Identification
- Summary
Ambenonium is a cholinesterase inhibitor that targets both muscarinic and nicotinic receptors indicated for the treatment of myasthenia gravis.
- Generic Name
- Ambenonium
- DrugBank Accession Number
- DB01122
- Background
Ambenonium is a cholinesterase inhibitor. It is used in the management of myasthenia gravis.
- Type
- Small Molecule
- Groups
- Approved
- Structure
Structure for Ambenonium (DB01122)
- Weight
- Average: 537.565
Monoisotopic: 536.268482022 - Chemical Formula
- C28H42Cl2N4O2
- Synonyms
- Ambenonium
- Ambenonium base
- Ambenonum
Pharmacology
- Indication
Ambenonium is used to treat muscle weakness due to muscle disease (myasthenia gravis).
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Contraindications & Blackbox Warnings
Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API- Pharmacodynamics
Ambenonium, similar to pyridostigmine and neostigmine, is used for the treatment of muscle weakness and fatigue in people with myasthenia gravis. It is postulated to exert its therapeutic effect by enhancing cholinergic function through the inhibition of the acetylcholine hydrolysis by acetylcholinesterase. Increased levels of acetylcholine has peripheral effects, as acetylcholine is also used in the brain, where it tends to cause excitatory actions. The glands that receive impulses from the parasympathetic part of the autonomic nervous system are also stimulated in the same way. This is why an increase in acetylcholine causes a decreased heart rate and increased production of saliva. Ambenonium is used less commonly than neostigmine or pyridostigmine but may be preferred in patients hypersensitive to the bromide ion. Ambenonium produces fewer muscarinic side effects than neostigmine, but more than pyridostigmine.
- Mechanism of action
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. Elevated acetylcholine levels lead to facilitates transmission of impulses across the myoneural junction.
Target Actions Organism AAcetylcholinesterase inhibitorHumans - Absorption
Oral - poorly absorbed from the gastrointestinal tract.
- Volume of distribution
Not Available
- Protein binding
Not Available
- Metabolism
Plasma and hepatic
- Route of elimination
Not Available
- Half-life
Not Available
- Clearance
Not Available
- Adverse Effects
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.- Toxicity
LD50=150±44 mg/kg (orally in mice). Symptoms 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.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAcebutolol Ambenonium may increase the bradycardic activities of Acebutolol. Acetylcholine The risk or severity of adverse effects can be increased when Ambenonium is combined with Acetylcholine. Aclidinium Ambenonium may increase the neuromuscular blocking activities of Aclidinium. Amantadine The therapeutic efficacy of Amantadine can be decreased when used in combination with Ambenonium. Amifampridine The risk or severity of adverse effects can be increased when Ambenonium is combined with Amifampridine. - Food Interactions
- Not Available
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Product Ingredients
Ingredient UNII CAS InChI Key Ambenonium chloride 51FOB87G3I 115-79-7 DXUUXWKFVDVHIK-UHFFFAOYSA-N - International/Other Brands
- Mysuran
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Mytelase Tablet 10 mg/1 Oral Sanofi Aventis 1971-09-08 2013-03-31 US 
Categories
- ATC Codes
- N07AA30 — Ambenonium
- Drug Categories
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as alpha amino acid amides. These are amide derivatives of alpha amino acids.
- Kingdom
- Organic compounds
- Super Class
- Organic acids and derivatives
- Class
- Carboxylic acids and derivatives
- Sub Class
- Amino acids, peptides, and analogues
- 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 show 4 more
- Substituents
- Alpha-amino acid amide / Amine / Aralkylamine / Aromatic homomonocyclic compound / Aryl chloride / Aryl halide / Benzenoid / Benzylamine / Carbonyl group / Carboxamide group show 18 more
- Molecular Framework
- Aromatic homomonocyclic compounds
- External Descriptors
- quaternary ammonium ion (CHEBI:2627)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- L16PUN799N
- CAS number
- 7648-98-8
- InChI Key
- OMHBPUNFVFNHJK-UHFFFAOYSA-P
- InChI
- 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
- IUPAC Name
- [(2-chlorophenyl)methyl](2-{[(2-{[(2-chlorophenyl)methyl]diethylazaniumyl}ethyl)carbamoyl]formamido}ethyl)diethylazanium
- SMILES
- CC[N+](CC)(CCNC(=O)C(=O)NCC[N+](CC)(CC)CC1=CC=CC=C1Cl)CC1=CC=CC=C1Cl
References
- Synthesis Reference
Kirchner, F.K.; U.S. Patent 3,096,373; July 2,1963; assigned to Sterling Drug Inc.
- General References
- Not Available
- External Links
- Human Metabolome Database
- HMDB0015254
- KEGG Compound
- C07773
- PubChem Compound
- 2131
- PubChem Substance
- 46508143
- ChemSpider
- 2046
- BindingDB
- 50262988
- 623
- ChEBI
- 2627
- ChEMBL
- CHEMBL1652
- ZINC
- ZINC000003995599
- Therapeutic Targets Database
- DAP000893
- PharmGKB
- PA164764601
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Ambenonium_chloride
- MSDS
- Download (166 KB)
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Bayer Healthcare
- Sanofi-Aventis Inc.
- Dosage Forms
Form Route Strength Tablet Oral 10 mg/1 - Prices
Unit description Cost Unit Mytelase 10 mg caplet 1.86USD caplet Mytelase 10 mg tablet 1.86USD tablet DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 196-199 °C Kirchner, F.K.; U.S. Patent 3,096,373; July 2,1963; assigned to Sterling Drug Inc. water solubility Soluble Not Available - Predicted Properties
Property Value Source Water Solubility 9.42e-07 mg/mL ALOGPS logP 2.27 ALOGPS logP -3.6 Chemaxon logS -8.8 ALOGPS pKa (Strongest Acidic) 11.48 Chemaxon pKa (Strongest Basic) -3.6 Chemaxon Physiological Charge 2 Chemaxon Hydrogen Acceptor Count 2 Chemaxon Hydrogen Donor Count 2 Chemaxon Polar Surface Area 58.2 Å2 Chemaxon Rotatable Bond Count 15 Chemaxon Refractivity 173.57 m3·mol-1 Chemaxon Polarizability 59.98 Å3 Chemaxon Number of Rings 2 Chemaxon Bioavailability 0 Chemaxon Rule of Five No Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption - 0.9618 Blood Brain Barrier + 0.8373 Caco-2 permeable + 0.5168 P-glycoprotein substrate Substrate 0.8725 P-glycoprotein inhibitor I Non-inhibitor 0.6717 P-glycoprotein inhibitor II Non-inhibitor 0.766 Renal organic cation transporter Non-inhibitor 0.823 CYP450 2C9 substrate Non-substrate 0.7865 CYP450 2D6 substrate Non-substrate 0.7008 CYP450 3A4 substrate Substrate 0.5842 CYP450 1A2 substrate Non-inhibitor 0.9046 CYP450 2C9 inhibitor Non-inhibitor 0.907 CYP450 2D6 inhibitor Non-inhibitor 0.6899 CYP450 2C19 inhibitor Non-inhibitor 0.9025 CYP450 3A4 inhibitor Non-inhibitor 0.8308 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.538 Ames test Non AMES toxic 0.7312 Carcinogenicity Non-carcinogens 0.6118 Biodegradation Not ready biodegradable 0.9927 Rat acute toxicity 2.4379 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9665 hERG inhibition (predictor II) Inhibitor 0.8507
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Not Available
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 230.8550384 predictedDarkChem Lite v0.1.0 [M-H]- 206.80727 predictedDeepCCS 1.0 (2019) [M+H]+ 229.7746384 predictedDarkChem Lite v0.1.0 [M+H]+ 209.16527 predictedDeepCCS 1.0 (2019) [M+Na]+ 230.4538384 predictedDarkChem Lite v0.1.0 [M+Na]+ 215.58124 predictedDeepCCS 1.0 (2019)
Targets
- Kind
- Protein
- Organism
- Humans
- 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
- 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. [Article]
- 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. [Article]
- Papp MI, Komoly S, Szirmai IG, Kovacs T: Similarities between CSF-brain extracellular transfer and neurofibrillary tangle invasion in Alzheimer's disease. Neurobiol Aging. 2006 Mar;27(3):402-12. Epub 2005 Jun 27. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- 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
- 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. [Article]
Drug created at June 13, 2005 13:24 / Updated at February 02, 2024 22:53