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Identification
Name Neostigmine
Accession Number DB01400
Type small molecule
Groups 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
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms Not Available
Salts
  • Neostigmine methylsulfate
Brand names
Name Company
Neostigmine omega
Prostigmin
Brand mixtures Not Available
Categories
  • Parasympathomimetics
  • Cholinesterase Inhibitors
CAS number 59-99-4
Weight Average: 223.2915
Monoisotopic: 223.144652862
Chemical Formula C12H19N2O2
InChI Key InChIKey=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
Plain Text
IUPAC Name
3-[(dimethylcarbamoyl)oxy]-N,N,N-trimethylanilinium
SMILES
CN(C)C(=O)OC1=CC(=CC=C1)[N+](C)(C)C
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Carbamates and Derivatives
  • Phenols and Derivatives
  • Anisoles
  • Phenyl Esters
  • Anilines
Substructures
  • Carbamates and Derivatives
  • Phenols and Derivatives
  • Ethers
  • Benzene and Derivatives
  • Quaternary Ammonium Salts
  • Aromatic compounds
  • Anisoles
  • Phenyl Esters
  • Anilines
  • Cations
Pharmacology
Indication Neostigmine is used for the symptomatic treatment of myasthenia gravis by improving muscle tone.
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.
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
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
Pharmacoeconomics
Manufacturers Not Available
Packagers
Dosage forms
Form Route Strength
Liquid Intramuscular
Liquid Intravenous
Tablet Oral
Prices
Unit description Cost Unit
Neostigmine bromide powder 96.57 USD g
Neostigmine ms 5 mg/5 ml syr 1.99 USD ml
Prostigmin 1:4000 ampul 1.42 USD ml
Prostigmin 15 mg tablet 1.04 USD tablet
Neostigmine 1:1000 vial 0.48 USD ml
Neostigmine 1:2000 vial 0.48 USD 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
Property Value Source
water solubility 6.77e-02 g/l ALOGPS
logP -1.6 ALOGPS
logP -2.2 ChemAxon
logS -3.6 ALOGPS
physiological charge 1 ChemAxon
hydrogen acceptor count 1 ChemAxon
hydrogen donor count 0 ChemAxon
polar surface area 29.54 ChemAxon
rotatable bond count 3 ChemAxon
refractivity 75.28 ChemAxon
polarizability 25.08 ChemAxon
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Compound C07258 Link_out
PubChem Compound 4456 Link_out
PubChem Substance 46509161 Link_out
ChemSpider 4301 Link_out
ChEBI 7514 Link_out
ChEMBL 7514 Link_out
Therapeutic Targets Database DAP000563 Link_out
PharmGKB PA450611 Link_out
Drug Product Database 868906 Link_out
RxList http://www.rxlist.com/cgi/generic/neostigmine.htm Link_out
Drugs.com http://www.drugs.com/cdi/neostigmine.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Neostigmine Link_out
ATC Codes
  • N07AA01
  • S01EB06
AHFS Codes
  • 12:04.00
PDB Entries Not Available
FDA label Not Available
MSDS show (74.7 KB)
Interactions
Drug Interactions
Drug Interaction
Dexamethasone The corticosteroid, dexamethasone, may decrease the effect of the anticholinesterase, neostigmine.
Fludrocortisone The corticosteroid, fludrocortisone, may decrease the effect of the anticholinesterase, neostigmine.
Hydrocortisone The corticosteroid, hydrocortisone, may decrease the effect of the anticholinesterase, neostigmine.
Prednisolone The corticosteroid, prednisolone, may decrease the effect of the anticholinesterase, neostigmine.
Prednisone The corticosteroid, prednisone, may decrease the effect of the anticholinesterase, neostigmine.
Triamcinolone The corticosteroid, triamcinolone, may decrease the effect of the anticholinesterase, neostigmine.
Food Interactions Not Available
Targets

1. Acetylcholinesterase

Pharmacological action: yes
Actions: inhibitor

Rapidly hydrolyzes choline released into the synapse

Organism class: human
UniProt ID: P22303 Link_out
Gene: ACHE Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

An acylcholine + H(2)O = choline + a carboxylate

UniProt ID: P06276 Link_out
Gene: BCHE Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Actions: inhibitor

Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells

UniProt ID: P08183 Link_out
Gene: ABCB1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
Comments
Drug created on July 08, 2007 11:06 / Updated on February 08, 2013 16:20