METHYLENE BLUE CATION

First marketed in 1921

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

Structure Search

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

HIDE SMILES / InChI

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
Sources: https://www.drugs.com/monograph/methylene-blue.html
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

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
NADH-cytochrome b5 reductase 3 6 Target ID: P00387\|\|\|Q9UL55 Gene ID: 1727.0 Gene Symbol: CYB5R3 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/7396878	Substrate 661
Nitric oxide synthase (inducible and endothelial) 9 Target ID: CHEMBL2111350 Sources: https://www.ncbi.nlm.nih.gov/pubmed/7679577	Inhibitor 8297		5.3 µM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Methemoglobinemia 6 Sources: https://www.drugs.com/monograph/methylene-blue.html	Primary	Approved 8429	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).
Ifosfamide-induced encelophaty 6 Sources: https://www.drugs.com/monograph/methylene-blue.html	Primary	Approved 8429	METHYLENE BLUE Approved Use Management of ifosfamide-induced encephalopathy
Cancer 592 Sources: https://www.drugs.com/monograph/methylene-blue.html	Diagnostic	Approved 8429	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.
Dermatologic infections 6 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25048768	Primary	Approved 8429	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).
Septic shock 21 Sources: https://clinicaltrials.gov/ct2/show/NCT01797978	Primary	Phase III 656	Unknown Approved Use Unknown
Alzheimer’s disease 272 Sources: https://clinicaltrials.gov/ct2/show/NCT02380573	Preventing	Phase II 1132	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
2917 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/204630s006lbl.pdf	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 DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/204630s006lbl.pdf	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

T_1/2

Value	Dose	Co-administered	Analyte	Population
24 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/204630s006lbl.pdf	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

F_unbound

Value	Dose	Co-administered	Analyte	Population
6% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/204630s006lbl.pdf	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: https://pubmed.ncbi.nlm.nih.gov/17026773 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: https://pubmed.ncbi.nlm.nih.gov/17026773 Page: p.3	Other AEs: Anemia... Other AEs: Anemia (0.8%) Sources: https://pubmed.ncbi.nlm.nih.gov/17026773 Page: p.3
1 g single, intravenous Overdose Dose: 1 g Route: intravenous Route: single Dose: 1 g Sources: https://pubmed.ncbi.nlm.nih.gov/973698	healthy, 3 n = 1 Health Status: healthy Age Group: 3 Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/973698	Disc. AE: Tachycardia, Cyanosis... AEs leading to discontinuation/dose reduction: Tachycardia Cyanosis Sources: https://pubmed.ncbi.nlm.nih.gov/973698

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: https://pubmed.ncbi.nlm.nih.gov/17026773 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: https://pubmed.ncbi.nlm.nih.gov/17026773 Page: p.3
Cyanosis	Disc. AE	1 g single, intravenous Overdose Dose: 1 g Route: intravenous Route: single Dose: 1 g Sources: https://pubmed.ncbi.nlm.nih.gov/973698	healthy, 3 n = 1 Health Status: healthy Age Group: 3 Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/973698
Tachycardia	Disc. AE	1 g single, intravenous Overdose Dose: 1 g Route: intravenous Route: single Dose: 1 g Sources: https://pubmed.ncbi.nlm.nih.gov/973698	healthy, 3 n = 1 Health Status: healthy Age Group: 3 Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/973698

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P000KBE
1PlusChem LLC	1P0035Q5
1PlusChem LLC	1P00IKXL
A2B Chem	AI66137
AA Blocks	AA00IKE5
AAA Chemistry	AR-1K4257
ABI Chem	AC1L1HI1
ABI Chem	AC1Q4UZ6
AK Scientific	6335AF
AK Scientific	6336AF
AK Scientific	6337AF
AK Scientific	6338AF
AbovChem LLC	HY-14536
Acros Organics	12675
Acros Organics	22980
Acros Organics	41424
Acros Organics	41425
Alfa Chemistry	42771
Alfa Chemistry	A18174
Alfa Chemistry	ACM61734
Alfa Chemistry	ACM7220793
Alfa Chemistry	J60823
Alinda	IBS-E0000554
Ambinter	Amb19654466	http://www.ambinter.com/reference/19654466
Ambinter	Amb21855833	http://www.ambinter.com/reference/21855833
Angene	AGN-PC-0O0J7Q
Angene	AGN-PC-0OH2YS
Apollo Scientific	BIA4084
Aronis	M04821
AstaTech	43008
Aurora Fine Chemicals LLC	A12.866.455	http://online.aurorafinechemicals.com/info?ID=A12.866.455
BLD Pharm	BD139888
BLD Pharm	BD305948
BLD Pharm	BD338910
BOC Sciences	122965-43-9
BOC Sciences	26283-09-0
BOC Sciences	37247-10-2
BOC Sciences	61-73-4
BOC Sciences	7220-79-3
BioSynth	M-3598
Bosche Scientific	M2940
Bosche Scientific	M2943
Capot Chemical	35596
Chem Scene	CS-0013101
Chem Scene	CS-2959
Chem-Impex International	210
Chem-Impex International	22930
ChemDiv	0083-0118
ChemShuttle	141809
Chemspace	CSSS00160696622	https://chem-space.com/CSSS00160696622
Compound Cloud	104827
Compound Cloud	16211647
Compound Cloud	4139
Compound Cloud	6099
DC Chemicals	DC11091	http://www.dcchemicals.com/product_show-DC11091.html
Enamine	EN300-6504462
Fluorochem	468422
Fluorochem	492385
Hairui	HR144947
Hangzhou APIChem Technology	AC-15225
Hangzhou APIChem Technology	AC-8349
Hangzhou Yuhao Chemical Technology	HL3337
Hangzhou Yuhao Chemical Technology	JZ4569
Hangzhou Yuhao Chemical Technology	LT7437
Hangzhou Yuhao Chemical Technology	XJ6809
Hangzhou Yuhao Chemical Technology	YH15655
KeyOrganics	AS-35256
Lab Network	33
Lab Network	LN00193772
Lab Network	LN00194290
Lab Network	LN00237724
Lab Network	LN02135350
MedChem Express	HY-14536
MedChem Express	HY-B1359
MolPort	MolPort-001-494-481
MolPort	MolPort-003-666-690
MolPort	MolPort-004-963-308
MolPort	MolPort-006-110-157
MolPort	MolPort-039-063-118
Molnova	M15760
Molnova	M18906
MuseChem	A000087
MuseChem	M057779
MuseChem	M060342
MuseChem	R037152
MuseChem	R045681
NCI Plated 2007	215213
NCI Plated 2007	3089
NCI Plated 2007	617593
Ryan Scientific	Diolane
Scientific Exchange	R-079267
Selleck Chemicals	S4535
Sigma Aldrich	66725
Sigma Aldrich	M1800900
Sigma Aldrich	M44907
Sigma Aldrich	M9140\|SIAL
Sigma Aldrich	MB1
Smolecule	S564122	https://www.smolecule.com/products/s564122
TargetMol	T0006
TargetMol	T6888
Tetrahedron	TS78351
Tetrahedron	TS80135
TimTec	SBB060907
TimTec	ST093058
TimTec	ST50406156
TimTec	ST50406802
TimTec	ST50411628
Tocris	3213
Vitas-M Laboratory	STL483851	http://www.request.vitasmlab.com/index.php?option=com_search_stk&Itemid=22&stk=STL483851&?utm_source=pubchem&utm_medium=p_search_link&utm_campaign=pubchem_search&utm_content=pubchem_slink
W&J PharmaChem	50C912420
Yuhao Chemical	LT7437	http://www.chemyuhao.com/61-73-4.html
ZINC	ZINC000012414057	http://zinc15.docking.org/substances/ZINC000012414057
eMolecules	207322640
eMolecules	271447134
eMolecules	28206441
eMolecules	56968286
eMolecules	66729975
eNovation Chemicals	D329417
eNovation Chemicals	D394566
mcule	MCULE-6490213141	https://mcule.com/MCULE-6490213141/

PubMed

Title	Date	PubMed
Cardiovascular depressant effects of N-methyl- and N-isobutyl-1,2-diphenyl ethanolamines: elucidation of the mechanisms of action.	1991 Jan-Feb	1888233
Multifactorial mediation of post norepinephrine induced intestinal hyperemia.	1994 Jun	7949234
[Treatment of ifosfamide induced encephalopathy with methylene-blue].	1995 Jul	7549123
[Successful treatment with methylene blue of ifosfamide-induced central nervous system effects].	1996 Apr 26	8620831
Spinal antinociceptive effect of epidural nonsteroidal antiinflammatory drugs on nitric oxide-induced hyperalgesia in rats.	1999 Jul	10422945
Ifosfamide induced encephalopathy following chemotherapy of Non-Hodgkin's Lymphoma.	2001 Dec	11799423
Delayed cardioprotection induced by nitroglycerin is mediated by alpha-calcitonin gene-related peptide.	2002 Apr	11919648
Evaluating risk factors for the development of ifosfamide encephalopathy.	2005 Jun	15923801
Ifosfamide-induced encephalopathy with or without using methylene blue.	2005 Sep-Oct	16174228
Methemoglobinemia-induced cardio-respiratory failure secondary to topical anesthesia.	2006 Nov-Dec	17122537
Ifosfamide-related encephalopathy in elderly patients : report of five cases and review of the literature.	2007	17953463
Effect of manganese on luteinizing hormone-releasing hormone secretion in adult male rats.	2007 May	17290048
Methylthioninium chloride reverses cognitive deficits induced by scopolamine: comparison with rivastigmine.	2009 Jan	19005644
Inhibition of the bioactivation of the neurotoxin MPTP by antioxidants, redox agents and monoamine oxidase inhibitors.	2011 Aug	21554916
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	23159732
FDA-approved drugs and other compounds tested as inhibitors of human glutathione transferase P1-1.	2013 Sep 5	23769903

Patents

Sample Use Guides

In Vivo Use Guide

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 21:15:39 GMT 2023` Edited by `admin` on `Fri Dec 15 21:15:39 GMT 2023`
Record UNII	ZMZ79891ZH
Record Status	`Validated (UNII)`
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Name

Type

Language

METHYLENE BLUE CATION

Common Name

English

METHYLTHIONINIUM

Systematic Name

English

Methylthioninium [WHO-DD]

Common Name

English

PHENOTHIAZIN-5-IUM, 3,7-BIS(DIMETHYLAMINO)-

Systematic Name

English

Classification Tree Code System Code

EU-Orphan Drug

EU/3/10/807