Carbazochrome

Identification

Name
Carbazochrome
Accession Number
DB09012
Type
Small Molecule
Groups
Experimental, Withdrawn
Description

Carbazochrome is a hemostatic agent that causes the aggregation and adhesion of platelets in the blood to form a platelet plug, ceasing blood flow from an open wound. It is an oxidation product of adrenaline which enhances the microcirculatory tone [4]. It is hoped that this drug can be used in the future for preventing excessive blood flow during surgical operations and the treatment of hemorrhoids, but research on its effectiveness and the severity of possible side effects remains to be fairly inconclusive. It is not FDA-approved but is available as tablets or IM/SC injections in the treatment of hemorrhages in a number of countries.

Carbazochrome has been investigated for use in the treatment of non-surgical acute uncomplicated hemorrhoids in a mixture with Troxerutin, and this combination therapy demonstrated efficacy and safe tolerability either at a local or systemic level [1].

Structure
Thumb
Synonyms
  • 3-Hydroxy-1-methyl-5,6-inodlindionsemicarbazon
  • Adchnon
  • Adedolon
  • Adrenostan
  • Carbazochrom
  • Carbazochromum
  • Carbazocromo
  • EINECS 200-717-0
  • NSC 73742
International/Other Brands
Adcar AC (Nisshin Pharmaceutical) / Adona (Tanabe) / Adonamin (Towa Yakuhin) / Adrenochrome (Quality Pharm) / Adrenoxil (Climax,) / Adrome (Landson) / Almetex (Alkaloid) / Anaroxyl (Organon) / Auzei (Nichi-Iko Pharmaceutical) / Carbajust (Yoshindo) / Chichina (Fuso Pharmaceutical) / Chromazol (Solas) / Crome (Ferron) / Cromin's (Infarmasa) / Di Ka Ning (Bosen Bio Pharmaceutical) / Fleboside (Acarpia-P) / Fleboton (Minapharm) / Ge Dan (Changfu Jiejing Pharmaceutical) / Hemosin K (Hormona) / Le Ka Ning (Pude) / Le Zhi Na (Tai'an Pharmaceutical Factory) / Luoye (Suzhou No.6) / Na Neng (Double-Crane) / Odanon (Towa Yakuhin) / Ophthalm K (Alfresa Pharma) / Ranobi (Koa Isei) / Styptochrome (Dr. Reddy's) / Su Bo Te (Laien Pharmaceutical) / Tai Si Neng (Tide Pharmaceutical) / Toxivenol (Kleva) / Velchrome (Novell Pharmaceutical) / Xue Yi Ting (Weifang Pharmaceutical Factory)
Categories
UNII
81F061RQS4
CAS number
69-81-8
Weight
Average: 236.231
Monoisotopic: 236.090940262
Chemical Formula
C10H12N4O3
InChI Key
XSXCZNVKFKNLPR-SDQBBNPISA-N
InChI
InChI=1S/C10H12N4O3/c1-14-4-9(16)5-2-6(12-13-10(11)17)8(15)3-7(5)14/h2-3,9,16H,4H2,1H3,(H3,11,13,17)/b12-6-
IUPAC Name
{[(5Z)-3-hydroxy-1-methyl-6-oxo-2,3,5,6-tetrahydro-1H-indol-5-ylidene]amino}urea
SMILES
CN1CC(O)C2=C\C(=N\NC(N)=O)C(=O)C=C12

Pharmacology

Indication

Indicated for capillary and parenchymal hemorrhage (trauma, tonsillectomy, during surgery), intestinal bleeding, and thrombocytopenic purpura.

Pharmacodynamics

Carbazochrome is an anti-bleeding agent that increases platelet aggregation and forms a platelet plug by interacting with α-adrenoreceptors on surface of platelets [5]. It is shown to improve the structure of local capillary vessels in haemorrhage caused by fragility of capillaries. Carbazochrome capillary stabilizer that reverses pulmonary vascular hyperpermeability and decreases arterial PaO2 in experimental models [3].

Mechanism of action

Carbazochrome interacts with platelet surface α-adrenoreceptors which are Gq-coupled receptors that leads to activation of PLC IP3/DAG pathway and increase in intracellular calcium levels. Elevated calcium ions bind to calmodulin and activates Ca2+/calmodulin-dependent myosin light chain kinase, allowing the myosin crossbridge to bind to the actin filament and polymerisation of globular actin (G-actin) to filamentous actin (F-actin) [2]. Subsequent contraction of endothelial cells changes the shape of platelets and promotes the release of factors such as serotonin, ADP, Von Willebrand and platelet activating factor by platelets that induce aggregation and platelet adherence [5]. Carbazochrome is reported to inhibit vascular hyperpermeability by inhibiting agonist-induced phosphoinositides hydrolysis caused by various vasoactive agents such as tryptase, thrombin and bradykinin [2].

Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

General References
  1. Squadrito F, Altavilla D, Oliaro Bosso S: Double-blind, randomized clinical trial of troxerutin-carbazochrome in patients with hemorrhoids. Eur Rev Med Pharmacol Sci. 2000 Jan-Apr;4(1-2):21-4. [PubMed:11409185]
  2. Sendo T, Itoh Y, Aki K, Oka M, Oishi R: Carbazochrome sodium sulfonate (AC-17) reverses endothelial barrier dysfunction through inhibition of phosphatidylinositol hydrolysis in cultured porcine endothelial cells. Naunyn Schmiedebergs Arch Pharmacol. 2003 Sep;368(3):175-80. Epub 2003 Aug 20. [PubMed:12928765]
  3. Sendo T, Goromaru T, Aki K, Sakai N, Itoh Y, Oishi R: Carbazochrome attenuates pulmonary dysfunction induced by a radiographic contrast medium in rats. Eur J Pharmacol. 2002 Aug 23;450(2):203-8. [PubMed:12206859]
  4. Basile M, Gidaro S, Pacella M, Biffignandi PM, Gidaro GS: Parenteral troxerutin and carbazochrome combination in the treatment of post-hemorrhoidectomy status: a randomized, double-blind, placebo-controlled, phase IV study. Curr Med Res Opin. 2001;17(4):256-61. [PubMed:11922398]
  5. Ghareeb H, Karaman R. (2015). 6. In Commonly Used Drugs: Uses, Side Effects, Bioavailability and Approaches to Improve It (1st ed., pp. 210). Nova Science Pub Inc; UK ed. edition. [ISBN:9781634638289 ]
External Links
KEGG Drug
D01864
PubChem Compound
5360410
PubChem Substance
310264970
ChemSpider
4514501
ChEMBL
CHEMBL2051960
Drugs.com
Drugs.com Drug Page
Wikipedia
Carbazochrome
ATC Codes
B02BX02 — Carbazochrome
MSDS
Download (47.4 KB)

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility2.91 mg/mLALOGPS
logP-0.47ALOGPS
logP-1.2ChemAxon
logS-1.9ALOGPS
pKa (Strongest Acidic)11.64ChemAxon
pKa (Strongest Basic)1.98ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area108.02 Å2ChemAxon
Rotatable Bond Count1ChemAxon
Refractivity62.16 m3·mol-1ChemAxon
Polarizability23.09 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
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 indoles and derivatives. These are organic compounds containing an indole, which is a bicyclic ring system made up of a six-membered benzene ring fused to a five-membered nitrogen-containing pyrrole ring.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Indoles and derivatives
Sub Class
Not Available
Direct Parent
Indoles and derivatives
Alternative Parents
Semicarbazones / N-alkylpyrrolidines / Vinylogous amides / Trialkylamines / Secondary alcohols / Organic carbonic acids and derivatives / Cyclic ketones / Enamines / Azacyclic compounds / Organopnictogen compounds
show 2 more
Substituents
Indole or derivatives / Semicarbazone / N-alkylpyrrolidine / Pyrrolidine / Semicarbazide / Vinylogous amide / Cyclic ketone / Tertiary aliphatic amine / Tertiary amine / Ketone
show 15 more
Molecular Framework
Aliphatic heteropolycyclic compounds
External Descriptors
Not Available

Drug created on June 20, 2014 15:49 / Updated on November 02, 2018 06:57