Record Information
Version1.0
Creation Date2009-07-21 20:28:25 UTC
Update Date2016-11-09 01:08:45 UTC
Accession NumberCHEM002352
Identification
Common NameAmbenonium
ClassSmall Molecule
DescriptionAmbenonium is only found in individuals that have used or taken this drug. It is a cholinesterase inhibitor used in the management of myasthenia gravis. [Wikipedia] Ambenonium exerts its actions against myasthenia gravis by competitive, reversible inhibition of acetylcholinesterase. The disease myasthenia gravis occurs when the body inappropriately produces antibodies against acetylcholine receptors, and thus inhibits proper acetylcholine signal transmission (when acetylcholine binds to acetylcholine receptors of striated muscle fibers, it stimulates those fibers to contract). Ambenonium reversibly binds acetylcholinesterase at the anionic site, which results in the blockage of the site of acetycholine binding, thereby inhibiting acetylcholine hydrolysis and enhancing cholinergic function through the accumulation of acetycholine at cholinergic synpases. In turn this facilitates transmission of impulses across the myoneural junction and effectively treats the disease.
Contaminant Sources
  • HMDB Contaminants - Urine
  • T3DB toxins
Contaminant Type
  • Amide
  • Amine
  • Anti-Arrhythmia Agent
  • Antimyasthenic Agent
  • Drug
  • Metabolite
  • Organic Compound
  • Organochloride
  • Synthetic Compound
Chemical Structure
Thumb
Synonyms
ValueSource
Ambenonium baseChEBI
AmbenonumChEBI
MytelaseHMDB
Ambenonium chlorideHMDB
Chloride, ambenoniumHMDB
Sanofi winthrop brand OF ambenonium chlorideHMDB
Chemical FormulaC28H42Cl2N4O2
Average Molecular Mass537.565 g/mol
Monoisotopic Mass536.268 g/mol
CAS Registry Number7648-98-8
IUPAC Name[(2-chlorophenyl)methyl](2-{[(2-{[(2-chlorophenyl)methyl]diethylazaniumyl}ethyl)carbamoyl]formamido}ethyl)diethylazanium
Traditional Nameambenonium
SMILESCC[N+](CC)(CCNC(=O)C(=O)NCC[N+](CC)(CC)CC1=CC=CC=C1Cl)CC1=CC=CC=C1Cl
InChI IdentifierInChI=1S/C28H40Cl2N4O2/c1-5-33(6-2,21-23-13-9-11-15-25(23)29)19-17-31-27(35)28(36)32-18-20-34(7-3,8-4)22-24-14-10-12-16-26(24)30/h9-16H,5-8,17-22H2,1-4H3/p+2
InChI KeyOMHBPUNFVFNHJK-UHFFFAOYSA-P
Chemical Taxonomy
Description belongs to the class of organic compounds known as alpha amino acid amides. These are amide derivatives of alpha amino acids.
KingdomOrganic compounds
Super ClassOrganic acids and derivatives
ClassCarboxylic acids and derivatives
Sub ClassAmino acids, peptides, and analogues
Direct ParentAlpha amino acid amides
Alternative Parents
Substituents
  • Alpha-amino acid amide
  • Benzylamine
  • Phenylmethylamine
  • Aralkylamine
  • Chlorobenzene
  • Halobenzene
  • Aryl chloride
  • Aryl halide
  • Monocyclic benzene moiety
  • Benzenoid
  • Tetraalkylammonium salt
  • Quaternary ammonium salt
  • Carboxamide group
  • Secondary carboxylic acid amide
  • Organic nitrogen compound
  • Amine
  • Organonitrogen compound
  • Organochloride
  • Organohalogen compound
  • Organooxygen compound
  • Organic salt
  • Carbonyl group
  • Hydrocarbon derivative
  • Organic oxide
  • Organopnictogen compound
  • Organic oxygen compound
  • Organic cation
  • Aromatic homomonocyclic compound
Molecular FrameworkAromatic homomonocyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
ApplicationsNot Available
Biological Roles
Chemical Roles
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point196-199°C
Boiling PointNot Available
SolubilitySoluble
Predicted Properties
PropertyValueSource
Water Solubility9.4e-07 g/LALOGPS
logP2.27ALOGPS
logP-3.6ChemAxon
logS-8.8ALOGPS
pKa (Strongest Acidic)10.78ChemAxon
pKa (Strongest Basic)-3.6ChemAxon
Physiological Charge2ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area58.2 ŲChemAxon
Rotatable Bond Count15ChemAxon
Refractivity173.57 m³·mol⁻¹ChemAxon
Polarizability59.98 ųChemAxon
Number of Rings2ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyView
1D NMR1H NMR SpectrumNot AvailableSpectrum
1D NMR13C NMR SpectrumNot AvailableSpectrum
1D NMR1H NMR SpectrumNot AvailableSpectrum
1D NMR13C NMR SpectrumNot AvailableSpectrum
1D NMR1H NMR SpectrumNot AvailableSpectrum
1D NMR13C NMR SpectrumNot AvailableSpectrum
1D NMR1H NMR SpectrumNot AvailableSpectrum
1D NMR13C NMR SpectrumNot AvailableSpectrum
1D NMR1H NMR SpectrumNot AvailableSpectrum
1D NMR13C NMR SpectrumNot AvailableSpectrum
1D NMR1H NMR SpectrumNot AvailableSpectrum
1D NMR13C NMR SpectrumNot AvailableSpectrum
1D NMR1H NMR SpectrumNot AvailableSpectrum
1D NMR13C NMR SpectrumNot AvailableSpectrum
1D NMR1H NMR SpectrumNot AvailableSpectrum
1D NMR13C NMR SpectrumNot AvailableSpectrum
1D NMR1H NMR SpectrumNot AvailableSpectrum
1D NMR13C NMR SpectrumNot AvailableSpectrum
1D NMR1H NMR SpectrumNot AvailableSpectrum
1D NMR13C NMR SpectrumNot AvailableSpectrum
Toxicity Profile
Route of ExposureOral - poorly absorbed from the gastrointestinal tract.
Mechanism of ToxicityAmbenonium is a cholinesterase or acetylcholinesterase (AChE) inhibitor. A cholinesterase inhibitor (or 'anticholinesterase') suppresses the action of acetylcholinesterase. Because of its essential function, chemicals that interfere with the action of acetylcholinesterase are potent neurotoxins, causing excessive salivation and eye-watering in low doses, followed by muscle spasms and ultimately death. Nerve gases and many substances used in insecticides have been shown to act by binding a serine in the active site of acetylcholine esterase, inhibiting the enzyme completely. Acetylcholine esterase breaks down the neurotransmitter acetylcholine, which is released at nerve and muscle junctions, in order to allow the muscle or organ to relax. The result of acetylcholine esterase inhibition is that acetylcholine builds up and continues to act so that any nerve impulses are continually transmitted and muscle contractions do not stop. Among the most common acetylcholinesterase inhibitors are phosphorus-based compounds, which are designed to bind to the active site of the enzyme. The structural requirements are a phosphorus atom bearing two lipophilic groups, a leaving group (such as a halide or thiocyanate), and a terminal oxygen.
MetabolismPlasma and hepatic
Toxicity ValuesLD50=150±44 mg/kg (orally in mice).
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesAmbenonium is used to treat muscle weakness due to muscle disease (myasthenia gravis).
Minimum Risk LevelNot Available
Health EffectsAcute exposure to cholinesterase inhibitors can cause a cholinergic crisis characterized by severe nausea/vomiting, salivation, sweating, bradycardia, hypotension, collapse, and convulsions. Increasing muscle weakness is a possibility and may result in death if respiratory muscles are involved. Accumulation of ACh at motor nerves causes overstimulation of nicotinic expression at the neuromuscular junction. When this occurs symptoms such as muscle weakness, fatigue, muscle cramps, fasciculation, and paralysis can be seen. When there is an accumulation of ACh at autonomic ganglia this causes overstimulation of nicotinic expression in the sympathetic system. Symptoms associated with this are hypertension, and hypoglycemia. Overstimulation of nicotinic acetylcholine receptors in the central nervous system, due to accumulation of ACh, results in anxiety, headache, convulsions, ataxia, depression of respiration and circulation, tremor, general weakness, and potentially coma. When there is expression of muscarinic overstimulation due to excess acetylcholine at muscarinic acetylcholine receptors symptoms of visual disturbances, tightness in chest, wheezing due to bronchoconstriction, increased bronchial secretions, increased salivation, lacrimation, sweating, peristalsis, and urination can occur. Certain reproductive effects in fertility, growth, and development for males and females have been linked specifically to organophosphate pesticide exposure. Most of the research on reproductive effects has been conducted on farmers working with pesticides and insecticdes in rural areas. In females menstrual cycle disturbances, longer pregnancies, spontaneous abortions, stillbirths, and some developmental effects in offspring have been linked to organophosphate pesticide exposure. Prenatal exposure has been linked to impaired fetal growth and development. Neurotoxic effects have also been linked to poisoning with OP pesticides causing four neurotoxic effects in humans: cholinergic syndrome, intermediate syndrome, organophosphate-induced delayed polyneuropathy (OPIDP), and chronic organophosphate-induced neuropsychiatric disorder (COPIND). These syndromes result after acute and chronic exposure to OP pesticides.
SymptomsSymptoms of overdose include muscle twitching, weakness and paralysis of voluntary muscles including the tongue, shoulders, neck and arms, blood pressure increase (with or without a slowing of heart rate), a sensation of internal trembling, severe anxiety, and panic. Death may occur rapidly if untreated.
TreatmentIf the compound has been ingested, rapid gastric lavage should be performed using 5% sodium bicarbonate. For skin contact, the skin should be washed with soap and water. If the compound has entered the eyes, they should be washed with large quantities of isotonic saline or water. In serious cases, atropine and/or pralidoxime should be administered. Anti-cholinergic drugs work to counteract the effects of excess acetylcholine and reactivate AChE. Atropine can be used as an antidote in conjunction with pralidoxime or other pyridinium oximes (such as trimedoxime or obidoxime), though the use of '-oximes' has been found to be of no benefit, or possibly harmful, in at least two meta-analyses. Atropine is a muscarinic antagonist, and thus blocks the action of acetylcholine peripherally.
Concentrations
Not Available
DrugBank IDDB01122
HMDB IDHMDB0015254
FooDB IDNot Available
Phenol Explorer IDNot Available
KNApSAcK IDNot Available
BiGG IDNot Available
BioCyc IDNot Available
METLIN IDNot Available
PDB IDNot Available
Wikipedia LinkAmbenonium
Chemspider ID2046
ChEBI ID2627
PubChem Compound ID2131
Kegg Compound IDC07773
YMDB IDNot Available
ECMDB IDNot Available
References
Synthesis Reference

Kirchner, F.K.; U.S. Patent 3,096,373; July 2,1963; assigned to Sterling Drug Inc.

MSDSLink
General ReferencesNot Available