Identification

Name
Neostigmine
Accession Number
DB01400
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.

Type
Small Molecule
Groups
Approved, Vet approved
Structure
Thumb
Weight
Average: 223.2915
Monoisotopic: 223.144652862
Chemical Formula
C12H19N2O2
Synonyms
  • (m-Hydroxyphenyl)trimethylammonium dimethylcarbamate
  • 3-Trimethylammoniumphenyl N,N-dimethylcarbamate
  • Eustigmin
  • Eustigmine
  • m-Trimethylammoniumphenyldimethylcarbamate
  • Neostigmina

Pharmacology

Indication

Neostigmine is used for the symptomatic treatment of myasthenia gravis by improving muscle tone.

Associated Conditions
Contraindications & Blackbox Warnings
Learn about our commercial Contraindications & Blackbox Warnings data.
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Pharmacodynamics

Neostigmine 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 action

Neostigmine 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.

TargetActionsOrganism
AAcetylcholinesterase
inhibitor
Humans
Absorption

Neostigmine bromide is poorly absorbed from the gastrointestinal tract following oral administration

Volume of distribution
Not Available
Protein binding

Protein 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 elimination
Not Available
Half-life

The half-life ranged from 42 to 60 minutes with a mean half-life of 52 minutes.

Clearance
Not Available
Adverse Effects
Learn about our commercial Adverse Effects data.
Learn More
Toxicity

Overdosage 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
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AcebutololNeostigmine may increase the bradycardic activities of Acebutolol.
AcetylcholineThe risk or severity of adverse effects can be increased when Neostigmine is combined with Acetylcholine.
AclidiniumNeostigmine may increase the neuromuscular blocking activities of Aclidinium.
AmantadineThe therapeutic efficacy of Amantadine can be decreased when used in combination with Neostigmine.
AmifampridineThe risk or severity of adverse effects can be increased when Neostigmine is combined with Amifampridine.
AmitriptylineThe therapeutic efficacy of Amitriptyline can be decreased when used in combination with Neostigmine.
AmobarbitalThe therapeutic efficacy of Amobarbital can be decreased when used in combination with Neostigmine.
AmoxapineThe therapeutic efficacy of Amoxapine can be decreased when used in combination with Neostigmine.
Anisotropine methylbromideThe therapeutic efficacy of Anisotropine methylbromide can be decreased when used in combination with Neostigmine.
AripiprazoleThe therapeutic efficacy of Aripiprazole can be decreased when used in combination with Neostigmine.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

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  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level

    A rating for the strength of the evidence supporting each drug interaction.

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  • Action
    Action

    An effect category for each drug interaction. Know how this interaction affects the subject drug.

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Food Interactions
No interactions found.

Products

Product Ingredients
IngredientUNIICASInChI Key
Neostigmine bromide005SYP50G5114-80-7LULNWZDBKTWDGK-UHFFFAOYSA-M
Neostigmine methylsulfate98IMH7M38651-60-5OSZNNLWOYWAHSS-UHFFFAOYSA-M
International/Other Brands
Vagostigmin
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
BloxiverzInjection0.5 mg/1mLIntravenousAvadel Legacy Pharmaceuticals, Llc2013-07-242018-12-31US flag
BloxiverzInjection1 mg/1mLIntravenousBluePoint Laboratories2017-06-30Not applicableUS flag
BloxiverzInjection1 mg/1mLIntravenousAvadel Legacy Pharmaceuticals, Llc2013-07-24Not applicableUS flag
BloxiverzInjection1 mg/1mLIntravenousAvadel Legacy Pharmaceuticals, Llc2013-07-24Not applicableUS flag
BloxiverzInjection0.5 mg/1mLIntravenousAvadel Legacy Pharmaceuticals, Llc2013-07-24Not applicableUS flag
Neostigmine MethylsuflateInjection, solution1 mg/1mLIntramuscular; Intravenous; SubcutaneousGeneral Injectables & Vaccines2010-08-012014-08-31US flag
Neostigmine MethylsulfateInjection1 mg/1mLIntramuscular; Intravenous; SubcutaneousWest-Ward Pharmaceuticals Corp.1973-01-012015-08-31US flag
Neostigmine MethylsulfateInjection, solution0.5 mg/1mLIntramuscular; Intravenous; SubcutaneousClaris Lifesciences Limited2009-10-072010-11-04US flag
Neostigmine MethylsulfateInjection, solution5 mg/1mLIntramuscular; Intravenous; SubcutaneousFresenius Kabi2000-10-182016-11-18US flag
Neostigmine MethylsulfateInjection, solution1 mg/1mLIntravenousGeneral Injectables and Vaccines, Inc2016-08-112018-12-31US flag
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
NeostigmineInjection1 mg/1mLIntravenousMedical Purchasing Solutions, Llc2018-09-04Not applicableUS flag
NeostigmineInjection1 mg/1mLIntravenousDr.Reddy's Laboratories Inc2018-09-04Not applicableUS flag
NeostigmineInjection0.5 mg/1mLIntravenousDr.Reddy's Laboratories Inc2018-09-04Not applicableUS flag
Neostigmine methylsulfateInjection1 mg/1mLIntravenousBE Pharmaceuticals Inc.2019-05-13Not applicableUS flag
Neostigmine MethylsulfateInjection1 mg/1mLIntravenousHikma Pharmaceuticals USA Inc.2015-12-28Not applicableUS flag
Neostigmine MethylsulfateInjection1 mg/1mLIntravenousMedical Purchasing Solutions, Llc2017-04-26Not applicableUS flag
Neostigmine MethylsulfateInjection1 mg/1mLIntravenousA-S Medication Solutions2017-09-25Not applicableUS flag
Neostigmine MethylsulfateInjection0.5 mg/1mLIntravenousAMERICAN REGENT, INC.2018-05-14Not applicableUS flag
Neostigmine methylsulfateInjection0.5 mg/1mLIntravenousXiromed Llc2020-09-09Not applicableUS flag
Neostigmine MethylsulfateInjection0.5 mg/1mLIntravenousRenaissance Ssa, Llc2019-12-312019-12-31US flag
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

    Learn more
  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

    Learn more
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
Neostigmine MethylsuflateNeostigmine methylsulfate (1 mg/1mL)Injection, solutionIntramuscular; Intravenous; SubcutaneousGeneral Injectables & Vaccines2010-08-012014-08-31US flag
Neostigmine MethylsulfateNeostigmine methylsulfate (1 mg/1mL)InjectionIntramuscular; Intravenous; SubcutaneousWest-Ward Pharmaceuticals Corp.1973-01-012015-08-31US flag
Neostigmine MethylsulfateNeostigmine methylsulfate (0.5 mg/1mL)Injection, solutionIntramuscular; Intravenous; SubcutaneousClaris Lifesciences Limited2009-10-072010-11-04US flag
Neostigmine MethylsulfateNeostigmine methylsulfate (5 mg/1mL)Injection, solutionIntramuscular; Intravenous; SubcutaneousFresenius Kabi2000-10-182016-11-18US flag
Neostigmine MethylsulfateNeostigmine methylsulfate (0.5 mg/1mL)Injection, solutionIntramuscular; Intravenous; SubcutaneousAmerican Regent2003-01-172016-10-17US flag
Neostigmine MethylsulfateNeostigmine methylsulfate (1 mg/1mL)InjectionIntramuscular; Intravenous; SubcutaneousWest-Ward Pharmaceuticals Corp.1973-01-012016-08-31US flag
Neostigmine MethylsulfateNeostigmine methylsulfate (1 mg/1mL)Injection, solutionIntramuscular; Intravenous; SubcutaneousAmerican Regent2003-01-162016-10-17US flag
Neostigmine MethylsulfateNeostigmine methylsulfate (0.5 mg/1mL)InjectionIntramuscular; Intravenous; SubcutaneousWest-Ward Pharmaceuticals Corp.1973-01-012015-09-30US flag
Neostigmine MethylsulfateNeostigmine methylsulfate (1 mg/1mL)Injection, solutionIntramuscular; Intravenous; SubcutaneousClaris Lifesciences, Inc.2009-10-092010-11-04US flag
Neostigmine MethylsulfateNeostigmine methylsulfate (1 mg/1mL)InjectionIntramuscular; Intravenous; SubcutaneousCardinal Health1973-01-012014-09-30US flag

Categories

ATC Codes
N07AA01 — NeostigmineS01EB06 — NeostigmineN07AA51 — Neostigmine, combinations
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as phenoxy compounds. These are aromatic compounds contaning a phenoxy group.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Phenoxy compounds
Direct Parent
Phenoxy compounds
Alternative Parents
Aniline and substituted anilines / Quaternary ammonium salts / Carbamate esters / Organic carbonic acids and derivatives / Organopnictogen compounds / Organic salts / Organic oxides / Hydrocarbon derivatives / Carbonyl compounds / Amines
show 1 more
Substituents
Amine / Aniline or substituted anilines / Aromatic homomonocyclic compound / Carbamic acid ester / Carbonic acid derivative / Carbonyl group / Hydrocarbon derivative / Organic cation / Organic nitrogen compound / Organic oxide
show 7 more
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
quaternary ammonium ion (CHEBI:7514)

Chemical Identifiers

UNII
3982TWQ96G
CAS number
59-99-4
InChI Key
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

References

General References
Not Available
Human Metabolome Database
HMDB0015472
KEGG Drug
D08261
KEGG Compound
C07258
PubChem Compound
4456
PubChem Substance
46509161
ChemSpider
4301
BindingDB
50022775
RxNav
7315
ChEBI
7514
ChEMBL
CHEMBL278020
ZINC
ZINC000000001792
Therapeutic Targets Database
DAP000563
PharmGKB
PA450611
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Neostigmine
AHFS Codes
  • 12:04.00 — Parasympathomemetic (Cholinergic) Agents
MSDS
Download (74.7 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4Active Not RecruitingPreventionResidual Paralysis, Post Anesthesia1
4Active Not RecruitingSupportive CareCancer, Bladder / Malignant Neoplasms of Urinary Tract1
4Active Not RecruitingSupportive CareMuscle Relaxation1
4Active Not RecruitingTreatmentAnaesthesia therapy / Neuromuscular Blockade1
4Active Not RecruitingTreatmentMalignant Neoplasms of Digestive Organs / Malignant Neoplasms of Female Genital Organs / Malignant Neoplasms of Male Genital Organs / Malignant Neoplasms of Urinary Tract1
4CompletedBasic ScienceElectromyography / Respiratory Muscles1
4CompletedDiagnosticIntraocular Pressure Changes During Tracheal Extubation1
4CompletedDiagnosticResidual Neuromuscular Block1
4CompletedDiagnosticSphincter of Oddi Dysfunction1
4CompletedDiagnosticSpinal Cord Injuries (SCI)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • American Regent
  • Pharmedium
  • Spectrum Pharmaceuticals
  • Valeant Ltd.
Dosage Forms
FormRouteStrength
InjectionIntravenous0.5 mg/1mL
InjectionIntravenous1 mg/1mL
Injection, solutionParenteral0.5 MG/ML
Injection, solutionIntramuscular; Intravenous; Subcutaneous0.5 mg/ml
Injection0.5 mg/ml
SolutionIntramuscular; Intravenous0.5 mg
SolutionIntramuscular; Intravenous; Subcutaneous0.5 mg
InjectionIntramuscular; Intravenous; Subcutaneous0.5 mg/1mL
InjectionIntramuscular; Intravenous; Subcutaneous1 mg/1mL
Injection, solutionIntramuscular; Intravenous; Subcutaneous0.5 mg/1mL
Injection, solutionIntramuscular; Intravenous; Subcutaneous1 mg/1mL
Injection, solutionIntramuscular; Intravenous; Subcutaneous5 mg/1mL
Injection, solutionIntravenous0.5 mg/1mL
Injection, solutionIntravenous1 mg/1mL
SolutionIntramuscular; Intravenous; Subcutaneous
LiquidIntramuscular; Intravenous; Subcutaneous
TabletOral15 mg/1
TabletOral
Injection0.5 mg/1ml
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.
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not 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 FilterNoChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
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)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-00di-0090000000-7feec7180feed2165741
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-00di-0090000000-33ad4a0e0807f82bab39
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-0ab9-2090000000-285ee2bce4f4c2097510
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-00di-9110000000-a2386202e9dc8c7c753f
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-00di-9100000000-b80120a3f55bb762fe51
LC-MS/MS Spectrum - LC-ESI-IT , positiveLC-MS/MSsplash10-0a4i-0090000000-675c3ee4663579ce2125

Targets

Details
1. Acetylcholinesterase
Kind
Protein
Organism
Humans
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
Uniprot Name
Acetylcholinesterase
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
Humans
Pharmacological action
Unknown
Actions
Inhibitor
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
Uniprot Name
Cholinesterase
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]

Drug created on July 08, 2007 11:06 / Updated on September 27, 2020 08:17

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