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

• ChemBase ID: 871
• Molecular Formular: C14H17N3O
• Molecular Mass: 243.30428
• Monoisotopic Mass: 243.13716218
• SMILES: O=C(N)c1cc2c3C[C@H](NC)CCc3[nH]c2cc1
• Canonical SMILES: CN[C@H]1Cc2c(CC1)[nH]c1c2cc(cc1)C(=O)N
• InChI: 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
• InChIKey: XPSQPHWEGNHMSK-SECBINFHSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: (3R)-3-(methylamino)-2,3,4,9-tetrahydro-1H-carbazole-6-carboxamide
• IUPAC Traditional name: frovatriptan
• Brand Name: Miguard; Frova; Frovelan
• Synonyms: Frovatriptan succinate; frovatriptan; Frovatriptan

Database IDs

• CAS Number: 158747-02-5
• PubChem SID: 160964334; 46506288
• PubChem CID: 77992

CALCULATED PROPERTIES

JChem

• Acid pKa: 14.536194
• H Acceptors: 2
• H Donor: 3
• LogD (pH = 5.5): -2.1550536
• LogD (pH = 7.4): -1.739132
• Log P: 1.077976
• Molar Refractivity: 71.8382 cm^3
• Polarizability: 28.223196 Å^3
• Polar Surface Area: 70.91 Å^2
• Rotatable Bonds: 2
• Lipinski's Rule of Five: true

ALOGPS 2.1

• Log P: 1.2
• LOG S: -3.3
• Solubility (Water): 1.23e-01 g/l

PROPERTIES

Physical Property

• Solubility: Soluble
• Hydrophobicity(logP): 0.9

DETAILS

DrugBank - DB00998

• Drug Groups: approved; investigational
• Description: Frovatriptan (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).
• Indication: For the acute treatment of migraine attacks with or without aura in adults.
• Pharmacology: Frovatriptan is a second generation triptan 5-HT receptor agonist that binds with high affinity for 5-HT_1B and 5-HT_1D receptors. It is structurally distinct from, but pharmacologically related to other selective 5-HT_1B/1D receptor agonists. Frovatriptan has no significant effects on GABA_A mediated channel activity and has no significant affinity for benzodiazepine binding sites. Frovatriptan is believed to act on extracerebral, intracranial arteries and to inhibit excessive dilation of these vessels in migraine. Research has shown that migraine can be caused by the swelling of blood vessels around the brain. Frovatriptan eases the pain associated with migraine by narrowing these blood vessels. Frovatriptan has one of the highest affinities for the 5-HT_1B of the second-generation triptan agonists.
• Toxicity: There 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.
• Affected Organisms: Humans and other mammals
• Biotransformation: In 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-HT_1B/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.
• Absorption: Frovatriptan is rapidly absorbed from the duodenum, but has low oral bioavailability.
• Half Life: 26 hours
• Protein Binding: Binding to serum proteins is low (approximately 15%). Reversible binding to blood cells at equilibrium is approximately 60%.
• 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.
• Distribution: * 4.2 L/kg [males]; * 3 L/kg [females]
• Clearance: * 220 mL/min [male receiving IV dose of 0.8 mg]; * 130 mL/min [Female receiving IV dose of 0.8 mg]
• References: Markus F, Mikko K: Frovatriptan review. Expert Opin Pharmacother. 2007 Dec;8(17):3029-33. [Pubmed] ; Easthope SE, Goa KL: Frovatriptan. CNS Drugs. 2001;15(12):969-76; discussion 977-8. [Pubmed] ; 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] ; Balbisi EA: Frovatriptan succinate, a 5-HT1B/1D receptor agonist for migraine. Int J Clin Pract. 2004 Jul;58(7):695-705. [Pubmed] ; Elkind AH, Wade A, Ishkanian G: Pharmacokinetics of frovatriptan in adolescent migraineurs. J Clin Pharmacol. 2004 Oct;44(10):1158-65. [Pubmed] ; 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]
• External Links: Wikipedia; RxList; PDRhealth; Drugs.com

REFERENCES

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