Identification

Name
Edrophonium
Accession Number
DB01010  (APRD00944)
Type
Small Molecule
Groups
Approved
Description

A rapid-onset, short-acting cholinesterase inhibitor used in cardiac arrhythmias and in the diagnosis of myasthenia gravis. It has also been used as an antidote to curare principles.

Structure
Thumb
Synonyms
  • (3-hydroxyphenyl)dimethylethylammonium
  • 3-hydroxy-N,N-dimethyl-N-ethylanilinium
  • Edrophonium cation
  • Edrophonium ion
  • Ethyl-(3-hydroxy-phenyl)-dimethyl-ammonium
  • N-ethyl-3-hydroxy-N,N-dimethylanilinium
  • N-ethyl-3-hydroxy-N,N-dimethylbenzenaminium
Product Ingredients
IngredientUNIICASInChI Key
Edrophonium bromideKX008093VW302-83-0CAEPIUXAUPYIIJ-UHFFFAOYSA-N
Edrophonium chlorideQO611KSM5P116-38-1BXKDSDJJOVIHMX-UHFFFAOYSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
EnlonInjection10 mg/1mLIntramuscular; IntravenousBaxter Laboratories2006-10-17Not applicableUs
Enlon 10mg/mlLiquid10 mgIntravenousBaxter Laboratories1996-09-182008-01-28Canada
Enlon Liq IV 10mg/mlLiquid10 mgIntravenousOhmeda Pharmaceutical Products, Division Of Boc Canada Limited1995-12-311996-09-26Canada
TensilonLiquid10 mgIntramuscular; IntravenousValeant Canada Lp Valeant Canada S.E.C.1988-12-312016-07-08Canada
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
EnlonInjection, solution10 mg/1mLIntramuscular; IntravenousMylan Institutional2013-04-222018-09-19Us
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Enlon PlusEdrophonium chloride (10 mg/1mL) + Atropine sulfate (0.14 mg/1mL)Injection, solutionIntravenousBioniche Pharma USA LLC2008-10-012009-11-25Us
Enlon PlusEdrophonium chloride (10 mg/1mL) + Atropine sulfate (0.14 mg/1mL)Injection, solutionIntravenousMylan Institutional1991-11-062017-12-31Us
Enlon-PlusEdrophonium chloride (10 mg/1mL) + Atropine sulfate (0.14 mg/1.0mL)InjectionIntravenousBaxter Laboratories2006-03-09Not applicableUs
Enlon-PlusEdrophonium chloride (10.0 mg/1.0mL) + Atropine sulfate (0.14 mg/1.0mL)InjectionIntravenousBaxter Laboratories2006-03-09Not applicableUs
International/Other Brands
Antirex (Kyorin) / Reversol
Categories
UNII
70FP3JLY7N
CAS number
312-48-1
Weight
Average: 166.2401
Monoisotopic: 166.123189139
Chemical Formula
C10H16NO
InChI Key
VWLHWLSRQJQWRG-UHFFFAOYSA-O
InChI
InChI=1S/C10H15NO/c1-4-11(2,3)9-6-5-7-10(12)8-9/h5-8H,4H2,1-3H3/p+1
IUPAC Name
N-ethyl-3-hydroxy-N,N-dimethylanilinium
SMILES
CC[N+](C)(C)C1=CC(O)=CC=C1

Pharmacology

Indication

For the differential diagnosis of myasthenia gravis and as an adjunct in the evaluation of treatment requirements in this disease. It may also be used for evaluating emergency treatment in myasthenic crises.

Associated Conditions
Pharmacodynamics

Edrophonium is a short and rapid-acting anticholinesterase drug. Its effect is manifest within 30 to 60 seconds after injection and lasts an average of 10 minutes. Edrophonium's pharmacologic action is due primarily to the inhibition or inactivation of acetylcholinesterase at sites of cholinergic transmission. Nicotinic acetylcholine (nAChR)receptors are found throughout the body, especially on muscle. Stimulation of these receptors causes to muscle contraction. In myasthenia gravis the body's immune system destroys many of the nicotinic acetylcholine receptors, so that the muscle becomes less responsive to nervous stimulation. Edrophonium chloride increases the amount of acetylcholine at the nerve endings. Increased levels of acetylcholine allow the remaining receptors to function more efficiently.

Mechanism of action

Edrophonium works by prolonging the action acetylcholine, which is found naturally in the body. It does this by inhibiting the action of the enzyme acetylcholinesterase. Acetylcholine stimulates nicotinic and muscarinic receptors. When stimulated, these receptors have a range of effects.

TargetActionsOrganism
AAcetylcholinesterase
inhibitor
Human
ACholinesterase
inhibitor
Human
Absorption

Rapidly absorbed.

Volume of distribution
  • 1.6±0.4 L/kg [Adults]
  • 2.2±1.5 L/kg [Children (0.08-10 yrs)]
  • 1.8±1.2 L/kg [Elderly (65-75 yrs)]
Protein binding
Not Available
Metabolism
Not Available
Route of elimination

Edrophonium is primarily renally excreted with 67% of the dose appearing in the urine. Hepatic metabolism and biliary excretion have also been demonstrated in animals

Half life

Distribution half-life is 7 to 12 minutes. Elimination half-life is 33 to 110 minutes.

Clearance
  • 6.8 +/- 2. mL/kg/min [Adults]
  • 6.4 +/- 3.9 mL/kg/min [Children (0.08-10 yrs)]
  • 2.9 +/- 1.9 mL/kg/min [Elderly (65-75 yrs)]
Toxicity

With drugs of this type, muscarine-like symptoms (nausea, vomiting, diarrhea, sweating, increased bronchial and salivary secretions and bradycardia) often appear with overdosage (cholinergic crisis).

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

Interactions

Drug Interactions
DrugInteraction
AbacavirEdrophonium may decrease the excretion rate of Abacavir which could result in a higher serum level.
AcarboseAcarbose may decrease the excretion rate of Edrophonium which could result in a higher serum level.
AcebutololEdrophonium may increase the bradycardic activities of Acebutolol.
AceclofenacAceclofenac may decrease the excretion rate of Edrophonium which could result in a higher serum level.
AcemetacinAcemetacin may decrease the excretion rate of Edrophonium which could result in a higher serum level.
AcetaminophenAcetaminophen may decrease the excretion rate of Edrophonium which could result in a higher serum level.
AcetylcholineThe risk or severity of adverse effects can be increased when Edrophonium is combined with Acetylcholine.
AcetyldigitoxinEdrophonium may increase the atrioventricular blocking (AV block) and arrhythmogenic activities of Acetyldigitoxin.
AcetyldigoxinEdrophonium may increase the atrioventricular blocking (AV block) and arrhythmogenic activities of Acetyldigoxin.
Acetylsalicylic acidAcetylsalicylic acid may decrease the excretion rate of Edrophonium which could result in a higher serum level.
Food Interactions
Not Available

References

Synthesis Reference

Terrell, R.C.; U.S. Patents 3,469,011; September 23, 1969 and 3,527,813; September 8, 1970; both assigned to Air Reduction Company, Incorporated.

General References
Not Available
External Links
Human Metabolome Database
HMDB0015145
KEGG Compound
C06976
PubChem Compound
3202
PubChem Substance
46507530
ChemSpider
3090
BindingDB
120262
ChEBI
251408
ChEMBL
CHEMBL1104
Therapeutic Targets Database
DAP000562
PharmGKB
PA449437
HET
EDR
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Edrophonium
PDB Entries
1ax9 / 2ack
MSDS
Download (50.8 KB)

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
  • Hospira inc
  • Watson laboratories inc
  • Bioniche pharma usa llc
  • Organon usa inc
  • Valeant pharmaceuticals international
Packagers
  • Akorn Inc.
  • Baxter International Inc.
  • Bioniche Pharma
  • Taylor Pharmaceuticals
  • Valeant Ltd.
Dosage forms
FormRouteStrength
InjectionIntramuscular; Intravenous10 mg/1mL
Injection, solutionIntramuscular; Intravenous10 mg/1mL
LiquidIntravenous10 mg
Injection, solutionIntravenous
InjectionIntravenous
LiquidIntramuscular; Intravenous10 mg
Prices
Unit descriptionCostUnit
Enlon-plus multi-dose vial1.92USD ml
Enlon-plus ampul1.87USD ml
Enlon 10 mg/ml vial0.69USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Liquid
Experimental Properties
PropertyValueSource
melting point (°C)162-163Terrell, R.C.; U.S. Patents 3,469,011; September 23, 1969 and 3,527,813; September 8, 1970; both assigned to Air Reduction Company, Incorporated.
water solubilityAppreciable as liquid hydrochloride saltNot Available
logP-2.95Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0486 mg/mLALOGPS
logP-1.6ALOGPS
logP-1.9ChemAxon
logS-3.6ALOGPS
pKa (Strongest Acidic)8.59ChemAxon
pKa (Strongest Basic)-6.1ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count1ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area20.23 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity62.41 m3·mol-1ChemAxon
Polarizability19.15 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption-0.8406
Blood Brain Barrier+0.8867
Caco-2 permeable+0.6827
P-glycoprotein substrateNon-substrate0.6628
P-glycoprotein inhibitor INon-inhibitor0.9814
P-glycoprotein inhibitor IINon-inhibitor0.9163
Renal organic cation transporterNon-inhibitor0.8132
CYP450 2C9 substrateNon-substrate0.7682
CYP450 2D6 substrateNon-substrate0.6247
CYP450 3A4 substrateSubstrate0.569
CYP450 1A2 substrateNon-inhibitor0.9045
CYP450 2C9 inhibitorNon-inhibitor0.9181
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorNon-inhibitor0.918
CYP450 3A4 inhibitorNon-inhibitor0.9523
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9202
Ames testAMES toxic0.6723
CarcinogenicityCarcinogens 0.5357
BiodegradationNot ready biodegradable0.903
Rat acute toxicity2.4293 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8461
hERG inhibition (predictor II)Non-inhibitor0.6585
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

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

Taxonomy

Description
This compound belongs to the class of organic compounds known as aniline and substituted anilines. These are organic compounds containing an aminobenzene moiety.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Aniline and substituted anilines
Direct Parent
Aniline and substituted anilines
Alternative Parents
m-Aminophenols / 1-hydroxy-4-unsubstituted benzenoids / 1-hydroxy-2-unsubstituted benzenoids / Quaternary ammonium salts / Organopnictogen compounds / Organooxygen compounds / Organic salts / Hydrocarbon derivatives / Amines / Organic cations
Substituents
Aminophenol / M-aminophenol / Aniline or substituted anilines / 1-hydroxy-4-unsubstituted benzenoid / 1-hydroxy-2-unsubstituted benzenoid / Phenol / Quaternary ammonium salt / Amine / Organic nitrogen compound / Hydrocarbon derivative
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
phenols, quaternary ammonium ion (CHEBI:251408)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Serine hydrolase activity
Specific Function
Terminates signal transduction at the neuromuscular junction by rapid hydrolysis of the acetylcholine released into the synaptic cleft. Role in neuronal apoptosis.
Gene Name
ACHE
Uniprot ID
P22303
Uniprot Name
Acetylcholinesterase
Molecular Weight
67795.525 Da
References
  1. Ravelli RB, Raves ML, Ren Z, Bourgeois D, Roth M, Kroon J, Silman I, Sussman JL: Static Laue diffraction studies on acetylcholinesterase. Acta Crystallogr D Biol Crystallogr. 1998 Nov 1;54(Pt 6 Pt 2):1359-66. [PubMed:10089512]
  2. Keymer JE, Gaete J, Kameid G, Alvarez J: Acetylcholinesterase and inhibitors: effects upon normal and regenerating nerves of the rat. Eur J Neurosci. 1999 Mar;11(3):1049-57. [PubMed:10103097]
  3. Huby F, Mallet S, Hoste H: Role of acetylcholinesterase (AChE) secreted by parasitic nematodes on the growth of the cell line from epithelial origin HT29-D4. Parasitology. 1999 May;118 ( Pt 5):489-98. [PubMed:10363282]
  4. Luo C, Saxena A, Ashani Y, Leader H, Radic Z, Taylor P, Doctor BP: Role of edrophonium in prevention of the re-inhibition of acetylcholinesterase by phosphorylated oxime. Chem Biol Interact. 1999 May 14;119-120:129-35. [PubMed:10421446]
  5. Luo C, Saxena A, Smith M, Garcia G, Radic Z, Taylor P, Doctor BP: Phosphoryl oxime inhibition of acetylcholinesterase during oxime reactivation is prevented by edrophonium. Biochemistry. 1999 Aug 3;38(31):9937-47. [PubMed:10433700]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
  7. Martin-Biosca Y, Asensi-Bernardi L, Villanueva-Camanas RM, Sagrado S, Medina-Hernandez MJ: Screening of acetylcholinesterase inhibitors by CE after enzymatic reaction at capillary inlet. J Sep Sci. 2009 May;32(10):1748-56. doi: 10.1002/jssc.200800701. [PubMed:19472276]
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. Harel M, Sussman JL, Krejci E, Bon S, Chanal P, Massoulie J, Silman I: Conversion of acetylcholinesterase to butyrylcholinesterase: modeling and mutagenesis. Proc Natl Acad Sci U S A. 1992 Nov 15;89(22):10827-31. [PubMed:1438284]
  2. Saxena A, Redman AM, Jiang X, Lockridge O, Doctor BP: Differences in active site gorge dimensions of cholinesterases revealed by binding of inhibitors to human butyrylcholinesterase. Biochemistry. 1997 Dec 2;36(48):14642-51. [PubMed:9398183]

Drug created on June 13, 2005 07:24 / Updated on November 02, 2018 09:16