Tìm theo
Frovatriptan
Các tên gọi khác (2) :
  • Allergo filmtabletten
  • Frovatriptan succinate
serotonin receptor agonists, anti migraine agents
Thuốc Gốc
Small Molecule
CAS: 158747-02-5
ATC: N02CC07
ĐG : DispenseXpress Inc.
CTHH: C14H17N3O
PTK: 243.3043
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).
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C14H17N3O
Phân tử khối
243.3043
Monoisotopic mass
243.137162181
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
InChI Key
InChIKey=XPSQPHWEGNHMSK-SECBINFHSA-N
IUPAC Name
(3R)-3-(methylamino)-2,3,4,9-tetrahydro-1H-carbazole-6-carboxamide
Traditional IUPAC Name
frovatriptan
SMILES
CN[C@@H]1CCC2=C(C1)C1=C(N2)C=CC(=C1)C(N)=O
Độ hòa tan
Soluble
logP
0.9
logS
-3.3
pKa (strongest acidic)
14.54
pKa (Strongest Basic)
10.42
PSA
70.91 Å2
Refractivity
71.84 m3·mol-1
Polarizability
27.55 Å3
Rotatable Bond Count
2
H Bond Acceptor Count
2
H Bond Donor Count
3
Physiological Charge
1
Number of Rings
3
Bioavailability
1
Rule of Five
true
Ghose Filter
true
Dược Lực Học : Frovatriptan is a second generation triptan 5-HT receptor agonist that binds with high affinity for 5-HT1B and 5-HT1D receptors. It is structurally distinct from, but pharmacologically related to other selective 5-HT1B/1D receptor agonists. Frovatriptan has no significant effects on GABAA 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-HT1B of the second-generation triptan agonists.
Cơ Chế Tác Dụng : 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). Three 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.
Dược Động Học :
▧ Absorption :
Frovatriptan is rapidly absorbed from the duodenum, but has low oral bioavailability.
▧ Volume of Distribution :
* 4.2 L/kg [males] * 3 L/kg [females]
▧ Protein binding :
Binding to serum proteins is low (approximately 15%). Reversible binding to blood cells at equilibrium is approximately 60%.
▧ Metabolism :
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-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
▧ Clearance :
* 220 mL/min [male receiving IV dose of 0.8 mg] * 130 mL/min [Female receiving IV dose of 0.8 mg]
Độc Tính : 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.
Chỉ Định : For the acute treatment of migraine attacks with or without aura in adults.
Tương Tác Thuốc :
  • Citalopram Increased risk of CNS adverse effects
  • Desvenlafaxine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
  • Dihydroergotamine Possible severe and prolonged vasoconstriction
  • Ergonovine Possible severe and prolonged vasoconstriction
  • Ergotamine Possible severe and prolonged vasoconstriction
  • Escitalopram Increased risk of CNS adverse effects
  • Fluoxetine Increased risk of CNS adverse effects
  • Fluvoxamine Increased risk of CNS adverse effects
  • Methylergometrine Possible severe and prolonged vasoconstriction
  • Methysergide Possible severe and prolonged vasoconstriction
  • Nefazodone Increased risk of CNS adverse effects
  • Paroxetine Increased risk of CNS adverse effects
  • Sertraline Increased risk of CNS adverse effects
  • Sibutramine Increased risk of CNS adverse effects
  • Tramadol Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
  • Tranylcypromine Increased risk of serotonin syndrome. Use caution during concomitant therapy and monitor for symptoms of serotonin syndrome.
  • Trazodone Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
  • Trimipramine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
  • Venlafaxine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
  • Zolmitriptan Concomitant use of two serotonin 5-HT1D receptor agonists, such as zolmitriptan and frovatriptan, may result in additive vasoconstrictive effects. Concomitant use within 24 hours is contraindicated.
Liều Lượng & Cách Dùng : Tablet - Oral
Dữ Kiện Thương Mại
Giá thị trường
Nhà Sản Xuất
  • Công ty :
    Sản phẩm biệt dược : Frova
  • Công ty :
    Sản phẩm biệt dược : Frovelan
  • Công ty :
    Sản phẩm biệt dược : Miguard
Đóng gói
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB00998
PubChem Compound
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=77992
PubChem Substance
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=46506288
ChemSpider
http://www.chemspider.com/Chemical-Structure.70378.html
BindingDB
http://www.bindingdb.org/bind/chemsearch/marvin/MolStructure.jsp?monomerid=50073689
National Drug Code Directory
http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/63481-025-09
PharmGKB
http://www.pharmgkb.org/drug/PA164754891
Wikipedia
http://en.wikipedia.org/wiki/Frovatriptan
RxList
http://www.rxlist.com/cgi/generic3/frova.htm
PDRhealth
http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/fro1622.shtml
Drugs.com
http://www.drugs.com/cdi/frovatriptan.html
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