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Details

Stereochemistry ACHIRAL
Molecular Formula C16H18N3S.Cl.3H2O
Molecular Weight 373.898
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of METHYLENE BLUE

SMILES

O.O.O.[Cl-].CN(C)C1=CC2=[S+]C3=C(C=CC(=C3)N(C)C)N=C2C=C1

InChI

InChIKey=XQAXGZLFSSPBMK-UHFFFAOYSA-M
InChI=1S/C16H18N3S.ClH.3H2O/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;1H;3*1H2/q+1;;;;/p-1

HIDE SMILES / InChI

Molecular Formula H2O
Molecular Weight 18.0153
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Molecular Formula ClH
Molecular Weight 36.461
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

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

Description
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.

CNS Activity

Curator's Comment: When injected intraperitoneally into live rats, MB crosses the blood-brain barrier and selectively stains brain tissueand selectively stains brain tissue.

Originator

Curator's Comment: Methylene blue was first prepared in 1876 by Heinrich Caro at BASF.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Target ID: P00387|||Q9UL55
Gene ID: 1727.0
Gene Symbol: CYB5R3
Target Organism: Homo sapiens (Human)
5.3 µM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
METHYLENE BLUE

Approved Use

Used 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).
Primary
METHYLENE BLUE

Approved Use

Management of ifosfamide-induced encephalopathy
Diagnostic
METHYLENE BLUE

Approved Use

Has 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.
Primary
METHYLENE BLUE

Approved Use

Has 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).
Primary
Unknown

Approved Use

Unknown
Preventing
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
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
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

AUC

ValueDoseCo-administeredAnalytePopulation
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
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

T1/2

ValueDoseCo-administeredAnalytePopulation
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
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

Funbound

ValueDoseCo-administeredAnalytePopulation
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

Doses

DosePopulationAdverse 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...
Other AEs:
Anemia (0.8%)
Sources: Page: p.3
1 g single, intravenous
Overdose
Dose: 1 g
Route: intravenous
Route: single
Dose: 1 g
Sources:
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
Cyanosis
Sources:
AEs

AEs

AESignificanceDosePopulation
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
Dose: 1 g
Route: intravenous
Route: single
Dose: 1 g
Sources:
healthy, 3
n = 1
Health Status: healthy
Age Group: 3
Sex: M
Population Size: 1
Sources:
Tachycardia Disc. AE
1 g single, intravenous
Overdose
Dose: 1 g
Route: intravenous
Route: single
Dose: 1 g
Sources:
healthy, 3
n = 1
Health Status: healthy
Age Group: 3
Sex: M
Population Size: 1
Sources:
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Acquired methemoglobinemia and hemolytic anemia after usual doses of phenazopyridine.
1982 Feb
Neurotoxicity in conscious rats following intraventricular SNAP, a nitric oxide donor.
1994 Jul
Prevention by NG-nitro-L-arginine methyl ester of apomorphine- and oxytocin-induced penile erection and yawning: site of action in the brain.
1994 Jul
Multifactorial mediation of post norepinephrine induced intestinal hyperemia.
1994 Jun
Methylene blue for ifosfamide-associated encephalopathy.
1995 May 4
[Successful treatment with methylene blue of ifosfamide-induced central nervous system effects].
1996 Apr 26
Alternative approaches to the management of priapism.
1998 Mar
[The enhancement of formalin induced agitation behavior by intrathecal administration of prostaglandin E1].
1999 Aug
Spinal antinociceptive effect of epidural nonsteroidal antiinflammatory drugs on nitric oxide-induced hyperalgesia in rats.
1999 Jul
Improvement of preservation with cardioplegic solution by nitroglycerin-induced delayed preconditioning is mediated by calcitonin gene-related peptide.
2001 Dec
Delayed cardioprotection induced by nitroglycerin is mediated by alpha-calcitonin gene-related peptide.
2002 Apr
Methylene blue for lithium-induced refractory hypotension in off-pump coronary artery bypass graft: report of two cases.
2004 Feb
Evaluating risk factors for the development of ifosfamide encephalopathy.
2005 Jun
Ifosfamide encephalopathy: a case report.
2005 Mar-Apr
Ifosfamide-induced encephalopathy with or without using methylene blue.
2005 Sep-Oct
[Ifosfamide induced encephalopathy: 15 observations].
2006 Feb
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
Methylene blue provides behavioral and metabolic neuroprotection against optic neuropathy.
2009 Apr
Dual action of phenylarsine oxide on the glucose transport activity of GLUT1.
2009 Dec 10
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
In Vitro Use Guide
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
by admin
on Fri Dec 15 15:03:25 UTC 2023
Edited
by admin
on Fri Dec 15 15:03:25 UTC 2023
Record UNII
T42P99266K
Record Status Validated (UNII)
Record Version
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Name Type Language
METHYLENE BLUE
HPUS   II   USP   VANDF  
Common Name English
NSC-759135
Code English
METHYLENE BLUE [HPUS]
Common Name English
METHYLENE BLUE TRIHYDRATE
MI  
Common Name English
METHYLENE BLUE [ORANGE BOOK]
Common Name English
METHYLENE BLUE [USP MONOGRAPH]
Common Name English
TETRAMETHYLTHIONINE CHLORIDE TRIHYDRATE
Systematic Name English
METHYLENE BLUE [VANDF]
Common Name English
METHYLTHIONINIUM CHLORIDE TRIHYDRATE [WHO-IP]
Common Name English
PROVAYBLUE
Brand Name English
METHYLENE BLUE TRIHYDRATE [MI]
Common Name English
BASIC BLUE 9 TRIHYDRATE
Common Name English
METHYLTHIONINIUM CHLORIDE TRIHYDRATE
WHO-IP  
Systematic Name English
METHYLENE BLUE [IARC]
Common Name English
METHYLTHIONINII CHLORIDUM TRIHYDRATE [WHO-IP LATIN]
Common Name English
C.I. BASIC BLUE 9 TRIHYDRATE
Common Name English
METHYLENE BLUE [II]
Common Name English
PHENOTHIAZIN-5-IUM, 3,7-BIS(DIMETHYLAMINO)-, CHLORIDE, TRIHYDRATE
Systematic Name English
METHYLENE BLUE [USP-RS]
Common Name English
Classification Tree Code System Code
FDA ORPHAN DRUG 345711
Created by admin on Fri Dec 15 15:03:25 UTC 2023 , Edited by admin on Fri Dec 15 15:03:25 UTC 2023
EPA PESTICIDE CODE 39505
Created by admin on Fri Dec 15 15:03:25 UTC 2023 , Edited by admin on Fri Dec 15 15:03:25 UTC 2023
NCI_THESAURUS C461
Created by admin on Fri Dec 15 15:03:25 UTC 2023 , Edited by admin on Fri Dec 15 15:03:25 UTC 2023
FDA ORPHAN DRUG 385512
Created by admin on Fri Dec 15 15:03:25 UTC 2023 , Edited by admin on Fri Dec 15 15:03:25 UTC 2023
FDA ORPHAN DRUG 357111
Created by admin on Fri Dec 15 15:03:25 UTC 2023 , Edited by admin on Fri Dec 15 15:03:25 UTC 2023
Code System Code Type Description
WIKIPEDIA
METHYLENE BLUE
Created by admin on Fri Dec 15 15:03:25 UTC 2023 , Edited by admin on Fri Dec 15 15:03:25 UTC 2023
PRIMARY
ChEMBL
CHEMBL191083
Created by admin on Fri Dec 15 15:03:25 UTC 2023 , Edited by admin on Fri Dec 15 15:03:25 UTC 2023
PRIMARY
FDA UNII
T42P99266K
Created by admin on Fri Dec 15 15:03:25 UTC 2023 , Edited by admin on Fri Dec 15 15:03:25 UTC 2023
PRIMARY
RXCUI
6878
Created by admin on Fri Dec 15 15:03:25 UTC 2023 , Edited by admin on Fri Dec 15 15:03:25 UTC 2023
PRIMARY RxNorm
CAS
122965-43-9
Created by admin on Fri Dec 15 15:03:25 UTC 2023 , Edited by admin on Fri Dec 15 15:03:25 UTC 2023
NON-SPECIFIC STOICHIOMETRY
MESH
D008751
Created by admin on Fri Dec 15 15:03:25 UTC 2023 , Edited by admin on Fri Dec 15 15:03:25 UTC 2023
PRIMARY
EPA CompTox
DTXSID0025600
Created by admin on Fri Dec 15 15:03:25 UTC 2023 , Edited by admin on Fri Dec 15 15:03:25 UTC 2023
PRIMARY
RS_ITEM_NUM
1428008
Created by admin on Fri Dec 15 15:03:25 UTC 2023 , Edited by admin on Fri Dec 15 15:03:25 UTC 2023
PRIMARY
CHEBI
6872
Created by admin on Fri Dec 15 15:03:25 UTC 2023 , Edited by admin on Fri Dec 15 15:03:25 UTC 2023
PRIMARY
DRUG BANK
DB09241
Created by admin on Fri Dec 15 15:03:25 UTC 2023 , Edited by admin on Fri Dec 15 15:03:25 UTC 2023
PRIMARY
CAS
7220-79-3
Created by admin on Fri Dec 15 15:03:25 UTC 2023 , Edited by admin on Fri Dec 15 15:03:25 UTC 2023
PRIMARY
NCI_THESAURUS
C644
Created by admin on Fri Dec 15 15:03:25 UTC 2023 , Edited by admin on Fri Dec 15 15:03:25 UTC 2023
PRIMARY
EVMPD
SUB08877MIG
Created by admin on Fri Dec 15 15:03:25 UTC 2023 , Edited by admin on Fri Dec 15 15:03:25 UTC 2023
PRIMARY
DAILYMED
T42P99266K
Created by admin on Fri Dec 15 15:03:25 UTC 2023 , Edited by admin on Fri Dec 15 15:03:25 UTC 2023
PRIMARY
MERCK INDEX
m7402
Created by admin on Fri Dec 15 15:03:25 UTC 2023 , Edited by admin on Fri Dec 15 15:03:25 UTC 2023
PRIMARY Merck Index
NSC
759135
Created by admin on Fri Dec 15 15:03:25 UTC 2023 , Edited by admin on Fri Dec 15 15:03:25 UTC 2023
PRIMARY
WHO INTERNATIONAL PHARMACOPEIA
METHYLENE BLUE
Created by admin on Fri Dec 15 15:03:25 UTC 2023 , Edited by admin on Fri Dec 15 15:03:25 UTC 2023
PRIMARY Other name: Methylene blue.Description: Dark green crystals with a metallic lustre or a dark green, crystalline powder; odourless or almost odourless. Solubility: Sparingly soluble in water; slightly soluble in ethanol (~750 g/l) TS; practically insoluble in ether R. Category: Antidote. Storage: Methylthioninium chloride should be kept in a tightly closed container, protected from light. Additional information: Methylthioninium chloride is hygroscopic. Definition: Methylthioninium chloride contains not less than 97.0% and not more than 101.0% of C16H18ClN3S, calculated with reference to the dried substance.
PUBCHEM
104827
Created by admin on Fri Dec 15 15:03:25 UTC 2023 , Edited by admin on Fri Dec 15 15:03:25 UTC 2023
PRIMARY
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PARENT -> SALT/SOLVATE
ANHYDROUS->SOLVATE
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IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
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IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
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ACTIVE MOIETY