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Frovatriptan

July 24, 2017
Common Name

Frovatriptan Description

Frovatriptan (Frova) is a triptan drug developed by Vernalis for the treatment of migraine headaches, in particliar those associated with menstruation. The product is licensed to Endo Pharmaceuticals in North America and Menarini in Europe.[1] Frovatriptan causes vasoconstriction of arteries and veins that supply blood to the head. It is available as 2.5 mg tablets. Structure

MOLSDF3D-SDFPDBSMILESInChI View 3D Structure

Synonyms

Value Source allergo FilmtablettenKegg Frovatriptan succinateHMDB 3-methylamino-6-carboxamido-1,2,3,4-TetrahydrocarbazoleMeSH FrovelanMeSH VML-251MeSH AllegroMeSH FrovaMeSH

Chemical Formlia

C14H17N3O Average Molecliar Weight

243.3043 Monoisotopic Molecliar Weight

243.137162181 IUPAC Name

(3R)-3-(methylamino)-2,3,4,9-tetrahydro-1H-carbazole-6-carboxamide Traditional Name

frovatriptan CAS Registry Number

158747-02-5 SMILES

CN[C@@H]1CCC2=C(C1)C1=C(N2)C=CC(=C1)C(N)=O

InChI Identifier

InChI=1S/C14H17N3O/c1-16-9-3-5-13-11(7-9)10-6-8(14(15)18)2-4-12(10)17-13/h2,4,6,9,16-17H,3,5,7H2,1H3,(H2,15,18)/t9-/m1/s1

InChI Key

XPSQPHWEGNHMSK-SECBINFHSA-N Chemical Taxonomy Description

This compound belongs to the class of chemical entities known as carbazoles. These are compounds containing a three ring system containing a pyrrole ring fused on either side to a benzene ring. Kingdom

Chemical entities Super Class

Organic compounds Class

Organoheterocyclic compounds Sub Class

Indoles and derivatives Direct Parent

Carbazoles Alternative Parents

  • Indolecarboxamides and derivatives
  • 3-alkylindoles
  • Aralkylamines
  • Benzenoids
  • Pyrroles
  • Heteroaromatic compounds
  • Primary carboxylic acid amides
  • Amino acids and derivatives
  • Dialkylamines
  • Azacyclic compounds
  • Organopnictogen compounds
  • Organooxygen compounds
  • Organic oxides
  • Hydrocarbon derivatives

    • Substituents

  • Carbazole
  • Indolecarboxamide derivative
  • Indolecarboxylic acid derivative
  • 3-alkylindole
  • Indole
  • Aralkylamine
  • Benzenoid
  • Heteroaromatic compound
  • Pyrrole
  • Amino acid or derivatives
  • Carboxamide group
  • Primary carboxylic acid amide
  • Carboxylic acid derivative
  • Secondary aliphatic amine
  • Azacycle
  • Secondary amine
  • Hydrocarbon derivative
  • Organic oxide
  • Organic nitrogen compound
  • Amine
  • Organopnictogen compound
  • Organonitrogen compound
  • Organooxygen compound
  • Organic oxygen compound
  • Aromatic heteropolycyclic compound

    • Molecliar Framework

    Aromatic heteropolycyclic compounds External Descriptors

    Not Available Ontology Status

    Expected but not Quantified Origin

  • Drug

    • Biofunction

  • Anti-inflammatory Agents
  • Anti-migraine Agents
  • Serotonin Agonists
  • Vasoconstrictor Agents

    • Application

  • Pharmaceutical

    • Cellliar locations

  • Membrane

    • Physical Properties State

    Solid Experimental Properties

    Property Value Reference Melting PointNot AvailableNot Available Boiling PointNot AvailableNot Available Water Solubility1.23e-01 g/LNot Available LogP0.9Not Available

    Predicted Properties

    Property Value Source Water Solubility0.12 mg/mLALOGPS logP1.2ALOGPS logP1.08ChemAxon logS-3.3ALOGPS pKa (Strongest Acidic)14.54ChemAxon pKa (Strongest Basic)10.42ChemAxon Physiological Charge1ChemAxon Hydrogen Acceptor Count2ChemAxon Hydrogen Donor Count3ChemAxon Polar Surface Area70.91 Å2ChemAxon Rotatable Bond Count2ChemAxon Refractivity71.84 m3·mol-1ChemAxon Polarizability27.55 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

  • Membrane

    • Biofluid Locations

  • Blood
  • Urine

    • Tissue Location

    Not Available Pathways

    Not Available Normal Concentrations

    Biofluid Status Value Age Sex Condition Reference Details BloodExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB00998

  • 21059682

    • details UrineExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB00998

  • 21059682

    • details

    Abnormal Concentrations

    Not Available Predicted Concentrations

    Biofluid Value Original age Original sex Original condition Comments Blood0-4 uMAdlit (>18 years old)BothNormalPredicted based on drug qualities Blood0-2 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

    DB00998 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

    70378 KEGG Compound ID

    Not Available BioCyc ID

    Not Available BiGG ID

    Not Available Wikipedia Link

    Frovatriptan NuGOwiki Link

    HMDB15133 Metagene Link

    HMDB15133 METLIN ID

    Not Available PubChem Compound

    77992 PDB ID

    Not Available ChEBI ID

    350328

    Product: CFTR(inh)-173

    References Synthesis Reference Not Available Material Safety Data Sheet (MSDS) Not Available General References
    1. Easthope SE, Goa KL: Frovatriptan. CNS Drugs. 2001;15(12):969-76; discussion 977-8. [PubMed:11735616 ]
    2. Balbisi EA: Frovatriptan succinate, a 5-HT1B/1D receptor agonist for migraine. Int J Clin Pract. 2004 Jul;58(7):695-705. [PubMed:15311727 ]
    3. Balbisi EA: Frovatriptan: a review of pharmacology, pharmacokinetics and clinical potential in the treatment of menstrual migraine. Ther Clin Risk Manag. 2006 Sep;2(3):303-8. [PubMed:18360605 ]
    4. Elkind AH, Wade A, Ishkanian G: Pharmacokinetics of frovatriptan in adolescent migraineurs. J Clin Pharmacol. 2004 Oct;44(10):1158-65. [PubMed:15342617 ]
    5. Markus F, Mikko K: Frovatriptan review. Expert Opin Pharmacother. 2007 Dec;8(17):3029-33. [PubMed:18001261 ]
    6. Jhee SS, Shiovitz T, Crawford AW, Cutler NR: Pharmacokinetics and pharmacodynamics of the triptan antimigraine agents: a comparative review. Clin Pharmacokinet. 2001;40(3):189-205. [PubMed:11327198 ]

    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 oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N3-demethylation. Also acts in the metabolism of aflatoxin B1 and acetaminophen. Participates in the bioactivation of carcinogenic aromatic and heterocyclic amines. Catalizes the N-hydroxylation of heterocyclic amines and the O-deethylation of phenacetin.
    Gene Name:
    CYP1A2
    Uniprot ID:
    P05177
    Molecular weight:
    58406.915
    References
    1. Easthope SE, Goa KL: Frovatriptan. CNS Drugs. 2001;15(12):969-76; discussion 977-8. [PubMed:11735616 ]
    2. Buchan P, Keywood C, Wade A, Ward C: Clinical pharmacokinetics of frovatriptan. Headache. 2002 Apr;42 Suppl 2:S54-62. [PubMed:12028321 ]
    3. Buchan P, Wade A, Ward C, Oliver SD, Stewart AJ, Freestone S: Frovatriptan: a review of drug-drug interactions. Headache. 2002 Apr;42 Suppl 2:S63-73. [PubMed:12028322 ]
    4. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
    General function:
    Involved in G-protein coupled receptor protein signaling pathway
    Specific function:
    This is one of the several different receptors for 5- hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. The activity of this receptor is mediated by G proteins that inhibit adenylate cyclase activity
    Gene Name:
    HTR1B
    Uniprot ID:
    P28222
    Molecular weight:
    43567.5
    References
    1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
    2. Balbisi EA: Frovatriptan succinate, a 5-HT1B/1D receptor agonist for migraine. Int J Clin Pract. 2004 Jul;58(7):695-705. [PubMed:15311727 ]
    3. Comer MB: Pharmacology of the selective 5-HT(1B/1D) agonist frovatriptan. Headache. 2002 Apr;42 Suppl 2:S47-53. [PubMed:12028320 ]
    4. Parsons AA, Raval P, Smith S, Tilford N, King FD, Kaumann AJ, Hunter J: Effects of the novel high-affinity 5-HT(1B/1D)-receptor ligand frovatriptan in human isolated basilar and coronary arteries. J Cardiovasc Pharmacol. 1998 Aug;32(2):220-4. [PubMed:9700983 ]
    5. Easthope SE, Goa KL: Frovatriptan. CNS Drugs. 2001;15(12):969-76; discussion 977-8. [PubMed:11735616 ]
    6. Dodick DW, Sandrini G, Williams P: Use of the sustained pain-free plus no adverse events endpoint in clinical trials of triptans in acute migraine. CNS Drugs. 2007;21(1):73-82. [PubMed:17190530 ]
    7. Tfelt-Hansen P, De Vries P, Saxena PR: Triptans in migraine: a comparative review of pharmacology, pharmacokinetics and efficacy. Drugs. 2000 Dec;60(6):1259-87. [PubMed:11152011 ]
    8. Deleu D, Hanssens Y: Current and emerging second-generation triptans in acute migraine therapy: a comparative review. J Clin Pharmacol. 2000 Jul;40(7):687-700. [PubMed:10883409 ]
    9. Markus F, Mikko K: Frovatriptan review. Expert Opin Pharmacother. 2007 Dec;8(17):3029-33. [PubMed:18001261 ]
    10. Balbisi EA: Frovatriptan: a review of pharmacology, pharmacokinetics and clinical potential in the treatment of menstrual migraine. Ther Clin Risk Manag. 2006 Sep;2(3):303-8. [PubMed:18360605 ]
    11. Elkind AH, Wade A, Ishkanian G: Pharmacokinetics of frovatriptan in adolescent migraineurs. J Clin Pharmacol. 2004 Oct;44(10):1158-65. [PubMed:15342617 ]
    12. Buchan P, Wade A, Ward C, Oliver SD, Stewart AJ, Freestone S: Frovatriptan: a review of drug-drug interactions. Headache. 2002 Apr;42 Suppl 2:S63-73. [PubMed:12028322 ]
    General function:
    Involved in G-protein coupled receptor protein signaling pathway
    Specific function:
    This is one of the several different receptors for 5- hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. The activity of this receptor is mediated by G proteins that inhibit adenylate cyclase activity
    Gene Name:
    HTR1D
    Uniprot ID:
    P28221
    Molecular weight:
    41906.4
    References
    1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
    2. Easthope SE, Goa KL: Frovatriptan. CNS Drugs. 2001;15(12):969-76; discussion 977-8. [PubMed:11735616 ]
    3. Comer MB: Pharmacology of the selective 5-HT(1B/1D) agonist frovatriptan. Headache. 2002 Apr;42 Suppl 2:S47-53. [PubMed:12028320 ]
    4. Tfelt-Hansen P, De Vries P, Saxena PR: Triptans in migraine: a comparative review of pharmacology, pharmacokinetics and efficacy. Drugs. 2000 Dec;60(6):1259-87. [PubMed:11152011 ]
    5. Deleu D, Hanssens Y: Current and emerging second-generation triptans in acute migraine therapy: a comparative review. J Clin Pharmacol. 2000 Jul;40(7):687-700. [PubMed:10883409 ]
    6. Jahnichen S, Radtke OA, Pertz HH: Involvement of 5-HT1B receptors in triptan-induced contractile responses in guinea-pig isolated iliac artery. Naunyn Schmiedebergs Arch Pharmacol. 2004 Jul;370(1):54-63. Epub 2004 Jun 8. [PubMed:15185063 ]
    7. Balbisi EA: Frovatriptan succinate, a 5-HT1B/1D receptor agonist for migraine. Int J Clin Pract. 2004 Jul;58(7):695-705. [PubMed:15311727 ]
    8. Parsons AA, Raval P, Smith S, Tilford N, King FD, Kaumann AJ, Hunter J: Effects of the novel high-affinity 5-HT(1B/1D)-receptor ligand frovatriptan in human isolated basilar and coronary arteries. J Cardiovasc Pharmacol. 1998 Aug;32(2):220-4. [PubMed:9700983 ]
    9. Balbisi EA: Frovatriptan: a review of pharmacology, pharmacokinetics and clinical potential in the treatment of menstrual migraine. Ther Clin Risk Manag. 2006 Sep;2(3):303-8. [PubMed:18360605 ]
    10. Elkind AH, Wade A, Ishkanian G: Pharmacokinetics of frovatriptan in adolescent migraineurs. J Clin Pharmacol. 2004 Oct;44(10):1158-65. [PubMed:15342617 ]
    11. Buchan P, Wade A, Ward C, Oliver SD, Stewart AJ, Freestone S: Frovatriptan: a review of drug-drug interactions. Headache. 2002 Apr;42 Suppl 2:S63-73. [PubMed:12028322 ]

    PMID: 8521497

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