Indigotindisulfonic Acid

Identification

Name
Indigotindisulfonic Acid
Accession Number
DB11577
Type
Small Molecule
Groups
Approved
Description

Indolesulfonic acid is a blue-colored dye used a marker in urological procedures, also known as indigo carmine [9].

Indigo carmine, or 5, 5'-indigodisulfonic acid sodium salt, also known as indigotine or _FD& C Blue #2 _is a pH indicator with the chemical formula C16H8N2Na2O8S2. It is approved for use as a food dye in the United States and the EU and has the E number E132 [6]

Structure
Thumb
Synonyms
  • 2-(1,3-Dihydro-3-oxo-5-sulpho-2H-indol-2-ylidene)-3-oxoindoline-5-sulphonic acid
  • 5,5'-indigotindisulfonic Acid
  • Blue X
  • Indigo carmine acid
  • indigo carmine free acid
  • indigo-5,5'-disulfonic acid
  • Indigotindisulfonate
  • Saxon blue
External IDs
NSC-8646
Product Ingredients
IngredientUNIICASInChI Key
Indigotindisulfonate sodiumD3741U8K7L860-22-0KHLVKKOJDHCJMG-QDBORUFSSA-L
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Indigo CarmineSolution0.8 %Intramuscular; IntravenousAkorn Inc1994-12-31Not applicableCanada
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Indigo CarmineIndigotindisulfonate sodium (8 mg/1mL)Injection, solutionIntramuscular; IntravenousAmerican Regent1990-09-30Not applicableUs
Indigo CarmineIndigotindisulfonate sodium (8 mg/1mL)Injection, solutionIntramuscular; IntravenousAkorn2013-03-222017-01-01Us
Indigo CarmineIndigotindisulfonate sodium (8 mg/1mL)Injection, solutionIntramuscular; IntravenousAkorn2009-04-012017-01-01Us
Categories
UNII
X7OI7JF73P
CAS number
483-20-5
Weight
Average: 422.389
Monoisotopic: 421.987856686
Chemical Formula
C16H10N2O8S2
InChI Key
CFZXDJWFRVEWSR-BUHFOSPRSA-N
InChI
InChI=1S/C16H10N2O8S2/c19-15-9-5-7(27(21,22)23)1-3-11(9)17-13(15)14-16(20)10-6-8(28(24,25)26)2-4-12(10)18-14/h1-6,17-18H,(H,21,22,23)(H,24,25,26)/b14-13+
IUPAC Name
3-oxo-2-[(2E)-3-oxo-5-sulfo-2,3-dihydro-1H-indol-2-ylidene]-2,3-dihydro-1H-indole-5-sulfonic acid
SMILES
OS(=O)(=O)C1=CC2=C(N\C(C2=O)=C2\NC3=C(C=C(C=C3)S(O)(=O)=O)C2=O)C=C1

Pharmacology

Indication

This drug was initially used as a kidney function test. The main application of indigo carmine at this time is localizing and visualizing ureteral orifices during cystoscopy and ureteral catheterization procedures [5].

Pharmacodynamics

This drug dyes tissues blue, enabling easier visualization for accuracy during medical procedures [5].

A frequently encountered cardiovascular effect of intravenous indigo carmine administration is temporary alpha-receptor stimulation. Most notably, increased total peripheral vascular resistance, diastolic and systolic blood pressure, as well as central venous pressure with decreased cardiac output, stroke volume and heart rate have been observed [1].

Mechanism of action

Indigo carmine works as a dye that accumulates in crevices, cysts, and foveolae and stains the tissue blue [13].

According to one study, the primary action of indigo carmine appears to be at the level of nitric oxide generation and/or its release from the endothelium. In addition to this, indigo carmine appears to inhibit vascular smooth muscle guanylyl cyclase. Therefore, indigo carmine may increase blood pressure by interfering with these nitric oxide-mediated vasodilatory mechanisms [2].

TargetActionsOrganism
UAryl hydrocarbon receptorNot AvailableHuman
NAlpha adrenergic receptor
agonist
Human
Absorption

Biologically inert [12].

Volume of distribution
Not Available
Protein binding
Not Available
Metabolism

Moreover, incubation of 35S-Indigo Carmine with intestinal contents of rats for 48 h suggested that isatin-5-sulphonic acid and 5-sulphoanthranilic acid may possibly be metabolites formed by intestinal bacterial metabolism of the drug. By comparison to the data obtained after intravenous administration, it was determined that the data available on the absorption, metabolism, and excretion indicated that Indigo Carmine or its metabolites were poorly absorbed [11].

Route of elimination

Indigo carmine is excreted largely by the kidneys, retaining its blue color during passage through the body.

Elimination of this dye begins rapidly after injection, appearing in the urine within 10 minutes in most cases. Larger quantities are necessary when intramuscular injection route is employed. Appearance time and elimination are delayed if given by the route of intramuscular injection [5].

Half life

4-5 minutes post-injection [5]

Clearance
Not Available
Toxicity

After intravenous administration, the LD80 was measured at 300 mg/kg in the mouse [5].

Nausea, vomiting, hypertension, bradycardia and infrequently, rash, pruritus, and bronchoconstriction. Skin discoloration may occur at high doses. Anaphylaxis is a serious adverse event that has been occasionally reported [9].

Animal studies have not been conducted with indigotindisulfonate. It is also unknown whether indigotindisulfonate sodium injection poses a risk of fetal harm when administered to a pregnant woman or whether it may affect reproduction. Indigotindisulfonate sodium injection should be given to a pregnant woman only if absolutely necessary [5].

It is not known whether this drug is excreted in human breastmilk [5].

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
AcetaminophenAcetaminophen may decrease the excretion rate of Indigotindisulfonic Acid which could result in a higher serum level.
Acetylsalicylic acidAcetylsalicylic acid may decrease the excretion rate of Indigotindisulfonic Acid which could result in a higher serum level.
AlprazolamAlprazolam may decrease the excretion rate of Indigotindisulfonic Acid which could result in a higher serum level.
AmilorideAmiloride may increase the excretion rate of Indigotindisulfonic Acid which could result in a lower serum level and potentially a reduction in efficacy.
AmitriptylineIndigotindisulfonic Acid may decrease the excretion rate of Amitriptyline which could result in a higher serum level.
AmlodipineAmlodipine may decrease the excretion rate of Indigotindisulfonic Acid which could result in a higher serum level.
AmoxicillinAmoxicillin may decrease the excretion rate of Indigotindisulfonic Acid which could result in a higher serum level.
AmphetamineAmphetamine may decrease the excretion rate of Indigotindisulfonic Acid which could result in a higher serum level.
AmpicillinAmpicillin may decrease the excretion rate of Indigotindisulfonic Acid which could result in a higher serum level.
AuranofinAuranofin may decrease the excretion rate of Indigotindisulfonic Acid which could result in a higher serum level.
Food Interactions
Not Available

References

General References
  1. Ng TY, Datta TD, Kirimli BI: Reaction to indigo carmine. J Urol. 1976 Jul;116(1):132-3. [PubMed:933277]
  2. Chang KS, Zhong MZ, Davis RF: Indigo carmine inhibits endothelium-dependent and -independent vasodilation. Hypertension. 1996 Feb;27(2):228-34. [PubMed:8567045]
  3. Grimes CL, Patankar S, Ryntz T, Philip N, Simpson K, Truong M, Young C, Advincula A, Madueke-Laveaux OS, Walters R, Ananth CV, Kim JH: Evaluating ureteral patency in the post-indigo carmine era: a randomized controlled trial. Am J Obstet Gynecol. 2017 Nov;217(5):601.e1-601.e10. doi: 10.1016/j.ajog.2017.07.012. Epub 2017 Jul 18. [PubMed:28729014]
  4. Monson FC, Wein AJ, McKenna BA, Whitmore K, Levin RM: Indigocarmine as a quantitative indicator of urothelial integrity. J Urol. 1991 Apr;145(4):842-5. [PubMed:2005716]
  5. Indigo Carmine® (indigotindisulfonate sodium injection, USP) [Link]
  6. Pub Chef, Indigo Carmine [Link]
  7. Toward an easier indigocarmine chromoendoscopy [Link]
  8. Indigo Carmine Drugs.com [Link]
  9. MIMS Indigo Carmine [Link]
  10. Indigo Carmine Daily Med [Link]
  11. Scientific Opinion on the re-evaluation of Indigo Carmine (E 132) as a food additive1 [Link]
  12. Hypotension in patients administered indigo carmine containing impurities -A case report- [Link]
  13. Indigo carmine [Link]
External Links
Human Metabolome Database
HMDB0059912
PubChem Compound
5282430
PubChem Substance
347827990
ChemSpider
4445584
ChEBI
90117
ChEMBL
CHEMBL1091250
Wikipedia
Indigo_carmine
ATC Codes
V04CH02 — Indigo carmine
MSDS
Download (48.1 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedDiagnosticColorectal Polyps1
1, 2RecruitingTreatmentBrain Tumors With Ill-defined Margins1
4CompletedTreatmentNeoplasms, Colorectal1
Not AvailableUnknown StatusDiagnosticInflammatory Bowel Diseases (IBD)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
Injection, solutionIntramuscular; Intravenous8 mg/1mL
SolutionIntramuscular; Intravenous0.8 %
Prices
Not Available
Patents
Not Available

Properties

State
Liquid
Experimental Properties
PropertyValueSource
water solubility1g/100ml MSDS
Predicted Properties
PropertyValueSource
Water Solubility0.0996 mg/mLALOGPS
logP-0.94ALOGPS
logP1.01ChemAxon
logS-3.6ALOGPS
pKa (Strongest Acidic)-2.8ChemAxon
pKa (Strongest Basic)-7.7ChemAxon
Physiological Charge-2ChemAxon
Hydrogen Acceptor Count10ChemAxon
Hydrogen Donor Count4ChemAxon
Polar Surface Area166.94 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity101.29 m3·mol-1ChemAxon
Polarizability39.65 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as indolines. These are compounds containing an indole moiety, which consists of pyrrolidine ring fused to benzene to form 2,3-dihydroindole.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Indoles and derivatives
Sub Class
Indolines
Direct Parent
Indolines
Alternative Parents
1-sulfo,2-unsubstituted aromatic compounds / Aryl ketones / Secondary alkylarylamines / Benzenoids / Vinylogous amides / Sulfonyls / Organosulfonic acids / Enamines / Azacyclic compounds / Organopnictogen compounds
show 2 more
Substituents
Arylsulfonic acid or derivatives / Dihydroindole / 1-sulfo,2-unsubstituted aromatic compound / Aryl ketone / Secondary aliphatic/aromatic amine / Benzenoid / Organic sulfonic acid or derivatives / Organosulfonic acid or derivatives / Organosulfonic acid / Sulfonyl
show 15 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Transcription regulatory region dna binding
Specific Function
Ligand-activated transcriptional activator. Binds to the XRE promoter region of genes it activates. Activates the expression of multiple phase I and II xenobiotic chemical metabolizing enzyme genes...
Gene Name
AHR
Uniprot ID
P35869
Uniprot Name
Aryl hydrocarbon receptor
Molecular Weight
96146.705 Da
References
  1. Adachi J, Mori Y, Matsui S, Takigami H, Fujino J, Kitagawa H, Miller CA 3rd, Kato T, Saeki K, Matsuda T: Indirubin and indigo are potent aryl hydrocarbon receptor ligands present in human urine. J Biol Chem. 2001 Aug 24;276(34):31475-8. Epub 2001 Jun 25. [PubMed:11425848]
  2. Peter Guengerich F, Martin MV, McCormick WA, Nguyen LP, Glover E, Bradfield CA: Aryl hydrocarbon receptor response to indigoids in vitro and in vivo. Arch Biochem Biophys. 2004 Mar 15;423(2):309-16. [PubMed:15001395]
Kind
Protein group
Organism
Human
Pharmacological action
No
Actions
Agonist
General Function
Protein heterodimerization activity
Specific Function
This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) prot...

Components:
References
  1. Hypotension in patients administered indigo carmine containing impurities -A case report- [Link]

Drug created on April 11, 2016 21:24 / Updated on August 02, 2018 07:57