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Frovatriptan

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Frovatriptan
Clinical data
Trade namesFrova
Other namesSB-209509; SB209509; EN-3266; EN3266; VML-251; VML251
AHFS/Drugs.comMonograph
MedlinePlusa604013
License data
Pregnancy
category
  • AU: B3
Routes of
administration		Oral
Drug classSerotonin 5-HT1B, 5-HT1D, 5-HT1F, and 5-HT7 receptor agonist
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability20–30%
MetabolismLiver
Elimination half-life26–30 hours[1]
ExcretionKidney
Identifiers
  • (+)-(R)-3-Methylamino-6-carboxamido-1,2,3,4-tetrahydrocarbazole
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC14H17N3O
Molar mass243.310 g·mol−1
3D model (JSmol)
  • CN[C@@H]3CCc2[nH]c1ccc(C(N)=O)cc1c2C3
  • 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 checkY
  • Key:XPSQPHWEGNHMSK-SECBINFHSA-N checkY
  (verify)

Frovatriptan, sold under the brand name Frova among others, is a triptan medication developed by Vernalis for the treatment of migraine headaches[2] and for short term prevention of menstrual migraine.[3][4] The product is licensed to Endo Pharmaceuticals in North America and Menarini in Europe.[5]

Medical uses

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Frovatriptan is used in the treatment of migraine.

Available forms

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It is available as 2.5 mg tablets.

Contraindications

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Frovatriptan should not be given to patients with:

  • Ischemic heart disease
  • Cerebrovascular syndrome
  • Peripheral vascular disease
  • Uncontrolled hypertension
  • Hemiplegic or basilar migraine

Side effects

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Rare, but serious cardiac events have been reported in patients with risk factors predictive of CAD. These include: coronary artery vasospasm, transient myocardial ischemia, myocardial infarction, ventricular tachycardia and ventricular fibrillation.

Pharmacology

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Pharmacodynamics

[edit]
Further information: Serotonin receptor agonist and Triptan § Mechanism of action
Frovatriptan activities
Target Affinity (Ki, nM)
5-HT1A 50–62 (Ki)
759–>10,000 (EC50Tooltip half-maximal effective concentration)
38% (EmaxTooltip maximal efficacy)
5-HT1B 2.5–46 (Ki)
6.3–20 (EC50)
92% (Emax)
5-HT1D 1.7–10 (Ki)
2–5 (EC50)
98% (Emax)
5-HT1E >1,000 (Ki)
6,610–>10,000 (EC50)
44% (Emax)
5-HT1F 63–120 (Ki)
79–447 (EC50)
46% (Emax)
5-HT2A >10,000 (Ki)
>10,000 (EC50)
5-HT2B >10,000 (Ki)
>10,000 (EC50)
5-HT2C >5,000 (Ki)
ND (EC50)
5-HT3 >1,000 (mouse/rat)
5-HT4 ND
5-HT5A ND
5-HT6 ND
5-HT7 107–200 (Ki)
38 (EC50)
α1 >10,000 (rat)
α1A–α1D ND
α2A–α2C ND
β1–β3 ND
D1 >10,000
D2 >10,000
D3 >10,000
D4–D5 ND
H1 >10,000 (guinea pig)
H2–H4 ND
M1–M5 ND
I1, I2 ND
σ1, σ2 ND
TAAR1Tooltip Trace amine-associated receptor 1 ND
SERTTooltip Serotonin transporter ND
NETTooltip Norepinephrine transporter ND
DATTooltip Dopamine transporter ND
Notes: The smaller the value, the more avidly the drug binds to the site. All proteins are human unless otherwise specified. Refs: [6][7][1][8][4][9][10]
[11][12][13][14][15]

Frovatriptan is a serotonin receptor agonist, with high affinity for the serotonin 5-HT1B and 5-HT1D receptors and with weaker activity at the serotonin 5-HT1F receptor.[12] It has no significant effects on the GABAA mediated channel activity and benzodiazepine binding sites.[citation needed] Frovatriptan inhibits excessive dilation of arteries that supply blood to the head.[citation needed] Uniquely among most triptans, frovatriptan is also a relatively potent serotonin 5-HT7 receptor agonist.[12] It is inactive at the serotonin 5-HT2A and 5-HT2B receptors.[12]

Pharmacokinetics

[edit]

Frovatriptan has a terminal elimination half-life of approximately 26 hours, making it the longest within its class.[16]

Chemistry

[edit]

Frovatriptan's chemical structure is unusual among triptans, with other triptans being simple tryptamines or closely related compounds but frovatriptan instead being a tricyclic cyclized tryptamine and tetrahydrocarbazolamine derivative.[17] It can be thought of as a 5-substituted and side chain-cyclized derivative of N-methyltryptamine (NMT).[17]

The experimental log P of frovatriptan is 0.9 and its predicted log P is 1.2.[18]

History

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Frovatriptan was first described in the scientific literature by 1997.[19][20][21] It was approved for medical use in the United States in 2001.[22]

Society and culture

[edit]
[edit]

Frovatriptan is available only by prescription in the United States and Canada.[23]

See also

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References

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  1. ^ a b Tfelt-Hansen P, De Vries P, Saxena PR (December 2000). "Triptans in migraine: a comparative review of pharmacology, pharmacokinetics and efficacy". Drugs. 60 (6): 1259–1287. doi:10.2165/00003495-200060060-00003. PMID 11152011.
  2. ^ Allais G, Benedetto C (2016). "Spotlight on frovatriptan: a review of its efficacy in the treatment of migraine". Drug Design, Development and Therapy. 10: 3225–3236. doi:10.2147/DDDT.S105932. PMC 5055118. PMID 27757013.
  3. ^ MacGregor EA (2014). "A review of frovatriptan for the treatment of menstrual migraine". International Journal of Women's Health. 6: 523–35. doi:10.2147/IJWH.S63444. PMC 4039425. PMID 24904224.
  4. ^ a b Cole P, Rabasseda X (September 2002). "Frovatriptan: a selective type 1B/1D serotonin receptor agonist for the treatment of migraine headache". Drugs Today (Barc). 38 (9): 615–629. doi:10.1358/dot.2002.38.9.696537. PMID 12582449.
  5. ^ "Frova". Vernalis. Archived from the original on 27 September 2007. Retrieved 28 November 2007.
  6. ^ Liu T. "Simple Search Results". BindingDB. Retrieved 28 July 2025.
  7. ^ De Vries P, Villalón CM, Saxena PR (1999). "Pharmacology of triptans". Emerging Drugs. 4 (1): 107–125. doi:10.1517/14728214.4.1.107. ISSN 1361-9195.
  8. ^ Saxena PR, Tfelt-Hansen P (2001). "Success and failure of triptans". The Journal of Headache and Pain. 2 (1): 3–11. doi:10.1007/s101940170040. ISSN 1129-2369. PMC 3611827.
  9. ^ van den Brink M (22 December 1999). "Coronary Side Effects of Antimigraine Drugs From Patient to Receptor". RePub, Erasmus University Repository. Retrieved 19 June 2025. Table 1.2 Receptor binding properties (pKi values) of sumatriptan and second-generation triptans at 5-HT receptors. [...]
  10. ^ van den Broek RW (13 March 2002). "Vascular Effects of Antimigraine Drugs: pharmacology of human in vitro models in migraine". RePub, Erasmus University Repository. Retrieved 19 June 2025. Table 1.2 Receptor binding properties (pKi values) of the triptans at human 5-HT receptors. [...]
  11. ^ Nelson DL, Phebus LA, Johnson KW, Wainscott DB, Cohen ML, Calligaro DO, et al. (October 2010). "Preclinical pharmacological profile of the selective 5-HT1F receptor agonist lasmiditan". Cephalalgia. 30 (10): 1159–1169. doi:10.1177/0333102410370873. PMID 20855361.
  12. ^ a b c d Rubio-Beltrán E, Labastida-Ramírez A, Haanes KA, van den Bogaerdt A, Bogers AJ, Zanelli E, et al. (December 2019). "Characterization of binding, functional activity, and contractile responses of the selective 5-HT1F receptor agonist lasmiditan". British Journal of Pharmacology. 176 (24): 4681–4695. doi:10.1111/bph.14832. PMC 6965684. PMID 31418454. TABLE 1 Summary of pIC50 (negative logarithm of the molar concentration of these compounds at which 50% of the radioligand is displaced) and pKi (negative logarithm of the molar concentration of the Ki ) values of individual antimigraine drugs at 5‐HT receptors [...] TABLE 2 Summary of pEC50 values of cAMP (5‐HT1A/B/E/F and 5‐HT7), GTPγS (5‐HT1A/B/D/E/F), and IP (5‐HT2) assays of individual antimigraine drugs at 5‐HT receptors [...]
  13. ^ Reuter U, Neeb L (2012). "Lasmiditan hydrochloride". Drugs of the Future. 37 (10): 709. doi:10.1358/dof.2012.037.010.1873629. ISSN 0377-8282. Retrieved 19 June 2025.
  14. ^ Mitsikostas DD, Ward TN (2024). "Evidence-based symptomatic treatment of migraine". Migraine Management. Handbook of Clinical Neurology. Vol. 199. pp. 203–218. doi:10.1016/B978-0-12-823357-3.00004-5. ISBN 978-0-12-823357-3. PMID 38307647.
  15. ^ Comer MB (April 2002). "Pharmacology of the selective 5-HT(1B/1D) agonist frovatriptan". Headache. 42 (Suppl 2): S47 – S53. doi:10.1046/j.1526-4610.42.s2.2.x. PMID 12028320.
  16. ^ Balbisi E (September 2006). "Frovatriptan: A Review of Pharmacology, Pharmacokinetics and Clinical Potential in the Treatment of Menstrual Migraine". Therapeutics and Clinical Risk Management. 2 (3): 303–308. doi:10.2147/tcrm.2006.2.3.303. PMC 1936266. PMID 18360605.
  17. ^ a b Deleu D, Hanssens Y (July 2000). "Current and emerging second-generation triptans in acute migraine therapy: a comparative review". J Clin Pharmacol. 40 (7): 687–700. doi:10.1177/00912700022009431. PMID 10883409.
  18. ^ "Frovatriptan". PubChem. Retrieved 29 July 2025.
  19. ^ Brown, A. M., Parsons, A. A., Raval, P., Porter, R., Tilford, N. S., Gager, T. L., ... & King, F. D. (1996, October). SB 209509 (VML 251), a potent constrictor of rabbit basilar artery with high affinity and selectivity for human 5-HT1D receptors. In BRITISH JOURNAL OF PHARMACOLOGY (Vol. 119, pp. P110-P110).
  20. ^ Parsons AA, Parker SG, Raval P, Campbell CA, Lewis VA, Griffiths R, et al. (July 1997). "Comparison of the cardiovascular effects of the novel 5-HT(1B/1D) receptor agonist, SB 209509 (VML251), and sumatriptan in dogs". J Cardiovasc Pharmacol. 30 (1): 136–141. doi:10.1097/00005344-199707000-00020. PMID 9268233.
  21. ^ Parsons AA, Raval P, Smith S, Tilford N, King FD, Kaumann AJ, et al. (August 1998). "Effects of the novel high-affinity 5-HT(1B/1D)-receptor ligand frovatriptan in human isolated basilar and coronary arteries". J Cardiovasc Pharmacol. 32 (2): 220–224. doi:10.1097/00005344-199808000-00008. PMID 9700983.
  22. ^ "Drug Approval Package: Frova (Frovatriptan) NDA #21-006". accessdata.fda.gov. 20 November 2001. Retrieved 28 July 2025.
  23. ^ "Patient Information Sheet -- Frovatriptan succinate (marketed as Frova)". Food and Drug Administration. July 2006. Archived from the original on 29 September 2007. Retrieved 28 November 2007.
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