Hexafluronium

Identification

Name
Hexafluronium
Accession Number
DB00941  (APRD01013)
Type
Small Molecule
Groups
Approved
Description

Hexafluronium bromide is a neuromuscular blocking agent used in anesthesiology to prolong and potentiate the skeletal muscle relaxing action of suxamethonium during surgery. It is known to bind and block the activity of plasma cholinesterases.

Structure
Thumb
Synonyms
  • Hexafluorenium
  • Hexafluorenium cation
  • Hexafluorenium ion
  • Hexamethylenebis(fluoren-9-yldimethylammonium)
External IDs
Not Available
Product Ingredients
IngredientUNIICASInChI Key
Hexafluronium bromideB64NJG83K2 317-52-2WDEFPRUEZRUYNW-UHFFFAOYSA-L
Approved Prescription Products
Not Available
Approved Generic Prescription Products
Not Available
Approved Over the Counter Products
Not Available
Unapproved/Other Products
Not Available
International/Other Brands
Mylaxen
Brand mixtures
Not Available
Categories
UNII
55W5L6G81R
CAS number
4844-10-4
Weight
Average: 502.745
Monoisotopic: 502.333702201
Chemical Formula
C36H42N2
InChI Key
HDZAQYPYABGTCL-UHFFFAOYSA-N
InChI
InChI=1S/C36H42N2/c1-37(2,35-31-21-11-7-17-27(31)28-18-8-12-22-32(28)35)25-15-5-6-16-26-38(3,4)36-33-23-13-9-19-29(33)30-20-10-14-24-34(30)36/h7-14,17-24,35-36H,5-6,15-16,25-26H2,1-4H3/q+2
IUPAC Name
N-{6-[(9H-fluoren-9-yl)dimethylazaniumyl]hexyl}-N,N-dimethyl-9H-fluoren-9-aminium
SMILES
C[N+](C)(CCCCCC[N+](C)(C)C1C2=C(C=CC=C2)C2=C1C=CC=C2)C1C2=C(C=CC=C2)C2=C1C=CC=C2

Pharmacology

Indication

Used as an adjunct with succinylcholine (or suxamethonium chloride) to prolong muscle relaxation and to prevent succinylcholine-induced muscle fasciculations.

Structured Indications
Not Available
Pharmacodynamics

Hexafluronium bromide is a cholinesterase antagonist that can be used to prolong the relaxation effects of succinylcholine or suxamethonium chloride. Suxamethonium acts as a depolarizing muscle relaxant. It imitates the action of acetylcholine at the neuromuscular junction and is degraded by pseudocholinesterase, a plasma cholinesterase. The prolonged stimulation of the acetylcholine receptor results first in disorganized muscle contractions, then in profound relaxation. Cholinesterases catalyze the hydrolysis of the neurotransmitter acetylcholine into choline and acetic acid, a reaction necessary to allow a cholinergic neuron to return to its resting state after activation. There are two types of cholinesterase acetylcholinesterase and pseuodocholinesterase. The first hydrolyses acetylcholine more quickly; the latter hydrolyses butyrylcholine and succinylcholine more quickly. An absence or mutation of the pseudocholinesterase enzyme leads to a medical condition known simply as pseudocholinesterase deficiency. This is a silent condition that only manifests itself when people who have the deficiency receive the muscle relaxants succinylcholine or mivacurium during a surgery.

Mechanism of action

Hexafluronium bromide is a non-competitive reversible inhibitor of human plasma cholinesterase or pseudocholinesterase. Hexafluornium probably binds to anionic side receptors near the active center, causing a conformational change in the enzyme, preventing acylation of the esteratic site. The esteratic site on cholistereases is where acetylcholine is hydrolyzed to acetic acid and choline.

TargetActionsOrganism
ACholinesterase
inhibitor
Human
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

LD50 = 280 mg/kg (mouse, oral)

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

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

Synthesis Reference
Not Available
General References
Not Available
External Links
KEGG Drug
D04435
ChemSpider
3475
ChEBI
135804
ChEMBL
CHEMBL1201349
Therapeutic Targets Database
DAP000963
PharmGKB
PA164743020
Wikipedia
Hexafluronium_bromide
ATC Codes
M03AC05 — Hexafluronium
AHFS Codes
Not Available
PDB Entries
Not Available
FDA label
Not Available
MSDS
Not Available

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
  • Medpointe pharmaceuticals medpointe healthcare inc
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)153.5 °CPhysProp
logP-0.06Not Available
Predicted Properties
PropertyValueSource
Water Solubility2.09e-07 mg/mLALOGPS
logP1.83ALOGPS
logP-0.28ChemAxon
logS-9.4ALOGPS
pKa (Strongest Acidic)16.64ChemAxon
Physiological Charge2ChemAxon
Hydrogen Acceptor Count0ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area0 Å2ChemAxon
Rotatable Bond Count9ChemAxon
Refractivity184.49 m3·mol-1ChemAxon
Polarizability60.41 Å3ChemAxon
Number of Rings6ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption-0.9105
Blood Brain Barrier+0.9722
Caco-2 permeable+0.6779
P-glycoprotein substrateSubstrate0.6897
P-glycoprotein inhibitor INon-inhibitor0.7472
P-glycoprotein inhibitor IIInhibitor0.7951
Renal organic cation transporterInhibitor0.6954
CYP450 2C9 substrateNon-substrate0.7536
CYP450 2D6 substrateSubstrate0.5964
CYP450 3A4 substrateSubstrate0.6599
CYP450 1A2 substrateNon-inhibitor0.7169
CYP450 2C9 inhibitorNon-inhibitor0.9223
CYP450 2D6 inhibitorNon-inhibitor0.6863
CYP450 2C19 inhibitorNon-inhibitor0.707
CYP450 3A4 inhibitorNon-inhibitor0.9637
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.85
Ames testNon AMES toxic0.7711
CarcinogenicityNon-carcinogens0.7479
BiodegradationNot ready biodegradable0.9234
Rat acute toxicity2.6334 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8767
hERG inhibition (predictor II)Inhibitor0.8131
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )

Spectra

Mass Spec (NIST)
Not Available
Spectra
Not Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as hexamethonium compounds. These are organic compounds containing a N,N,N,N',N',N'-hexamethylhexane-1,6-diaminium moiety.
Kingdom
Organic compounds
Super Class
Organic nitrogen compounds
Class
Organonitrogen compounds
Sub Class
Quaternary ammonium salts
Direct Parent
Hexamethonium compounds
Alternative Parents
Fluorenes / Aralkylamines / Tetraalkylammonium salts / Hydrocarbon derivatives / Organic cations
Substituents
Hexamethonium / Fluorene / Aralkylamine / Benzenoid / Tetraalkylammonium salt / Hydrocarbon derivative / Amine / Organic cation / Aromatic homopolycyclic compound
Molecular Framework
Aromatic homopolycyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Identical protein binding
Specific Function
Esterase with broad substrate specificity. Contributes to the inactivation of the neurotransmitter acetylcholine. Can degrade neurotoxic organophosphate esters.
Gene Name
BCHE
Uniprot ID
P06276
Uniprot Name
Cholinesterase
Molecular Weight
68417.575 Da
References
  1. Schuh FR: Interaction of hexafluorenium with human plasma cholinesterase in comparison with hexamethonium. Naunyn Schmiedebergs Arch Pharmacol. 1976;293(1):11-3. [PubMed:948350 ]
  2. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
Drug created on June 13, 2005 07:24 / Updated on September 01, 2017 10:34