible. Predominant metabolite in urine.
URINE
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ACTIVE MOIETY |
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