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Identification
Name Isoflurophate
Accession Number DB00677 (APRD00763)
Type small molecule
Groups approved
Description

An irreversible cholinesterase inhibitor with actions similar to those of echothiophate. It is a powerful miotic used mainly in the treatment of glaucoma. Its vapor is highly toxic and it is recommended that only solutions in arachis oil be used therapeutically. (From Martindale, The Extra Pharmacopoeia, 29th ed, p1330)
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
DFP
Diflupyl
Diflurophate
Diisopropoxyphosphoryl Fluoride
Salts Not Available
Brand names
Name Company
Diisopropyl Fluoridophosphate
Diisopropyl Fluorophosphate
Diisopropyl Fluorophosphonate
Diisopropyl Phosphofluoridate
Diisopropyl Phosphorofluoridate
Diisopropylfluorfosfat
Disiopropyl Fluorophosphonate
Dyflos
Floropryl
Fluorodiisopropyl Phosphate
Fluoropryl
Fluostigmine
Fluropryl
Humorsol
Isofluorophate
Isofluorphate
Isoflurophosphate
Isopropyl Fluophosphate
Isopropyl Phosphorofluoridate
Neoglaucit
O,O-Diisopropyl Fluorophosphate
PF-3
First Prev Next Last
Brand mixtures Not Available
Categories
  • Protease Inhibitors
  • Cholinesterase Inhibitors
  • Miotics
  • Antiglaucomic Agents
  • Ophthalmics
CAS number 55-91-4
Weight Average: 184.1457
Monoisotopic: 184.066459031
Chemical Formula C6H14FO3P
InChI Key InChIKey=MUCZHBLJLSDCSD-UHFFFAOYSA-N
InChI
InChI=1S/C6H14FO3P/c1-5(2)9-11(7,8)10-6(3)4/h5-6H,1-4H3
Plain Text
IUPAC Name
bis(propan-2-yl) fluorophosphonate
SMILES
CC(C)OP(F)(=O)OC(C)C
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Acyl Phosphates
  • Organophosphate Esters
Substructures
  • Acyl Phosphates
  • Phosphonic Acids and Derivatives
  • Organophosphate Esters
  • Phosphinic Acids and Derivatives
  • Phosphoric Acids and Derivatives
Pharmacology
Indication For use in the eye to treat certain types of glaucoma and other eye conditions, such as accommodative esotropia.
Pharmacodynamics Isoflurophate is used as ocular drops in the treatment of chronic glaucoma. Isoflurophate is an organophosphorus compound that acts as an irreversible cholinesterase inhibitor. As such, it displays parasympathomimetic effects. Isoflurophate is used in the eye to treat certain types of glaucoma and other eye conditions, such as accommodative esotropia. They may also be used in the diagnosis of certain eye conditions, such as accommodative esotropia. Isoflurophate damages the acetylcholinesterase enzyme and is therefore irreversible, however, pralidoxime can displace organophosphates such as isoflurophate from acetylcholinesterase, but only if administered before isoflurophate damages (alkylates) the enzyme.
Mechanism of action The mechanism of isoflurophate's action involves the irreversible inhibition of cholinesterase.
Absorption Not Available
Volume of distribution Not Available
Protein binding Not Available
Metabolism Not Available
Route of elimination Not Available
Half life Not Available
Clearance Not Available
Toxicity Signs of overdose include increased sweating, loss of bladder control, muscle weakness, nausea, vomiting, diarrhea, or stomach cramps or pain, shortness of breath, tightness in chest, or wheezing, slow or irregular heartbeat, unusual tiredness or weakness, watering of mouth.
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Merck and co inc
Packagers Not Available
Dosage forms Not Available
Prices Not Available
Patents Not Available
Properties
State liquid
Experimental Properties
Property Value Source
melting point -82 °C PhysProp
boiling point 183 °C PhysProp
water solubility 1.54E+004 mg/L (at 25 °C) MERCK INDEX (1996)
logP 1.17 CZERWINSKI,SE ET AL. (1998)
Predicted Properties
Property Value Source
water solubility 6.78e+00 g/l ALOGPS
logP 1.1 ALOGPS
logP 1.76 ChemAxon
logS -1.4 ALOGPS
pKa (strongest basic) -9.6 ChemAxon
physiological charge 0 ChemAxon
hydrogen acceptor count 1 ChemAxon
hydrogen donor count 0 ChemAxon
polar surface area 35.53 ChemAxon
rotatable bond count 4 ChemAxon
refractivity 40.89 ChemAxon
polarizability 16.75 ChemAxon
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Drug D00043 Link_out
KEGG Compound C00202 Link_out
PubChem Compound 5936 Link_out
PubChem Substance 46504499 Link_out
ChemSpider 5723 Link_out
ChEBI 17941 Link_out
ChEMBL 17941 Link_out
Therapeutic Targets Database DAP000896 Link_out
PharmGKB PA164748933 Link_out
Wikipedia http://en.wikipedia.org/wiki/Isoflurophate Link_out
ATC Codes Not Available
AHFS Codes Not Available
PDB Entries Not Available
FDA label Not Available
MSDS show (57.7 KB)
Interactions
Drug Interactions Not Available
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. Malatova Z, Gottlieb M, Marsala J: Depression of acetylcholinesterase synthesis following transient cerebral ischemia in rat: pharmacohistochemical and biochemical investigation. Gen Physiol Biophys. 1999 Mar;18(1):57-71. Pubmed
  2. Quistad GB, Zhang N, Sparks SE, Casida JE: Phosphoacetylcholinesterase: toxicity of phosphorus oxychloride to mammals and insects that can be attributed to selective phosphorylation of acetylcholinesterase by phosphorodichloridic acid. Chem Res Toxicol. 2000 Jul;13(7):652-7. Pubmed
  3. da Costa VL Jr, Lapa AJ, Godinho RO: Short- and long-term influences of calcitonin gene-related peptide on the synthesis of acetylcholinesterase in mammalian myotubes. Br J Pharmacol. 2001 May;133(2):229-36. Pubmed
  4. Pang YP, Kollmeyer TM, Hong F, Lee JC, Hammond PI, Haugabouk SP, Brimijoin S: Rational design of alkylene-linked bis-pyridiniumaldoximes as improved acetylcholinesterase reactivators. Chem Biol. 2003 Jun;10(6):491-502. Pubmed
  5. Ashani Y, Gentry MK, Doctor BP: Differences in conformational stability between native and phosphorylated acetylcholinesterase as evidenced by a monoclonal antibody. Biochemistry. 1990 Mar 13;29(10):2456-63. Pubmed
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

2. Cholinesterase

Pharmacological action: yes
Actions: inhibitor

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

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

References:
  1. Kamata R, Saito S, Suzuki T, Takewaki T, Kobayashi H: Correlation of binding sites for diisopropyl phosphorofluoridate with cholinesterase and neuropathy target esterase in membrane and cytosol preparations from hen. Neurotoxicology. 2001 Apr;22(2):203-14. Pubmed
  2. Acey RA, Bailey S, Healy P, Jo C, Unger TF, Hudson RA: A butyrylcholinesterase in the early development of the brine shrimp (Artemia salina) larvae: a target for phthalate ester embryotoxicity? Biochem Biophys Res Commun. 2002 Dec 13;299(4):659-62. Pubmed
  3. Pittel Z, Cohen S, Fisher A, Heldman E: Differential long-term effect of AF64A on [3H]ACh synthesis and release in rat hippocampal synaptosomes. Brain Res. 1992 Jul 17;586(1):148-51. Pubmed
  4. Miller RB, Blank CL: Determination of serum cholinesterase activity by liquid chromatography with electrochemical detection. Anal Biochem. 1991 Aug 1;196(2):377-84. Pubmed
  5. Kelly SS, Ferry CB, Bamforth JP: The effects of anticholinesterases on the latencies of action potentials in mouse skeletal muscles. Br J Pharmacol. 1990 Apr;99(4):721-6. Pubmed
Enzymes

1. Cholinesterase

Actions: inhibitor

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. Kamata R, Saito S, Suzuki T, Takewaki T, Kobayashi H: Correlation of binding sites for diisopropyl phosphorofluoridate with cholinesterase and neuropathy target esterase in membrane and cytosol preparations from hen. Neurotoxicology. 2001 Apr;22(2):203-14. Pubmed
  2. Acey RA, Bailey S, Healy P, Jo C, Unger TF, Hudson RA: A butyrylcholinesterase in the early development of the brine shrimp (Artemia salina) larvae: a target for phthalate ester embryotoxicity? Biochem Biophys Res Commun. 2002 Dec 13;299(4):659-62. Pubmed
  3. Pittel Z, Cohen S, Fisher A, Heldman E: Differential long-term effect of AF64A on [3H]ACh synthesis and release in rat hippocampal synaptosomes. Brain Res. 1992 Jul 17;586(1):148-51. Pubmed
  4. Miller RB, Blank CL: Determination of serum cholinesterase activity by liquid chromatography with electrochemical detection. Anal Biochem. 1991 Aug 1;196(2):377-84. Pubmed
  5. Kelly SS, Ferry CB, Bamforth JP: The effects of anticholinesterases on the latencies of action potentials in mouse skeletal muscles. Br J Pharmacol. 1990 Apr;99(4):721-6. Pubmed
  6. Masson P, Fortier PL, Albaret C, Froment MT, Bartels CF, Lockridge O: Aging of di-isopropyl-phosphorylated human butyrylcholinesterase. Biochem J. 1997 Oct 15;327 ( Pt 2):601-7. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:19