Record Information |
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Version | 2.0 |
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Creation Date | 2009-07-21 20:28:46 UTC |
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Update Date | 2014-12-24 20:25:56 UTC |
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Accession Number | T3D3036 |
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Identification |
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Common Name | Fosphenytoin |
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Class | Small Molecule |
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Description | Fosphenytoin is a water-soluble phenytoin prodrug used only in hospitals for the treatment of epileptic seizures. It works by slowing down impulses in the brain that cause seizures. Its main mechanism is to block frequency-dependent, use-dependent and voltage-dependent neuronal sodium channels, and therefore limit repetitive firing of action potentials. |
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Compound Type | - Amide
- Amine
- Anticonvulsant
- Drug
- Metabolite
- Organic Compound
- Synthetic Compound
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Chemical Structure | |
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Synonyms | Synonym | (3-Phosphoryloxymethyl)phenytoin | Cerebyx | Fosfenitoina | Fosphenytoine | Fosphenytoinum | Prodilantin |
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Chemical Formula | C16H15N2O6P |
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Average Molecular Mass | 362.274 g/mol |
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Monoisotopic Mass | 362.067 g/mol |
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CAS Registry Number | 93390-81-9 |
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IUPAC Name | [(2,5-dioxo-4,4-diphenylimidazolidin-1-yl)methoxy]phosphonic acid |
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Traditional Name | fosphenytoin |
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SMILES | OC1=NC(C(=O)N1COP(O)(O)=O)(C1=CC=CC=C1)C1=CC=CC=C1 |
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InChI Identifier | InChI=1S/C16H15N2O6P/c19-14-16(12-7-3-1-4-8-12,13-9-5-2-6-10-13)17-15(20)18(14)11-24-25(21,22)23/h1-10H,11H2,(H,17,20)(H2,21,22,23) |
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InChI Key | InChIKey=XWLUWCNOOVRFPX-UHFFFAOYSA-N |
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Chemical Taxonomy |
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Description | belongs to the class of organic compounds known as diphenylmethanes. Diphenylmethanes are compounds containing a diphenylmethane moiety, which consists of a methane wherein two hydrogen atoms are replaced by two phenyl groups. |
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Kingdom | Organic compounds |
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Super Class | Benzenoids |
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Class | Benzene and substituted derivatives |
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Sub Class | Diphenylmethanes |
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Direct Parent | Diphenylmethanes |
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Alternative Parents | |
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Substituents | - Diphenylmethane
- Alpha-amino acid or derivatives
- N-acyl urea
- Ureide
- Monoalkyl phosphate
- Imidazolinone
- Organic phosphoric acid derivative
- Phosphoric acid ester
- Alkyl phosphate
- 2-imidazoline
- Isourea
- Azacycle
- Carboxylic acid derivative
- Carboximidamide
- Organoheterocyclic compound
- Organic 1,3-dipolar compound
- Propargyl-type 1,3-dipolar organic compound
- Hydrocarbon derivative
- Organopnictogen compound
- Organic nitrogen compound
- Organonitrogen compound
- Organic oxygen compound
- Organooxygen compound
- Carbonyl group
- Organic oxide
- Aromatic heteromonocyclic compound
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Molecular Framework | Aromatic heteromonocyclic compounds |
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External Descriptors | |
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Biological Properties |
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Status | Detected and Not Quantified |
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Origin | Exogenous |
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Cellular Locations | |
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Biofluid Locations | Not Available |
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Tissue Locations | Not Available |
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Pathways | Name | SMPDB Link | KEGG Link |
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Fosphenytoin (Antiarrhythmic) Pathway | Not Available | Not Available |
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Applications | Not Available |
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Biological Roles | Not Available |
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Chemical Roles | Not Available |
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Physical Properties |
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State | Solid |
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Appearance | White powder. |
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Experimental Properties | Property | Value |
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Melting Point | v . d . e Anticonvulsants ( N03 ) | Boiling Point | Not Available | Solubility | 1.45e-01 g/L | LogP | Not Available |
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Predicted Properties | |
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Spectra |
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Spectra | Spectrum Type | Description | Splash Key | Deposition Date | View |
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Predicted GC-MS | Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive | splash10-00ls-4941000000-7f020f5c4237af5bfb3c | 2017-09-01 | View Spectrum | Predicted GC-MS | Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive | Not Available | 2021-10-12 | View Spectrum | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 10V, Negative | splash10-03di-2009000000-f100b603f8bec4297f64 | 2016-08-03 | View Spectrum | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 20V, Negative | splash10-004i-9100000000-974b8eaa512f665645c7 | 2016-08-03 | View Spectrum | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 40V, Negative | splash10-002f-9000000000-edcf929c72670ddaeafe | 2016-08-03 | View Spectrum | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 10V, Negative | splash10-03di-0009000000-cc4d0db2ee88412c5f88 | 2021-10-11 | View Spectrum | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 20V, Negative | splash10-0udi-0944000000-f5c9d9bf3cb087cf7685 | 2021-10-11 | View Spectrum | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 40V, Negative | splash10-00p0-5930000000-1c6b6a79ed38b9c1414a | 2021-10-11 | View Spectrum | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 10V, Positive | splash10-03di-0019000000-801dc353a42886feac15 | 2016-06-03 | View Spectrum | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 20V, Positive | splash10-03dj-1019000000-954988a4832c09ddde71 | 2016-06-03 | View Spectrum | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 40V, Positive | splash10-0uy0-5931000000-a2e668ce8b6003249e52 | 2016-06-03 | View Spectrum | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 10V, Positive | splash10-03di-0029000000-80555bf6b08b1edde5ba | 2021-10-11 | View Spectrum | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 20V, Positive | splash10-014i-0191000000-7ba4d52b46cd24385200 | 2021-10-11 | View Spectrum | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 40V, Positive | splash10-0159-0920000000-be8b0958365f6e0346ab | 2021-10-11 | View Spectrum |
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Toxicity Profile |
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Route of Exposure | Fosphenytoin is completely bioavailable following lM administration. |
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Mechanism of Toxicity | Fosphenytoin is a prodrug of phenytoin and accordingly, its anticonvulsant effects are attributable to phenytoin. Phenytoin acts on sodium channels on the neuronal cell membrane, limiting the spread of seizure activity and reducing seizure propagation. By promoting sodium efflux from neurons, phenytoin tends to stabilize the threshold against hyperexcitability caused by excessive stimulation or environmental changes capable of reducing membrane sodium gradient. This includes the reduction of post-tetanic potentiation at synapses. Loss of post-tetanic potentiation prevents cortical seizure foci from detonating adjacent cortical areas. |
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Metabolism | Hepatic.
Route of Elimination: Phenytoin derived from administration of Cerebyx is extensively metabolized in the liver and excreted in urine primarily as 5-(p-hydroxyphenyl)-5-phenylhydantoin and its glucuronide; little unchanged phenytoin (1%-5% of the Cerebyx dose) is recovered in urine.
Half Life: Fosphenytoin has a half-life of approximately 15 minutes. |
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Toxicity Values | LD50: 156 mg PE/kg (Intravenous, Mouse) (4)
LD50: 250 mg PE/kg (Intravenous, Rat) (4) |
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Lethal Dose | Not Available |
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Carcinogenicity (IARC Classification) | No indication of carcinogenicity to humans (not listed by IARC). |
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Uses/Sources | For the control of generalized convulsive status epilepticus and prevention and treatment of seizures occurring during neurosurgery. It can also be substituted, short-term, for oral phenytoin. |
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Minimum Risk Level | Not Available |
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Health Effects | May cause a potentially dangerous rash that may develop into Stevens Johnson syndrome, an extremely rare but potentially fatal skin disease. |
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Symptoms | Nausea, vomiting, lethargy, tachycardia, bradycardia, asystole, cardiac arrest, hypotension, syncope, hypocalcemia, metabolic acidosis, and death have been reported in cases of overdosage with fosphenytoin. Signs of acute toxicity in animals included ataxia, labored breathing, ptosis, and hypoactivity. |
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Treatment | Treatment is nonspecific since there is no known antidote to Fosphenytoin overdosage. The adequacy of the respiratory and circulatory systems should be carefully observed, and appropriate supportive measures employed. Hemodialysis can be considered since phenytoin is not completely bound to plasma proteins. Total exchange transfusion has been used in the treatment of severe intoxication in children. (7) |
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Normal Concentrations |
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| Not Available |
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Abnormal Concentrations |
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| Not Available |
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External Links |
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DrugBank ID | DB01320 |
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HMDB ID | HMDB15417 |
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PubChem Compound ID | 56339 |
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ChEMBL ID | CHEMBL1201336 |
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ChemSpider ID | 50839 |
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KEGG ID | C07840 |
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UniProt ID | Not Available |
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OMIM ID | |
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ChEBI ID | 775287 |
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BioCyc ID | Not Available |
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CTD ID | Not Available |
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Stitch ID | Fosphenytoin |
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PDB ID | Not Available |
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ACToR ID | Not Available |
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Wikipedia Link | Fosphenytoin |
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References |
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Synthesis Reference | Volker Kirsch, “Process for the preparation of sodium fosphenytoin.” U.S. Patent US20050272706, issued December 08, 2005. |
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MSDS | T3D3036.pdf |
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General References | - Johnson J, Wrenn K: Inappropriate fosphenytoin use in the ED. Am J Emerg Med. 2001 Jul;19(4):293-4. [11447516 ]
- Applebaum J, Levine J, Belmaker RH: Intravenous fosphenytoin in acute mania. J Clin Psychiatry. 2003 Apr;64(4):408-9. [12716241 ]
- McCleane GJ: Intravenous infusion of fosphenytoin produces prolonged pain relief: a case report. J Pain. 2002 Apr;3(2):156-8. [14622802 ]
- Wishart DS, Knox C, Guo AC, Cheng D, Shrivastava S, Tzur D, Gautam B, Hassanali M: DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6. Epub 2007 Nov 29. [18048412 ]
- Luszczki JJ: Third-generation antiepileptic drugs: mechanisms of action, pharmacokinetics and interactions. Pharmacol Rep. 2009 Mar-Apr;61(2):197-216. [19443931 ]
- Browne TR, Kugler AR, Eldon MA: Pharmacology and pharmacokinetics of fosphenytoin. Neurology. 1996 Jun;46(6 Suppl 1):S3-7. [8649612 ]
- RxList: The Internet Drug Index (2009). [Link]
- Gaval-Cruz M, Weinshenker D: mechanisms of disulfiram-induced cocaine abstinence: antabuse and cocaine relapse. Mol Interv. 2009 Aug;9(4):175-87. [Link]
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Gene Regulation |
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Up-Regulated Genes | Not Available |
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Down-Regulated Genes | Not Available |
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