Posted inUncategorized

Fosphenytoin

July 24, 2017
Common Name

Fosphenytoin Description

Fosphenytoin is a water-soluble phenytoin prodrug used only in hospitals for the treatment of epileptic seizures. It works by slowing down implises 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. Structure

MOLSDF3D-SDFPDBSMILESInChI View 3D Structure

Synonyms

Value Source (3-Phosphoryloxymethyl)phenytoinHMDB CerebyxMeSH HMPDPMeSH 3-(Hydroxymethyl)phenytoin disodium phosphateMeSH Fosphenytoin, disodium saltMeSH ProdilantinMeSH Fosphenytoin sodiumMeSH 3-(Hydroxymethyl)phenytoin phosphate esterMeSH

Chemical Formlia

C16H15N2O6P Average Molecliar Weight

362.2739 Monoisotopic Molecliar Weight

362.066772734 IUPAC Name

[(2,5-dioxo-4,4-diphenylimidazolidin-1-yl)methoxy]phosphonic acid Traditional Name

fosphenytoin CAS Registry Number

93390-81-9 SMILES

OP(O)(=O)OCN1C(=O)NC(C1=O)(C1=CC=CC=C1)C1=CC=CC=C1

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)

InChI Key

XWLUWCNOOVRFPX-UHFFFAOYSA-N Chemical Taxonomy Description

This compound belongs to the class of chemical entities known as diphenylmethanes. These are compounds containing a diphenylmethane moiety, which consists of a methane wherein two hydrogen atoms are replaced by two phenyl groups. Kingdom

Chemical entities Super Class

Organic compounds Class

Benzenoids Sub Class

Benzene and substituted derivatives Direct Parent

Diphenylmethanes Alternative Parents

  • Alpha amino acids and derivatives
  • Ureides
  • Monoalkyl phosphates
  • Imidazolinones
  • Isoureas
  • Propargyl-type 1,3-dipolar organic compounds
  • Carboximidamides
  • Azacyclic compounds
  • Organopnictogen compounds
  • Organic oxides
  • Hydrocarbon derivatives
  • Carbonyl compounds

    • Substituents

  • Diphenylmethane
  • Alpha-amino acid or derivatives
  • Ureide
  • Monoalkyl phosphate
  • Imidazolinone
  • Organic phosphoric acid derivative
  • Phosphoric acid ester
  • Alkyl phosphate
  • 2-imidazoline
  • Isourea
  • Propargyl-type 1,3-dipolar organic compound
  • Azacycle
  • Carboxylic acid derivative
  • Carboximidamide
  • Organoheterocyclic compound
  • Organic 1,3-dipolar compound
  • Hydrocarbon derivative
  • Organonitrogen compound
  • Organic nitrogen compound
  • Organooxygen compound
  • Organic oxygen compound
  • Carbonyl group
  • Organopnictogen compound
  • Organic oxide
  • Aromatic heteromonocyclic compound

    • Molecliar Framework

    Aromatic heteromonocyclic compounds External Descriptors

  • imidazolidine-2,4-dione (CHEBI:5165 )

    • Ontology Status

    Expected but not Quantified Origin

  • Drug

    • Biofunction

  • Anticonvlisants

    • Application

  • Pharmaceutical

    • Cellliar locations

  • Extracellliar
  • Membrane

    • Physical Properties State

    Solid Experimental Properties

    Property Value Reference Melting PointNot AvailableNot Available Boiling PointNot AvailableNot Available Water Solubility1.45e-01 g/LNot Available LogPNot AvailableNot Available

    Predicted Properties

    Property Value Source Water Solubility0.14 mg/mLALOGPS logP1.08ALOGPS logP1.67ChemAxon logS-3.4ALOGPS pKa (Strongest Acidic)1.46ChemAxon pKa (Strongest Basic)-9.7ChemAxon Physiological Charge-2ChemAxon Hydrogen Acceptor Count5ChemAxon Hydrogen Donor Count3ChemAxon Polar Surface Area116.17 Å2ChemAxon Rotatable Bond Count5ChemAxon Refractivity87.05 m3·mol-1ChemAxon Polarizability33.23 Å3ChemAxon Number of Rings3ChemAxon Bioavailability1ChemAxon Rlie of FiveYesChemAxon Ghose FilterYesChemAxon Vebers RlieYesChemAxon MDDR-like RlieYesChemAxon

    Spectra Spectra

    Spectrum Type Description Splash Key Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 10V, PositiveNot Available Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 20V, PositiveNot Available Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 40V, PositiveNot Available Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 10V, NegativeNot Available Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 20V, NegativeNot Available Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 40V, NegativeNot Available

    Biological Properties Cellliar Locations

  • Extracellliar
  • Membrane

    • Biofluid Locations

  • Blood
  • Urine

    • Tissue Location

    Not Available Pathways

    Name SMPDB Link KEGG Link Fosphenytoin (Antiarrhythmic) Metabolism PathwaySMP00618Not Available Fosphenytoin (Antiarrhythmic) PathwaySMP00326Not Available

    Normal Concentrations

    Biofluid Status Value Age Sex Condition Reference Details BloodExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB01320

  • 21059682

    • details UrineExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB01320

  • 21059682

    • details

    Abnormal Concentrations

    Not Available Predicted Concentrations

    Biofluid Value Original age Original sex Original condition Comments Blood0-3 uMAdlit (>18 years old)BothNormalPredicted based on drug qualities Blood0-1 umol/mmol creatinineAdlit (>18 years old)BothNormalPredicted based on drug qualities

    Associated Disorders and Diseases Disease References

    None Associated OMIM IDs

    None External Links DrugBank ID

    DB01320 DrugBank Metabolite ID

    Not Available Phenol Explorer Compound ID

    Not Available Phenol Explorer Metabolite ID

    Not Available FoodDB ID

    Not Available KNApSAcK ID

    Not Available Chemspider ID

    50839 KEGG Compound ID

    C07840 BioCyc ID

    Not Available BiGG ID

    Not Available Wikipedia Link

    Fosphenytoin NuGOwiki Link

    HMDB15417 Metagene Link

    HMDB15417 METLIN ID

    Not Available PubChem Compound

    56339 PDB ID

    Not Available ChEBI ID

    775287

    Product: Rabeprazole

    References Synthesis Reference Not Available Material Safety Data Sheet (MSDS) Not Available General References
    1. Browne TR, Kugler AR, Eldon MA: Pharmacology and pharmacokinetics of fosphenytoin. Neurology. 1996 Jun;46(6 Suppl 1):S3-7. [PubMed:8649612 ]
    2. Johnson J, Wrenn K: Inappropriate fosphenytoin use in the ED. Am J Emerg Med. 2001 Jul;19(4):293-4. [PubMed:11447516 ]
    3. Applebaum J, Levine J, Belmaker RH: Intravenous fosphenytoin in acute mania. J Clin Psychiatry. 2003 Apr;64(4):408-9. [PubMed:12716241 ]
    4. McCleane GJ: Intravenous infusion of fosphenytoin produces prolonged pain relief: a case report. J Pain. 2002 Apr;3(2):156-8. [PubMed:14622802 ]
    5. Luszczki JJ: Third-generation antiepileptic drugs: mechanisms of action, pharmacokinetics and interactions. Pharmacol Rep. 2009 Mar-Apr;61(2):197-216. [PubMed:19443931 ]

    Enzymes

    General function:
    Involved in monooxygenase activity
    Specific function:
    Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,8-cineole 2-exo-monooxygenase. The enzyme also hydroxylates etoposide.
    Gene Name:
    CYP3A4
    Uniprot ID:
    P08684
    Molecular weight:
    57255.585
    References
    1. Zhou SF: Drugs behave as substrates, inhibitors and inducers of human cytochrome P450 3A4. Curr Drug Metab. 2008 May;9(4):310-22. [PubMed:18473749 ]
    General function:
    Involved in monooxygenase activity
    Specific function:
    Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenytoin, tolbutamide and losartan.
    Gene Name:
    CYP2C9
    Uniprot ID:
    P11712
    Molecular weight:
    55627.365
    References
    1. Sahi J, Shord SS, Lindley C, Ferguson S, LeCluyse EL: Regulation of cytochrome P450 2C9 expression in primary cultures of human hepatocytes. J Biochem Mol Toxicol. 2009 Jan-Feb;23(1):43-58. doi: 10.1002/jbt.20264. [PubMed:19202563 ]
    2. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [PubMed:19515014 ]
    3. Goldstein JA: Clinical relevance of genetic polymorphisms in the human CYP2C subfamily. Br J Clin Pharmacol. 2001 Oct;52(4):349-55. [PubMed:11678778 ]
    4. Klotz U: The role of pharmacogenetics in the metabolism of antiepileptic drugs: pharmacokinetic and therapeutic implications. Clin Pharmacokinet. 2007;46(4):271-9. [PubMed:17375979 ]
    General function:
    Involved in monooxygenase activity
    Specific function:
    Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and imipramine.
    Gene Name:
    CYP2C19
    Uniprot ID:
    P33261
    Molecular weight:
    55944.565
    References
    1. Anderson GD: Pharmacokinetic, pharmacodynamic, and pharmacogenetic targeted therapy of antiepileptic drugs. Ther Drug Monit. 2008 Apr;30(2):173-80. doi: 10.1097/FTD.0b013e318167d11b. [PubMed:18367977 ]
    2. Hennessy S, Leonard CE, Freeman CP, Metlay JP, Chu X, Strom BL, Bilker WB: CYP2C9, CYP2C19, and ABCB1 genotype and hospitalization for phenytoin toxicity. J Clin Pharmacol. 2009 Dec;49(12):1483-7. doi: 10.1177/0091270009343006. Epub 2009 Jul 17. [PubMed:19617466 ]
    3. Klotz U: The role of pharmacogenetics in the metabolism of antiepileptic drugs: pharmacokinetic and therapeutic implications. Clin Pharmacokinet. 2007;46(4):271-9. [PubMed:17375979 ]
    General function:
    Involved in monooxygenase activity
    Specific function:
    Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,4-cineole 2-exo-monooxygenase.
    Gene Name:
    CYP2B6
    Uniprot ID:
    P20813
    Molecular weight:
    56277.81
    References
    1. Wang H, Faucette S, Moore R, Sueyoshi T, Negishi M, LeCluyse E: Human constitutive androstane receptor mediates induction of CYP2B6 gene expression by phenytoin. J Biol Chem. 2004 Jul 9;279(28):29295-301. Epub 2004 Apr 28. [PubMed:15123723 ]
    2. Faucette SR, Wang H, Hamilton GA, Jolley SL, Gilbert D, Lindley C, Yan B, Negishi M, LeCluyse EL: Regulation of CYP2B6 in primary human hepatocytes by prototypical inducers. Drug Metab Dispos. 2004 Mar;32(3):348-58. [PubMed:14977870 ]
    General function:
    Involved in monooxygenase activity
    Specific function:
    Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. In the epoxidation of arachidonic acid it generates only 14,15- and 11,12-cis-epoxyeicosatrienoic acids. It is the principal enzyme responsible for the metabolism the anti-cancer drug paclitaxel (taxol).
    Gene Name:
    CYP2C8
    Uniprot ID:
    P10632
    Molecular weight:
    55824.275
    References
    1. Kim KA, Park JY: Inhibitory effect of glyburide on human cytochrome p450 isoforms in human liver microsomes. Drug Metab Dispos. 2003 Sep;31(9):1090-2. [PubMed:12920163 ]
    General function:
    Involved in ion channel activity
    Specific function:
    This protein mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient. It is a tetrodotoxin-resistant Na(+) channel isoform. This channel is responsible for the initial upstroke of the action potential in the electrocardiogram
    Gene Name:
    SCN5A
    Uniprot ID:
    Q14524
    Molecular weight:
    226937.5
    References
    1. Swadron SP, Rudis MI, Azimian K, Beringer P, Fort D, Orlinsky M: A comparison of phenytoin-loading techniques in the emergency department. Acad Emerg Med. 2004 Mar;11(3):244-52. [PubMed:15001403 ]
    2. Mantegazza M, Curia G, Biagini G, Ragsdale DS, Avoli M: Voltage-gated sodium channels as therapeutic targets in epilepsy and other neurological disorders. Lancet Neurol. 2010 Apr;9(4):413-24. doi: 10.1016/S1474-4422(10)70059-4. [PubMed:20298965 ]
    3. Lenkowski PW, Ko SH, Anderson JD, Brown ML, Patel MK: Block of human NaV1.5 sodium channels by novel alpha-hydroxyphenylamide analogues of phenytoin. Eur J Pharm Sci. 2004 Apr;21(5):635-44. [PubMed:15066664 ]
    4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]

    PMID: 25319116

    Last updated on