Details of the Drug

General Information of Drug (ID: DM6T2J3)

• Drug Name: Neostigmine
• Synonyms: Eustigmin; Eustigmine; Intrastigmina; Juvastigmin; Neostigmin; Neostigminum; Prostigmin; Prostigmine; Prozerin; Sulfonatooxymethane; Synstigmin; Syntostigmine; Vagostigmin; Vagostigmine; Neostigmine [BAN]; Neostigmine omega; M-Trimethylammoniumphenyldimethylcarbamate; Neostigmine (BAN); Prostigmin (TN); Vagostigmin (TN); [3-(dimethylcarbamoyloxy)phenyl]-trimethylazanium; [3-(dimethylcarbamoyloxy)phenyl]-trimethyl-azanium; [3-(dimethylcarbamoyloxy)phenyl]-trimethyl-azanium bromide; Ammonium, (m-hydroxyphenyl)trimethyl-, dimethylcarbamate (ester); Benzenaminium, 3-(((dimethylamino)carbonyl)oxy)-N,N,N-trimethyl-(9CI); (m-Hydroxyphenyl)trimethylammonium dimethylcarbamate; (m-Hydroxyphenyl)trimethylammonium dimethylcarbamate (ester); 3-Trimethylammoniumphenyl N,N-dimethylcarbamate; 3-[(dimethylcarbamoyl)oxy]-N,N,N-trimethylanilinium; 3-{[(dimethylamino)carbonyl]oxy}-N,N,N-trimethylanilinium

Indication

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

• Therapeutic Class: Parasympathomimetics
• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 223.29
  Topological Polar Surface Area (xlogp); 1.5
  Rotatable Bond Count (rotbonds); 3
  Hydrogen Bond Donor Count (hbonddonor); 0
  Hydrogen Bond Acceptor Count (hbondacc); 2
• ADMET Property:
  BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 3: high solubility and low permeability [2]
  Clearance: The drug present in the plasma can be removed from the body at the rate of 9.2 mL/min/kg [3]
  Elimination: 67% of drug is excreted from urine in the unchanged form [2]
  Half-life: The concentration or amount of drug in body reduced by one-half in 42 - 60 minutes [3]
  Metabolism: The drug is metabolized via the cholinesterase and is also metabolized by microsomal enzymes in the liver [4]
  MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 0.1178 micromolar/kg/day [5]
  Vd: Fluid volume that would be required to contain the amount of drug present in the body at the same concentration as in the plasma 0.74 L/kg [3]
  Water Solubility: The ability of drug to dissolve in water is measured as 100 mg/mL [2]
• Chemical Identifiers:
  Formula: C12H19N2O2+
  IUPAC Name: [3-(dimethylcarbamoyloxy)phenyl]-trimethylazanium
  Canonical SMILES: CN(C)C(=O)OC1=CC=CC(=C1)[N+](C)(C)C
  InChI: InChI=1S/C12H19N2O2/c1-13(2)12(15)16-11-8-6-7-10(9-11)14(3,4)5/h6-9H,1-5H3/q+1
  InChIKey: ALWKGYPQUAPLQC-UHFFFAOYSA-N
• Cross-matching ID:
  PubChem CID: 4456
  ChEBI ID: CHEBI:7514
  CAS Number: 59-99-4
  DrugBank ID: DB01400
  TTD ID: D08USJ
  VARIDT ID: DR01375
  ACDINA ID: D01279

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

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

Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[8]

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
P-glycoprotein 1 (ABCB1)	DTP	P-GP	6.54E-01	1.95E-01	4.04E-01

Drug-Drug Interaction (DDI) Information of This Drug

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

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Paromomycin	DM1AGXN	Moderate	Additive neuromuscular blocking effects by the combination of Neostigmine and Paromomycin.	Amoebiasis [1A36]	[25]
Mepenzolate	DM8YU2F	Moderate	Antagonize the effect of Neostigmine when combined with Mepenzolate.	Digestive system disease [DE2Z]	[26]
Solifenacin	DMG592Q	Moderate	Antagonize the effect of Neostigmine when combined with Solifenacin.	Functional bladder disorder [GC50]	[26]
Belladonna	DM2RBWK	Moderate	Antagonize the effect of Neostigmine when combined with Belladonna.	Infectious gastroenteritis/colitis [1A40]	[26]
Polyethylene glycol	DM4I1JP	Moderate	Increased risk of lowers seizure threshold by the combination of Neostigmine and Polyethylene glycol.	Irritable bowel syndrome [DD91]	[27]
Siponimod	DM2R86O	Major	Increased risk of atrioventricular block by the combination of Neostigmine and Siponimod.	Multiple sclerosis [8A40]	[28]
Fingolimod	DM5JVAN	Moderate	Increased risk of atrioventricular block by the combination of Neostigmine and Fingolimod.	Multiple sclerosis [8A40]	[29]
Ozanimod	DMT6AM2	Moderate	Increased risk of atrioventricular block by the combination of Neostigmine and Ozanimod.	Multiple sclerosis [8A40]	[30]
Methylscopolamine	DM5VWOB	Moderate	Antagonize the effect of Neostigmine when combined with Methylscopolamine.	Peptic ulcer [DA61]	[26]
Plazomicin	DMKMBES	Moderate	Additive neuromuscular blocking effects by the combination of Neostigmine and Plazomicin.	Urinary tract infection [GC08]	[25]

Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG

DIG Name	DIG ID	PubChem CID	Functional Classification
Phenol	E00038	996	Antimicrobial preservative
Sodium acetate	E00431	517045	Antimicrobial preservative; Buffering agent; Flavoring agent
Water	E00035	962	Solvent

Pharmaceutical Formulation

Formulation Name	Drug Dosage	Dosage Form	Route
Neostigmine 3mg/3ml solution	3mg/3ml	Solution	Intravenous
Neostigmine 5mg/10ml solution	5mg/10ml	Solution	Intravenous
Neostigmine 10mg/10ml solution	10mg/10ml	Solution	Intravenous

Jump to Detail Pharmaceutical Formulation Page of This Drug

References

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• [16] 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.
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• [23] 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.
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• [27] Product Information. Suprep Bowel Prep Kit (magnesium/potassium/sodium sulfates). Braintree Laboratories, Braintree, MA.
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• [29] Product Information. Gilenya (fingolimod). Novartis Pharmaceuticals, East Hanover, NJ.
• [30] Product Information. Zeposia (ozanimod). Celgene Corporation, Summit, NJ.