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]
Urinary retention	MF50.3	Approved	[2]
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Therapeutic Class

Parasympathomimetics

Affected Organisms

Humans and other mammals

ATC Code

N07AA01: Neostigmine

N07AA: Anticholinesterases

N07A: PARASYMPATHOMIMETICS

N07: OTHER NERVOUS SYSTEM DRUGS

N: NERVOUS SYSTEM

N07AA01: Neostigmine

N07AA: Anticholinesterases

N07A: PARASYMPATHOMIMETICS

N07: OTHER NERVOUS SYSTEM DRUGS

N: NERVOUS SYSTEM

S01EB06: Neostigmine

S01EB: Parasympathomimetics

S01E: ANTIGLAUCOMA PREPARATIONS AND MIOTICS

S01: OPHTHALMOLOGICALS

S: SENSORY ORGANS

S01EB06: Neostigmine

S01EB: Parasympathomimetics

S01E: ANTIGLAUCOMA PREPARATIONS AND MIOTICS

S01: OPHTHALMOLOGICALS

S: SENSORY ORGANS

Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 0

Molecular Weight (mw)

223.29

Logarithm of the Partition Coefficient (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 [3]
Clearance: The drug present in the plasma can be removed from the body at the rate of 9.2 mL/min/kg [4]
Elimination: 67% of drug is excreted from urine in the unchanged form [3]
Half-life: The concentration or amount of drug in body reduced by one-half in 42 - 60 minutes [4]
Metabolism: The drug is metabolized via the cholinesterase and is also metabolized by microsomal enzymes in the liver []
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 [4]
Water Solubility: The ability of drug to dissolve in water is measured as 100 mg/mL [3]

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
UNII: 3982TWQ96G
DrugBank ID: DB01400
TTD ID: D08USJ
VARIDT ID: DR01375
ACDINA ID: D01279

Combinatorial Drugs (CBD)

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Repurposed Drugs (RPD)

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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]

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Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[7]

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Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Acetylcholinesterase (ACHE)	OT2H8HG6	ACES_HUMAN	Gene/Protein Processing	[8]
Cholinesterase (BCHE)	OTOH3WQ9	CHLE_HUMAN	Drug Response	[9]

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Molecular Interaction Atlas (MIA)

MIA Detail

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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

Molecular Expression Atlas (MEA)

MEA Detail

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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]	[10]
Mepenzolate	DM8YU2F	Moderate	Antagonize the effect of Neostigmine when combined with Mepenzolate.	Digestive system disease [DE2Z]	[11]
Solifenacin	DMG592Q	Moderate	Antagonize the effect of Neostigmine when combined with Solifenacin.	Functional bladder disorder [GC50]	[11]
Belladonna	DM2RBWK	Moderate	Antagonize the effect of Neostigmine when combined with Belladonna.	Infectious gastroenteritis/colitis [1A40]	[11]
Polyethylene glycol	DM4I1JP	Moderate	Increased risk of lowers seizure threshold by the combination of Neostigmine and Polyethylene glycol.	Irritable bowel syndrome [DD91]	[12]
Siponimod	DM2R86O	Major	Increased risk of atrioventricular block by the combination of Neostigmine and Siponimod.	Multiple sclerosis [8A40]	[13]
Fingolimod	DM5JVAN	Moderate	Increased risk of atrioventricular block by the combination of Neostigmine and Fingolimod.	Multiple sclerosis [8A40]	[14]
Ozanimod	DMT6AM2	Moderate	Increased risk of atrioventricular block by the combination of Neostigmine and Ozanimod.	Multiple sclerosis [8A40]	[15]
Methylscopolamine	DM5VWOB	Moderate	Antagonize the effect of Neostigmine when combined with Methylscopolamine.	Peptic ulcer [DA61]	[11]
Plazomicin	DMKMBES	Moderate	Additive neuromuscular blocking effects by the combination of Neostigmine and Plazomicin.	Urinary tract infection [GC08]	[10]
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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
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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

1	Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
2	Neostigmine FDA Label
3	BDDCS applied to over 900 drugs
4	Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
5	Estimating the safe starting dose in phase I clinical trials and no observed effect level based on QSAR modeling of the human maximum recommended daily dose
6	Screening of acetylcholinesterase inhibitors by CE after enzymatic reaction at capillary inlet. J Sep Sci. 2009 May;32(10):1748-56.
7	Improving the prediction of the brain disposition for orally administered drugs using BDDCS. Adv Drug Deliv Rev. 2012 Jan;64(1):95-109.
8	Hairy-root organ cultures for the production of human acetylcholinesterase. BMC Biotechnol. 2008 Dec 23;8:95.
9	Fresh frozen plasma transfusion for reversal of prolonged post-anaesthesia apnoea. Transfus Med. 2008 Apr;18(2):134-6. doi: 10.1111/j.1365-3148.2008.00851.x.
10	Burkett L, Bikhazi GB, Thomas KC Jr, Rosenthal DA, Wirta MG, Foldes FF "Mutual potentiation of the neuromuscular effects of antibiotics and relaxants." Anesth Analg 58 (1979): 107-15. [PMID: 571233]
11	Product Information. Mestinon (pyridostigmine). ICN Pharmaceuticals Inc, Cost Mesa, CA.
12	Product Information. Suprep Bowel Prep Kit (magnesium/potassium/sodium sulfates). Braintree Laboratories, Braintree, MA.
13	Cerner Multum, Inc. "Australian Product Information.".
14	Product Information. Gilenya (fingolimod). Novartis Pharmaceuticals, East Hanover, NJ.
15	Product Information. Zeposia (ozanimod). Celgene Corporation, Summit, NJ.