Ambenonium

Common Name

Ambenonium Description

Ambenonium 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 stimliates those fibers to contract). Ambenonium reversibly binds acetylcholinesterase at the anionic site, which reslits in the blockage of the site of acetycholine binding, thereby inhibiting acetylcholine hydrolysis and enhancing cholinergic function through the accumliation of acetycholine at cholinergic synpases. In turn this facilitates transmission of implises across the myoneural junction and effectively treats the disease. Structure

Synonyms

Value Source Ambenonium baseChEBI AmbenonumChEBI MytelaseMeSH Ambenonium chlorideMeSH Chloride, ambenoniumMeSH Sanofi winthrop brand OF ambenonium chlorideMeSH

Chemical Formlia

C28H42Cl2N4O2 Average Molecliar Weight

537.565 Monoisotopic Molecliar Weight

536.268482022 IUPAC Name

[(2-chlorophenyl)methyl](2-{[(2-{[(2-chlorophenyl)methyl]diethylazaniumyl}ethyl)carbamoyl]formamido}ethyl)diethylazanium Traditional Name

ambenonium CAS Registry Number

7648-98-8 SMILES

CC[N+](CC)(CCNC(=O)C(=O)NCC[N+](CC)(CC)CC1=CC=CC=C1Cl)CC1=CC=CC=C1Cl

InChI Identifier

InChI=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 Key

OMHBPUNFVFNHJK-UHFFFAOYSA-P Chemical Taxonomy Description

This compound belongs to the class of chemical entities known as alpha amino acid amides. These are amide derivatives of alpha amino acids. Kingdom

Chemical entities Super Class

Organic compounds Class

Organic acids and derivatives Sub Class

Carboxylic acids and derivatives Direct Parent

Alpha amino acid amides Alternative Parents

  • Phenylmethylamines
  • Benzylamines
  • Chlorobenzenes
  • Aralkylamines
  • Aryl chlorides
  • Tetraalkylammonium salts
  • Secondary carboxylic acid amides
  • Organopnictogen compounds
  • Organochlorides
  • Organic salts
  • Organic oxides
  • Hydrocarbon derivatives
  • Carbonyl compounds
  • Organic cations
  • 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
  • Molecliar Framework

    Aromatic homomonocyclic compounds External Descriptors

  • quaternary ammonium ion (CHEBI:2627 )
  • Ontology Status

    Expected but not Quantified Origin

  • Drug
  • Biofunction

  • Antiarrhythmic Agents
  • Antimyasthenics
  • Application

  • Pharmaceutical
  • Cellliar locations

  • Cytoplasm
  • Physical Properties State

    Solid Experimental Properties

    Property Value Reference Melting Point196 – 199 °CNot Available Boiling PointNot AvailableNot Available Water Solubility9.42e-07 g/LNot Available LogPNot AvailableNot Available

    Predicted Properties

    Property Value Source Water Solubility9.42e-07 mg/mLALOGPS 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 Å2ChemAxon Rotatable Bond Count15ChemAxon Refractivity173.57 m3·mol-1ChemAxon Polarizability59.98 Å3ChemAxon Number of Rings2ChemAxon Bioavailability0ChemAxon Rlie of FiveYesChemAxon Ghose FilterYesChemAxon Vebers RlieYesChemAxon MDDR-like RlieYesChemAxon

    Spectra Spectra

    Not Available Biological Properties Cellliar Locations

  • Cytoplasm
  • Biofluid Locations

  • Blood
  • Urine
  • Tissue Location

    Not Available Pathways

    Not Available Normal Concentrations

    Biofluid Status Value Age Sex Condition Reference Details BloodExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB01122

  • 21059682
  • details UrineExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB01122

  • 21059682
  • details

    Abnormal Concentrations

    Not Available Predicted Concentrations

    Biofluid Value Original age Original sex Original condition Comments Blood0-2 uMAdlit (>18 years old)BothNormalPredicted based on drug qualities Blood0-1 umol/mmol creatinineAdlit (>18 years old)BothNormalPredicted based on drug qualities

    Associated Disorders and Diseases Disease References

    None Associated OMIM IDs

    None External Links DrugBank ID

    DB01122 DrugBank Metabolite ID

    Not Available Phenol Explorer Compound ID

    Not Available Phenol Explorer Metabolite ID

    Not Available FoodDB ID

    Not Available KNApSAcK ID

    Not Available Chemspider ID

    2046 KEGG Compound ID

    C07773 BioCyc ID

    Not Available BiGG ID

    Not Available Wikipedia Link

    Ambenonium NuGOwiki Link

    HMDB15254 Metagene Link

    HMDB15254 METLIN ID

    Not Available PubChem Compound

    2131 PDB ID

    Not Available ChEBI ID

    2627

    Product: 7-FAM SE

    References Synthesis Reference Not Available Material Safety Data Sheet (MSDS) Not Available General References Not Available

    Enzymes

    General function:
    Involved in carboxylesterase 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
    Molecular weight:
    67795.525
    References
    1. Lockhart B, Closier M, Howard K, Steward C, Lestage P: Differential inhibition of [3H]-oxotremorine-M and [3H]-quinuclinidyl benzilate binding to muscarinic receptors in rat brain membranes with acetylcholinesterase inhibitors. Naunyn Schmiedebergs Arch Pharmacol. 2001 Apr;363(4):429-38. [PubMed:11330337 ]
    2. Hodge AS, Humphrey DR, Rosenberry TL: Ambenonium is a rapidly reversible noncovalent inhibitor of acetylcholinesterase, with one of the highest known affinities. Mol Pharmacol. 1992 May;41(5):937-42. [PubMed:1588924 ]
    3. Papp MI, Komoly S, Szirmai IG, Kovacs T: Similarities between CSF-brain extracellular transfer and neurofibrillary tangle invasion in Alzheimers disease. Neurobiol Aging. 2006 Mar;27(3):402-12. Epub 2005 Jun 27. [PubMed:15982786 ]
    4. Kenakin TP, Beek D: Self-cancellation of drug properties as a mode of organ selectivity: the antimuscarinic effects of ambenonium. J Pharmacol Exp Ther. 1985 Mar;232(3):732-40. [PubMed:2857786 ]
    5. Webb GD: Affinity of benzoquinonium and ambenonium derivatives for the acetylcholine receptor, tested on the electroplax, and for acetylcholinesterase in solution. Biochim Biophys Acta. 1965 May 25;102(1):172-84. [PubMed:5833399 ]
    6. Bolognesi ML, Cavalli A, Andrisano V, Bartolini M, Banzi R, Antonello A, Rosini M, Melchiorre C: Design, synthesis and biological evaluation of ambenonium derivatives as AChE inhibitors. Farmaco. 2003 Sep;58(9):917-28. [PubMed:13679187 ]
    7. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
    General function:
    Involved in carboxylesterase activity
    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
    Molecular weight:
    68417.575
    References
    1. Yamamoto K, Kohda Y, Sawada Y, Iga T: Pharmacokinetics of ambenonium, a reversible cholinesterase inhibitor, in rats. Biopharm Drug Dispos. 1991 Nov;12(8):613-25. [PubMed:1801966 ]

    PMID: 8182710