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Identification
NameNeostigmine
Accession NumberDB01400
TypeSmall Molecule
GroupsApproved, Vet Approved
Description

A cholinesterase inhibitor used in the treatment of myasthenia gravis and to reverse the effects of muscle relaxants such as gallamine and tubocurarine. Neostigmine, unlike physostigmine, does not cross the blood-brain barrier. [PubChem]

Structure
Thumb
Synonyms
(m-Hydroxyphenyl)trimethylammonium dimethylcarbamate
3-Trimethylammoniumphenyl N,N-dimethylcarbamate
Eustigmin
Eustigmine
m-Trimethylammoniumphenyldimethylcarbamate
External Identifiers Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Bloxiverzinjection1 mg/mLintravenousEclat Pharmaceuticals, LLC2013-07-24Not applicableUs
Bloxiverzinjection.5 mg/mLintravenousEclat Pharmaceuticals, LLC2013-07-24Not applicableUs
Bloxiverzinjection1 mg/mLintravenousEclat Pharmaceuticals, LLC2013-07-24Not applicableUs
Bloxiverzinjection.5 mg/mLintravenousEclat Pharmaceuticals, LLC2013-07-24Not applicableUs
Neostigmine Methylsulfateinjection, solution1 mg/mLintravenousREMEDYREPACK INC.2015-10-26Not applicableUs
Neostigmine Methylsulfateinjection, solution1 mg/mLintravenousFresenius Kabi USA, LLC2015-01-08Not applicableUs
Neostigmine Methylsulfateinjection, solution.5 mg/mLintravenousFresenius Kabi USA, LLC2015-01-08Not applicableUs
Neostigmine Methylsulfate Inj 0.5mg/ml USPliquid.5 mgintramuscular; intravenous; subcutaneousDavid Bull Laboratories (Pty) Ltd.1992-12-311996-09-10Canada
Neostigmine Methylsulfate Inj 1mg/ml USPliquid1 mgintramuscular; intravenous; subcutaneousDavid Bull Laboratories (Pty) Ltd.1991-12-311996-09-10Canada
Neostigmine Methylsulfate Injectionliquid1 mgintramuscular; intravenous; subcutaneousFresenius Kabi Canada LtdNot applicableNot applicableCanada
Neostigmine Methylsulfate Injectionliquid0.5 mgintramuscular; intravenous; subcutaneousFresenius Kabi Canada LtdNot applicableNot applicableCanada
Neostigmine Methylsulfate Injection Sdzsolution2.5 mgintramuscular; intravenous; subcutaneousSandoz Canada IncorporatedNot applicableNot applicableCanada
Neostigmine Methylsulfate Injection Sdzsolution0.5 mgintramuscular; intravenous; subcutaneousSandoz Canada IncorporatedNot applicableNot applicableCanada
Neostigmine Methylsulfate Injection USPsolution2.5 mgintramuscular; intravenous; subcutaneousSandoz Canada Incorporated1991-12-31Not applicableCanada
Neostigmine Methylsulfate Injection USPliquid1 mgintramuscular; intravenous; subcutaneousSandoz Canada Incorporated1990-12-31Not applicableCanada
Neostigmine Methylsulfate Injection USPsolution0.5 mgintramuscular; intravenous; subcutaneousSandoz Canada Incorporated1990-12-31Not applicableCanada
Neostigmine Omegaliquid1 mgintramuscular; intravenous; subcutaneousOmega Laboratories Ltd1999-06-23Not applicableCanada
Neostigmine Omegasolution2.5 mgintramuscular; intravenous; subcutaneousOmega Laboratories Ltd2013-04-17Not applicableCanada
Neostigmine Omegaliquid0.5 mgintramuscular; intravenous; subcutaneousOmega Laboratories Ltd1999-05-28Not applicableCanada
PMS-neostigmine Methylsulfate Inj 0.5mg/mlliquid.5 mgintramuscular; intravenous; subcutaneousPharmascience Inc1990-12-31Not applicableCanada
PMS-neostigmine Methylsulfate Inj 1mg/mlliquid1 mgintramuscular; intravenous; subcutaneousPharmascience Inc1990-12-31Not applicableCanada
Prostigmin Inj 1:1000 USPliquid1 mgintramuscular; intravenous; subcutaneousIcn Canada Ltd.1988-12-312005-04-26Canada
Prostigmin Inj 1:2000 USPliquid.5 mgintramuscular; intravenous; subcutaneousIcn Canada Ltd.1988-12-312005-04-26Canada
Prostigmin Inj 1:400 USPsolution2.5 mgintramuscular; intravenous; subcutaneousIcn Canada Ltd.1988-12-312005-04-26Canada
Prostigmin Tabletstablet15 mgoralValeant Canada Lp Valeant Canada S.E.C.1988-12-31Not applicableCanada
Approved Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Neostigmine Methylsulfateinjection1 mg/mLintravenousWest Ward Pharmaceuticals Corp.2015-12-28Not applicableUs
Neostigmine Methylsulfateinjection.5 mg/mLintravenousWest Ward Pharmaceuticals Corp.2015-12-28Not applicableUs
Approved Over the Counter ProductsNot Available
Unapproved/Other Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Neostigmine Methylsulfateinjection, solution1 mg/mLintramuscular; intravenous; subcutaneousAmerican Regent, Inc.2003-01-16Not applicableUs
Neostigmine Methylsulfateinjection, solution1 mg/mLintravenousCantrell Drug Company2015-02-03Not applicableUs
Neostigmine Methylsulfateinjection.5 mg/mLintramuscular; intravenous; subcutaneousWest Ward Pharmaceutical Corp.1973-01-01Not applicableUs
Neostigmine Methylsulfateinjection1 mg/mLintramuscular; intravenous; subcutaneousWest Ward Pharmaceutical Corp.1973-01-01Not applicableUs
Neostigmine Methylsulfateinjection1 mg/mLintramuscular; intravenous; subcutaneousWest Ward Pharmaceutical Corp.1973-01-01Not applicableUs
Neostigmine Methylsulfateinjection.5 mg/mLintramuscular; intravenous; subcutaneousWest Ward Pharmaceutical Corp.1973-01-01Not applicableUs
Neostigmine Methylsulfateinjection, solution1 mg/mLintramuscular; intravenous; subcutaneousFresenius Kabi USA, LLC2000-09-01Not applicableUs
Neostigmine Methylsulfateinjection, solution.5 mg/mLintramuscular; intravenous; subcutaneousAmerican Regent, Inc.2003-01-17Not applicableUs
Neostigmine Methylsulfateinjection, solution5 mg/mLintramuscular; intravenous; subcutaneousFresenius Kabi USA, LLC2000-10-18Not applicableUs
International Brands
NameCompany
ProstigminNot Available
VagostigminNot Available
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Neostigmine bromide
ThumbNot applicableDBSALT001191
Neostigmine methylsulfate
Thumb
  • InChI Key: OSZNNLWOYWAHSS-UHFFFAOYSA-M
  • Monoisotopic Mass: 334.119857136
  • Average Mass: 334.389
DBSALT000128
Categories
UNII3982TWQ96G
CAS number59-99-4
WeightAverage: 223.2915
Monoisotopic: 223.144652862
Chemical FormulaC12H19N2O2
InChI KeyInChIKey=ALWKGYPQUAPLQC-UHFFFAOYSA-N
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
IUPAC Name
3-[(dimethylcarbamoyl)oxy]-N,N,N-trimethylanilinium
SMILES
CN(C)C(=O)OC1=CC(=CC=C1)[N+](C)(C)C
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as substituted anilines. These are organic compound containing an aniline group substituted at one or more positions.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassAnilines
Direct ParentSubstituted anilines
Alternative Parents
Substituents
  • Substituted aniline
  • Tertiary amine
  • Monocarboxylic acid or derivatives
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Amine
  • Organic cation
  • Aromatic homomonocyclic compound
Molecular FrameworkAromatic homomonocyclic compounds
External Descriptors
Pharmacology
IndicationNeostigmine is used for the symptomatic treatment of myasthenia gravis by improving muscle tone.
PharmacodynamicsNeostigmine is a cholinesterase inhibitor used in the treatment of myasthenia gravis and to reverse the effects of muscle relaxants such as gallamine and tubocurarine. Neostigmine, unlike physostigmine, does not cross the blood-brain barrier. By inhibiting acetylcholinesterase, more acetylcholine is available in the synapse, therefore, more of it can bind to the fewer receptors present in myasthenia gravis and can better trigger muscular contraction.
Mechanism of actionNeostigmine is a parasympathomimetic, specifically, a reversible cholinesterase inhibitor. The drug inhibits acetylcholinesterase which is responsible for the degredation of acetylcholine. So, with acetylcholinesterase inhibited, more acetylcholine is present By interfering with the breakdown of acetylcholine, neostigmine indirectly stimulates both nicotinic and muscarinic receptors which are involved in muscle contraction.. It does not cross the blood-brain barrier.
Related Articles
AbsorptionNeostigmine bromide is poorly absorbed from the gastrointestinal tract following oral administration
Volume of distributionNot Available
Protein bindingProtein binding to human serum albumin ranges from 15 to 25 percent.
Metabolism

Neostigmine undergoes hydrolysis by cholinesterase and is also metabolized by microsomal enzymes in the liver.

Route of eliminationNot Available
Half lifeThe half-life ranged from 42 to 60 minutes with a mean half-life of 52 minutes.
ClearanceNot Available
ToxicityOverdosage of Neostigmine can cause cholinergic crisis, which is characterized by increasing muscle weakness, and through involvement of the muscles of respiration, may result in death. The LD 50 of neostigmine methylsulfate in mice is 0.3 ± 0.02 mg/kg intravenously, 0.54 ± 0.03 mg/kg subcutaneously, and 0.395 ± 0.025 mg/kg intramuscularly; in rats the LD 50 is 0.315 ± 0.019 mg/kg intravenously, 0.445 ± 0.032 mg/kg subcutaneously, and 0.423 ± 0.032 mg/kg intramuscularly.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption-0.8576
Blood Brain Barrier+0.9583
Caco-2 permeable+0.608
P-glycoprotein substrateNon-substrate0.8263
P-glycoprotein inhibitor INon-inhibitor0.9598
P-glycoprotein inhibitor IINon-inhibitor0.9279
Renal organic cation transporterNon-inhibitor0.9181
CYP450 2C9 substrateNon-substrate0.7197
CYP450 2D6 substrateNon-substrate0.6869
CYP450 3A4 substrateSubstrate0.622
CYP450 1A2 substrateNon-inhibitor0.9045
CYP450 2C9 inhibitorNon-inhibitor0.907
CYP450 2D6 inhibitorNon-inhibitor0.9367
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-inhibitor0.9424
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8362
Ames testAMES toxic0.5146
CarcinogenicityNon-carcinogens0.5931
BiodegradationNot ready biodegradable0.7893
Rat acute toxicity2.9481 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.952
hERG inhibition (predictor II)Non-inhibitor0.8738
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
Packagers
Dosage forms
FormRouteStrength
Injectionintramuscular; intravenous; subcutaneous.5 mg/mL
Injectionintramuscular; intravenous; subcutaneous1 mg/mL
Injectionintravenous.5 mg/mL
Injectionintravenous1 mg/mL
Injection, solutionintramuscular; intravenous; subcutaneous.5 mg/mL
Injection, solutionintramuscular; intravenous; subcutaneous1 mg/mL
Injection, solutionintramuscular; intravenous; subcutaneous5 mg/mL
Injection, solutionintravenous.5 mg/mL
Injection, solutionintravenous1 mg/mL
Solutionintramuscular; intravenous; subcutaneous0.5 mg
Solutionintramuscular; intravenous; subcutaneous2.5 mg
Liquidintramuscular; intravenous; subcutaneous0.5 mg
Liquidintramuscular; intravenous; subcutaneous.5 mg
Liquidintramuscular; intravenous; subcutaneous1 mg
Tabletoral15 mg
Prices
Unit descriptionCostUnit
Neostigmine bromide powder96.57USD g
Neostigmine ms 5 mg/5 ml syr1.99USD ml
Prostigmin 1:4000 ampul1.42USD ml
Prostigmin 15 mg tablet1.04USD tablet
Neostigmine 1:1000 vial0.48USD ml
Neostigmine 1:2000 vial0.48USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
StateSolid
Experimental PropertiesNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.0677 mg/mLALOGPS
logP-1.6ALOGPS
logP-2.2ChemAxon
logS-3.6ALOGPS
Physiological Charge1ChemAxon
Hydrogen Acceptor Count1ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area29.54 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity75.28 m3·mol-1ChemAxon
Polarizability25.08 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis ReferenceNot Available
General ReferencesNot Available
External Links
ATC CodesN07AA01N07AA51S01EB06
AHFS Codes
  • 12:04.00
PDB EntriesNot Available
FDA labelNot Available
MSDSDownload (74.7 KB)
Interactions
Drug Interactions
Drug
AcetylcholineThe risk or severity of adverse effects can be increased when Neostigmine is combined with Acetylcholine.
Atracurium besylateNeostigmine may decrease the neuromuscular blocking activities of Atracurium besylate.
CarbacholThe risk or severity of adverse effects can be increased when Neostigmine is combined with Carbachol.
DipyridamoleThe therapeutic efficacy of Neostigmine can be decreased when used in combination with Dipyridamole.
FludrocortisoneThe risk or severity of adverse effects can be increased when Fludrocortisone is combined with Neostigmine.
NadololNeostigmine may increase the bradycardic activities of Nadolol.
ProcyclidineThe therapeutic efficacy of Procyclidine can be decreased when used in combination with Neostigmine.
SuccinylcholineThe serum concentration of Succinylcholine can be increased when it is combined with Neostigmine.
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
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
Molecular Weight:
67795.525 Da
References
  1. Trevisani GT, Hyman NH, Church JM: Neostigmine: safe and effective treatment for acute colonic pseudo-obstruction. Dis Colon Rectum. 2000 May;43(5):599-603. [PubMed:10826417 ]
  2. Naves LA, Van der Kloot W: Repetitive nerve stimulation decreases the acetylcholine content of quanta at the frog neuromuscular junction. J Physiol. 2001 May 1;532(Pt 3):637-47. [PubMed:11313435 ]
  3. Takeuchi K, Kawauchi S, Araki H, Ueki S, Furukawa O: Stimulation by nizatidine, a histamine H(2)-receptor antagonist, of duodenal HCO(3)(-)secretion in rats:relation to anti-cholinesterase activity. World J Gastroenterol. 2000 Oct;6(5):651-658. [PubMed:11819669 ]
  4. Minic J, Chatonnet A, Krejci E, Molgo J: Butyrylcholinesterase and acetylcholinesterase activity and quantal transmitter release at normal and acetylcholinesterase knockout mouse neuromuscular junctions. Br J Pharmacol. 2003 Jan;138(1):177-87. [PubMed:12522088 ]
  5. Beck KD, Brennan FX, Moldow RL, Ottenweller JE, Zhu G, Servatius RJ: Stress interacts with peripheral cholinesterase inhibitors to cause central nervous system effects. Life Sci. 2003 May 23;73(1):41-51. [PubMed:12726885 ]
  6. Zhang B, Hepner DL, Tran MH, Friedman M, Korn JR, Menzin J: 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. doi: 10.1185/03007990902769054 . [PubMed:19257799 ]
  7. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
unknown
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
Molecular Weight:
68417.575 Da
References
  1. Saito S: Cholinesterase inhibitors induce growth cone collapse and inhibit neurite extension in primary cultured chick neurons. Neurotoxicol Teratol. 1998 Jul-Aug;20(4):411-9. [PubMed:9697967 ]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Xenobiotic-transporting atpase activity
Specific Function:
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name:
ABCB1
Uniprot ID:
P08183
Molecular Weight:
141477.255 Da
References
  1. Polli JW, Wring SA, Humphreys JE, Huang L, Morgan JB, Webster LO, Serabjit-Singh CS: Rational use of in vitro P-glycoprotein assays in drug discovery. J Pharmacol Exp Ther. 2001 Nov;299(2):620-8. [PubMed:11602674 ]
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Drug created on July 08, 2007 11:06 / Updated on September 16, 2013 17:14