Details of the Drug

General Information of Drug (ID: DMOP0BL)

• Drug Name: Ambenonium
• Synonyms: Ambenonum; Ambenonium Base; Ambenonium kation; Mytelase (TN); (2-chlorophenyl)methyl-[2-[[2-[2-[(2-chlorophenyl)methyl-diethylazaniumyl]ethylamino]-2-oxoacetyl]amino]ethyl]-diethylazanium; 2,2'-[(1,2-dioxoethane-1,2-diyl)diimino]bis[n-(2-chlorobenzyl)-n,n-diethylethanaminium]

Indication

Disease Entry	ICD 11	Status	REF
Myasthenia gravis	8C6Y	Approved	[1]

• Therapeutic Class: Antiarrhythmic Agents
• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 3:
  Molecular Weight (mw); 537.6
  Topological Polar Surface Area (xlogp); 5.1
  Rotatable Bond Count (rotbonds); 14
  Hydrogen Bond Donor Count (hbonddonor); 2
  Hydrogen Bond Acceptor Count (hbondacc); 2
• ADMET Property: Metabolism: The drug is metabolized via plasma and hepatic [2]
• Chemical Identifiers:
  Formula: C28H42Cl2N4O2+2
  IUPAC Name: (2-chlorophenyl)methyl-[2-[[2-[2-[(2-chlorophenyl)methyl-diethylazaniumyl]ethylamino]-2-oxoacetyl]amino]ethyl]-diethylazanium
  Canonical SMILES: CC[N+](CC)(CCNC(=O)C(=O)NCC[N+](CC)(CC)CC1=CC=CC=C1Cl)CC2=CC=CC=C2Cl
  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
  InChIKey: OMHBPUNFVFNHJK-UHFFFAOYSA-P
• Cross-matching ID:
  PubChem CID: 2131
  ChEBI ID: CHEBI:2627
  CAS Number: 7648-98-8
  DrugBank ID: DB01122
  TTD ID: D06IAQ

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Acetylcholinesterase (AChE)	TT1RS9F	ACES_HUMAN	Inhibitor	[3]

Molecular Expression Atlas of This Drug

• The Studied Disease: Myasthenia gravis
• ICD Disease Classification: 8C6Y

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Acetylcholinesterase (AChE)	DTT	ACHE	6.39E-02	-1.07	-1.15

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Ambenonium (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Mepenzolate	DM8YU2F	Moderate	Antagonize the effect of Ambenonium when combined with Mepenzolate.	Digestive system disease [DE2Z]	[14]
Solifenacin	DMG592Q	Moderate	Antagonize the effect of Ambenonium when combined with Solifenacin.	Functional bladder disorder [GC50]	[14]
Belladonna	DM2RBWK	Moderate	Antagonize the effect of Ambenonium when combined with Belladonna.	Infectious gastroenteritis/colitis [1A40]	[14]
Siponimod	DM2R86O	Major	Increased risk of atrioventricular block by the combination of Ambenonium and Siponimod.	Multiple sclerosis [8A40]	[15]
Fingolimod	DM5JVAN	Moderate	Increased risk of atrioventricular block by the combination of Ambenonium and Fingolimod.	Multiple sclerosis [8A40]	[16]
Flavoxate	DMKV4NL	Moderate	Antagonize the effect of Ambenonium when combined with Flavoxate.	Pain [MG30-MG3Z]	[14]
Methylscopolamine	DM5VWOB	Moderate	Antagonize the effect of Ambenonium when combined with Methylscopolamine.	Peptic ulcer [DA61]	[14]

References

• [1] FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (NDA) 010155.
• [2] FDA approval: ado-trastuzumab emtansine for the treatment of patients with HER2-positive metastatic breast cancer. Clin Cancer Res. 2014 Sep 1;20(17):4436-41.
• [3] Alpha6-containing nicotinic acetylcholine receptors dominate the nicotine control of dopamine neurotransmission in nucleus accumbens. Neuropsychopharmacology. 2008 Aug;33(9):2158-66.
• [4] Evidence that the clinical effects of cholinesterase inhibitors are related to potency and targeting of action. Int J Clin Pract Suppl. 2002 Jun;(127):6-19.
• [5] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 2465).
• [6] Acetylcholinesterase activity in Corbicula fluminea Mull., as a biomarker of organophosphate pesticide pollution in Pinacanauan River, Philippines. Environ Monit Assess. 2010 Jun;165(1-4):331-40.
• [7] [From symptomatic to disease modifying therapy Recent developments in the pharmacotherapy of Alzheimer's disease]. Fortschr Neurol Psychiatr. 2009 Jun;77(6):326-33.
• [8] Huperzine A attenuates cognitive deficits and brain injury in neonatal rats after hypoxia-ischemia. Brain Res. 2002 Sep 13;949(1-2):162-70.
• [9] Screening of acetylcholinesterase inhibitors by CE after enzymatic reaction at capillary inlet. J Sep Sci. 2009 May;32(10):1748-56.
• [10] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [11] The effects of topical ocular application of 0.25% demecarium bromide on serum acetylcholinesterase levels in normal dogs. Vet Ophthalmol. 2003 Mar;6(1):23-5.
• [12] Rational design of alkylene-linked bis-pyridiniumaldoximes as improved acetylcholinesterase reactivators. Chem Biol. 2003 Jun;10(6):491-502.
• [13] Neuromuscular blockade, reversal agent use, and operating room time: retrospective analysis of US inpatient surgeries. Curr Med Res Opin. 2009 Apr;25(4):943-50.
• [14] Product Information. Mestinon (pyridostigmine). ICN Pharmaceuticals Inc, Cost Mesa, CA.
• [15] Cerner Multum, Inc. "Australian Product Information.".
• [16] Product Information. Gilenya (fingolimod). Novartis Pharmaceuticals, East Hanover, NJ.