Frovatriptan (CHEM002317)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesTargets (2)XML
Record Information
Version1.0
Creation Date2009-07-21 20:28:08 UTC
Update Date2026-03-27 01:52:43 UTC
Accession NumberCHEM002317
Identification
Common NameFrovatriptan
ClassSmall Molecule
DescriptionFrovatriptan (Frova™) is a triptan drug developed by Vernalis for the treatment of migraine headaches, in particular 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. Frovatriptan has mean terminal elimination half-life of approximately 26 hours, which is substantially longer than other triptans. Frovatriptan is available only by prescription in the United States, where a secondary New Drug Approval (sNDA) was filed in July 2006[2] and which is currently pending.[3] The FDA anticipates completing its review of this application on or before the current PDUFA (Prescription Drug User Fee Act) review date of August 19, 2007. If the sNDA is approved, Frova™ will be the only medication indicated in the U.S. for the short-term prevention of menstrual migraine (MM).
Contaminant Sources
  • HMDB Contaminants - Urine
  • STOFF IDENT Compounds
  • T3DB toxins
Contaminant Type
  • Amide
  • Amine
  • Anti-Inflammatory Agent
  • Anti-Migraine Agent
  • Drug
  • Ester
  • Metabolite
  • Organic Compound
  • Serotonin Agonist
  • Serotonin Receptor Agonist
  • Synthetic Compound
  • Vasoconstrictor Agent
Chemical Structure
Thumb
MOLSDFPDBSMILESInChI
Synonyms
ValueSource
Allergo filmtablettenKegg
Frovatriptan succinateHMDB
3-Methylamino-6-carboxamido-1,2,3,4-tetrahydrocarbazoleHMDB
FrovelanHMDB
VML-251HMDB
AllegroHMDB
FrovaHMDB
(+)-(R)-5,6,7,8-Tetrahydro-6-(methylamino)carbazole-3-carboxamide succinate (1:1), monohydrateHMDB
Chemical FormulaC14H17N3O
Average Molecular Mass243.304 g/mol
Monoisotopic Mass243.137 g/mol
CAS Registry Number158747-02-5
IUPAC Name(3R)-3-(methylamino)-2,3,4,9-tetrahydro-1H-carbazole-6-carboxamide
Traditional Namefrovatriptan
SMILESCN[C@@H]1CCC2=C(C1)C1=C(N2)C=CC(=C1)C(N)=O
InChI IdentifierInChI=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 KeyXPSQPHWEGNHMSK-SECBINFHSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as carbazoles. Carbazoles are compounds containing a three ring system containing a pyrrole ring fused on either side to a benzene ring.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassIndoles and derivatives
Sub ClassCarbazoles
Direct ParentCarbazoles
Alternative Parents
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
Molecular FrameworkAromatic heteropolycyclic compounds
External DescriptorsNot Available
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
ApplicationsNot Available
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting PointNot Available
Boiling PointNot Available
SolubilitySoluble
Predicted Properties
PropertyValueSource
Water Solubility0.12 g/LALOGPS
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 ŲChemAxon
Rotatable Bond Count2ChemAxon
Refractivity71.84 m³·mol⁻¹ChemAxon
Polarizability27.55 ųChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-004i-3690000000-20d2133e95fbc6b1f414Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot AvailableSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0006-0190000000-fc527e672048d9bf866cSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-004i-0490000000-09182e67659519af87e7Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0l1i-0910000000-81f4aa818323e96b5464Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0006-0090000000-bd79ad698f8bd9fbb84bSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0006-2490000000-4632cbf11a6dc353d2cfSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0006-9200000000-948170ac23122892a5adSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0006-0090000000-168fda82142bf345541bSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-002f-0090000000-3dac4efa84856ab16486Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-000i-0910000000-bdfabb283d321aa1d9e3Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0006-0090000000-932ee60351365d51e611Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0006-1190000000-c3fd5753f8f9a8a098ebSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0006-4910000000-8fac1192455fd2253b72Spectrum
Toxicity Profile
Route of ExposureFrovatriptan is rapidly absorbed from the duodenum, but has low oral bioavailability.
Mechanism of ToxicityThree distinct pharmacological actions have been implicated in the antimigraine effect of the triptans: (1) stimulation of presynaptic 5-HT1D receptors, which serves to inhibit both dural vasodilation and inflammation; (2) direct inhibition of trigeminal nuclei cell excitability via 5-HT1B/1D receptor agonism in the brainstem and (3) vasoconstriction of meningeal, dural, cerebral or pial vessels as a result of vascular 5-HT1B receptor agonism.
MetabolismIn vitro, cytochrome P450 1A2 appears to be the principal enzyme involved in the metabolism of frovatriptan to several metabolites including hydroxylated frovatriptan, N-acetyl desmethyl frovatriptan, hydroxylated N-acetyl desmethyl frovatriptan and desmethyl frovatriptan, and several other minor metabolites. Desmethyl frovatriptan has lower affinity for 5-HT1B/1D receptors compared to the parent compound. The N-acetyl desmethyl metabolite has no significant affinity for 5-HT receptors. The activity of the other metabolites is unknown. Route of Elimination: Radiolabeled compounds excreted in urine were unchanged frovatriptan, hydroxylated frovatriptan, N-acetyl desmethyl frovatriptan, hydroxylated N-acetyl desmethyl frovatriptan and desmethyl frovatriptan, together with several other minor metabolites. Less than 10% of frovatriptan was excreted in urine after an oral dose. Half Life: 26 hours
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesFor the acute treatment of migraine attacks with or without aura in adults.
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsThere is no direct experience of any patient taking an overdose of Frovatriptan. The maximum single dose of frovatriptan given to male and female patients with migraine was 40 mg (16 times the clinical dose) and the maximum single dose given to healthy male subjects was 100 mg (40 times the clinical dose) without significant adverse events.
TreatmentAs with other 5-HT1 receptor agonists, there is no specific antidote for frovatriptan. The elimination half-life of frovatriptan is 26 hours, therefore if overdose occurs, the patient should be monitored closely for at least 48 hours and be given any necessary symptomatic treatment. (8)
Concentrations
Not Available
DrugBank IDDB00998
HMDB IDHMDB0015133
FooDB IDNot Available
Phenol Explorer IDNot Available
KNApSAcK IDNot Available
BiGG IDNot Available
BioCyc IDNot Available
METLIN IDNot Available
PDB IDNot Available
Wikipedia LinkFrovatriptan
Chemspider ID70378
ChEBI ID350328
PubChem Compound ID77992
Kegg Compound IDNot Available
YMDB IDNot Available
ECMDB IDNot Available
References
Synthesis Reference

Samir Naik, Anthony Crasto, Narendra Joshi, Sachin Srivastava, “Amorphous frovatriptan succinate and process for the preparation thereof.” U.S. Patent US20070299123, issued December 27, 2007.

MSDSNot Available
General References
1. 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.
2. Easthope SE, Goa KL: Frovatriptan. CNS Drugs. 2001;15(12):969-76; discussion 977-8.
3. Balbisi EA: Frovatriptan succinate, a 5-HT1B/1D receptor agonist for migraine. Int J Clin Pract. 2004 Jul;58(7):695-705.
4. Elkind AH, Wade A, Ishkanian G: Pharmacokinetics of frovatriptan in adolescent migraineurs. J Clin Pharmacol. 2004 Oct;44(10):1158-65.
5. Markus F, Mikko K: Frovatriptan review. Expert Opin Pharmacother. 2007 Dec;8(17):3029-33.
6. 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.