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Identification
NameNeostigmine
Accession NumberDB01400
TypeSmall Molecule
GroupsApproved
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
SynonymLanguageCode
(m-Hydroxyphenyl)trimethylammonium dimethylcarbamateNot AvailableNot Available
3-Trimethylammoniumphenyl N,N-dimethylcarbamateNot AvailableNot Available
EustigminNot AvailableNot Available
EustigmineNot AvailableNot Available
m-TrimethylammoniumphenyldimethylcarbamateNot AvailableNot Available
ProstigmineNot AvailableNot Available
VagostigmineNot AvailableNot Available
Salts
Name/CAS Structure Properties
Neostigmine methylsulfate
Thumb
  • InChI Key: OSZNNLWOYWAHSS-UHFFFAOYSA-M
  • Monoisotopic Mass: 334.119857136
  • Average Mass: 334.389
DBSALT000128
Brand names
NameCompany
BloxiverzNot Available
ProstigminNot Available
VagostigminNot Available
Brand mixturesNot Available
CategoriesNot Available
CAS number59-99-4
WeightAverage: 223.2915
Monoisotopic: 223.144652862
Chemical FormulaC12H19N2O2
InChI KeyALWKGYPQUAPLQC-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
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassBenzenoids
ClassBenzene and Substituted Derivatives
SubclassPhenol Ethers
Direct parentPhenol Ethers
Alternative parentsTertiary Amines; Carbamic Acids and Derivatives; Ethers; Polyamines
Substituentscarbamic acid derivative; tertiary amine; ether; polyamine; amine; organonitrogen compound
Classification descriptionThis compound belongs to the phenol ethers. These are aromatic compounds containing an ether group substituted with a benzene ring.
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.
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
Property Value Probability
Human Intestinal Absorption - 0.8576
Blood Brain Barrier + 0.9583
Caco-2 permeable + 0.608
P-glycoprotein substrate Non-substrate 0.8263
P-glycoprotein inhibitor I Non-inhibitor 0.9598
P-glycoprotein inhibitor II Non-inhibitor 0.9279
Renal organic cation transporter Non-inhibitor 0.9181
CYP450 2C9 substrate Non-substrate 0.7197
CYP450 2D6 substrate Non-substrate 0.6869
CYP450 3A4 substrate Substrate 0.622
CYP450 1A2 substrate Non-inhibitor 0.9045
CYP450 2C9 substrate Non-inhibitor 0.907
CYP450 2D6 substrate Non-inhibitor 0.9367
CYP450 2C19 substrate Non-inhibitor 0.9025
CYP450 3A4 substrate Non-inhibitor 0.9424
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.8362
Ames test AMES toxic 0.5146
Carcinogenicity Non-carcinogens 0.5931
Biodegradation Not ready biodegradable 0.7893
Rat acute toxicity 2.9481 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.952
hERG inhibition (predictor II) Non-inhibitor 0.8738
Pharmacoeconomics
ManufacturersNot Available
Packagers
Dosage forms
FormRouteStrength
LiquidIntramuscular
LiquidIntravenous
TabletOral
Prices
Unit descriptionCostUnit
Neostigmine bromide powder96.57USDg
Neostigmine ms 5 mg/5 ml syr1.99USDml
Prostigmin 1:4000 ampul1.42USDml
Prostigmin 15 mg tablet1.04USDtablet
Neostigmine 1:1000 vial0.48USDml
Neostigmine 1:2000 vial0.48USDml
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 Solubility0.0677ALOGPS
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
Spectra
SpectraNot Available
References
Synthesis ReferenceNot Available
General ReferenceNot Available
External Links
ResourceLink
KEGG CompoundC07258
PubChem Compound4456
PubChem Substance46509161
ChemSpider4301
ChEBI7514
ChEMBLCHEMBL54126
Therapeutic Targets DatabaseDAP000563
PharmGKBPA450611
Drug Product Database868906
RxListhttp://www.rxlist.com/cgi/generic/neostigmine.htm
Drugs.comhttp://www.drugs.com/cdi/neostigmine.html
WikipediaNeostigmine
ATC CodesN07AA01S01EB06
AHFS Codes
  • 12:04.00
PDB EntriesNot Available
FDA labelNot Available
MSDSshow(74.7 KB)
Interactions
Drug Interactions
Drug
DexamethasoneThe corticosteroid, dexamethasone, may decrease the effect of the anticholinesterase, neostigmine.
FludrocortisoneThe corticosteroid, fludrocortisone, may decrease the effect of the anticholinesterase, neostigmine.
HydrocortisoneThe corticosteroid, hydrocortisone, may decrease the effect of the anticholinesterase, neostigmine.
PrednisoloneThe corticosteroid, prednisolone, may decrease the effect of the anticholinesterase, neostigmine.
PrednisoneThe corticosteroid, prednisone, may decrease the effect of the anticholinesterase, neostigmine.
TriamcinoloneThe corticosteroid, triamcinolone, may decrease the effect of the anticholinesterase, neostigmine.
Food InteractionsNot Available

Targets

1. Acetylcholinesterase

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Acetylcholinesterase P22303 Details

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
  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
  3. Takeuchi K, Kawauchi S, Araki H, Ueki S, Furukawa O: Stimulation by nizatidine, a histamine H(2)-receptor antagonist, of duodenal HCO(-)secretion in rats:relation to anti-cholinesterase activity. World J Gastroenterol. 2000 Oct;6(5):651-658. Pubmed
  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
  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
  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. Pubmed
  7. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

Enzymes

1. Cholinesterase

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Cholinesterase P06276 Details

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

Transporters

1. Multidrug resistance protein 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Multidrug resistance protein 1 P08183 Details

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

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Drug created on July 08, 2007 11:06 / Updated on September 16, 2013 17:14