Details of the Drug

General Information of Drug (ID: DMCRQHB)

• Drug Name: Edrophonium
• Synonyms: EDR; Edrophonum; Edroponium; Reversol; Tensilon; EDROPHONIUM ION; Edrophone Chloride; Enlon Plus; ENLON-PLUS; Enlon (TN); Reversol (TN); Tensilon (TN); Ethyl-(3-hydroxyphenyl)-dimethylazanium; Ethyl-(3-hydroxy-phenyl)-dimethyl-ammonium; N-ethyl-3-hydroxy-N,N-dimethylanilinium; N-ethyl-3-hydroxy-N,N-dimethylbenzenaminium; (3-hydroxyphenyl)dimethylethylammonium; 3-hydroxy-N,N-dimethyl-N-ethylanilinium

Indication

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

• Therapeutic Class: Antidotes
• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 166.24
  Topological Polar Surface Area (xlogp); 1.8
  Rotatable Bond Count (rotbonds); 2
  Hydrogen Bond Donor Count (hbonddonor); 1
  Hydrogen Bond Acceptor Count (hbondacc); 1
• ADMET Property:
  Absorption: The drug is rapidly absorbed [2]
  Clearance: The drug present in the plasma can be removed from the body at the rate of 9.6 mL/min/kg [3]
  Half-life: The concentration or amount of drug in body reduced by one-half in 33 - 110 minutes [3]
  Vd: The volume of distribution (Vd) of drug is 1.6 +/- 0.4 L/kg [4]
• Chemical Identifiers:
  Formula: C10H16NO+
  IUPAC Name: ethyl-(3-hydroxyphenyl)-dimethylazanium
  Canonical SMILES: CC[N+](C)(C)C1=CC(=CC=C1)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
  InChIKey: VWLHWLSRQJQWRG-UHFFFAOYSA-O
• Cross-matching ID:
  PubChem CID: 3202
  ChEBI ID: CHEBI:251408
  CAS Number: 312-48-1
  DrugBank ID: DB01010
  TTD ID: D0S5LH

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Acetylcholinesterase (AChE)	TT1RS9F	ACES_HUMAN	Inhibitor	[5], [6], [7]

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 Same Disease as Edrophonium

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Disease	REF
Neostigmine	DM6T2J3	Moderate	Additive cholinergic effects by the combination of Edrophonium and Neostigmine.	Myasthenia gravis [8C6Y]	[17]

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

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Bethanechol	DMCLHO0	Moderate	Additive cholinergic effects by the combination of Edrophonium and Bethanechol.	Abnormal micturition [MF50]	[17]
Mepenzolate	DM8YU2F	Moderate	Antagonize the effect of Edrophonium when combined with Mepenzolate.	Digestive system disease [DE2Z]	[18]
Oxybutynine	DMJPBAX	Moderate	Antagonize the effect of Edrophonium when combined with Oxybutynine.	Discovery agent [N.A.]	[18]
Solifenacin	DMG592Q	Moderate	Antagonize the effect of Edrophonium when combined with Solifenacin.	Functional bladder disorder [GC50]	[18]
Tolterodine	DMSHPW8	Moderate	Antagonize the effect of Edrophonium when combined with Tolterodine.	Functional bladder disorder [GC50]	[18]
Belladonna	DM2RBWK	Moderate	Antagonize the effect of Edrophonium when combined with Belladonna.	Infectious gastroenteritis/colitis [1A40]	[18]
Thalidomide	DM70BU5	Moderate	Increased risk of ventricular arrhythmias by the combination of Edrophonium and Thalidomide.	Multiple myeloma [2A83]	[19]
Siponimod	DM2R86O	Major	Increased risk of atrioventricular block by the combination of Edrophonium and Siponimod.	Multiple sclerosis [8A40]	[19]
Fingolimod	DM5JVAN	Moderate	Increased risk of bradycardia by the combination of Edrophonium and Fingolimod.	Multiple sclerosis [8A40]	[20]
Ozanimod	DMT6AM2	Moderate	Increased risk of atrioventricular block by the combination of Edrophonium and Ozanimod.	Multiple sclerosis [8A40]	[21]
Flavoxate	DMKV4NL	Moderate	Antagonize the effect of Edrophonium when combined with Flavoxate.	Pain [MG30-MG3Z]	[18]
Methylscopolamine	DM5VWOB	Moderate	Antagonize the effect of Edrophonium when combined with Methylscopolamine.	Peptic ulcer [DA61]	[18]
Procainamide	DMNMXR8	Moderate	Antagonize the effect of Edrophonium when combined with Procainamide.	Ventricular tachyarrhythmia [BC71]	[18]

References

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• [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] Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
• [4] An FDA phase I clinical trial of quinacrine sterilization (QS). Int J Gynaecol Obstet. 2003 Oct;83 Suppl 2:S45-9.
• [5] Screening of acetylcholinesterase inhibitors by CE after enzymatic reaction at capillary inlet. J Sep Sci. 2009 May;32(10):1748-56.
• [6] 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.
• [7] Stabilization of Torpedo californica acetylcholinesterase by reversible inhibitors. Biochemistry. 2009 Jan 27;48(3):563-74.
• [8] 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.
• [9] 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).
• [10] 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.
• [11] [From symptomatic to disease modifying therapy Recent developments in the pharmacotherapy of Alzheimer's disease]. Fortschr Neurol Psychiatr. 2009 Jun;77(6):326-33.
• [12] Huperzine A attenuates cognitive deficits and brain injury in neonatal rats after hypoxia-ischemia. Brain Res. 2002 Sep 13;949(1-2):162-70.
• [13] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [14] Alpha6-containing nicotinic acetylcholine receptors dominate the nicotine control of dopamine neurotransmission in nucleus accumbens. Neuropsychopharmacology. 2008 Aug;33(9):2158-66.
• [15] 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.
• [16] Rational design of alkylene-linked bis-pyridiniumaldoximes as improved acetylcholinesterase reactivators. Chem Biol. 2003 Jun;10(6):491-502.
• [17] Product Information. Aricept (donepezil). Pfizer US Pharmaceuticals, New York, NY.
• [18] Product Information. Mestinon (pyridostigmine). ICN Pharmaceuticals Inc, Cost Mesa, CA.
• [19] Cerner Multum, Inc. "Australian Product Information.".
• [20] Product Information. Gilenya (fingolimod). Novartis Pharmaceuticals, East Hanover, NJ.
• [21] Product Information. Zeposia (ozanimod). Celgene Corporation, Summit, NJ.