Frovatriptan

Last updated

Frovatriptan
Frovatriptan structure.svg
Frovatriptan 3D BS.png
Clinical data
Trade names Frova
Other namesSB-209509; SB209509; EN-3266; EN3266; VML-251; VML251
AHFS/Drugs.com Monograph
MedlinePlus a604013
License data
Pregnancy
category
  • AU:B3
Routes of
administration 		Oral
Drug class Serotonin 5-HT1B, 5-HT1D, 5-HT1F, and 5-HT7 receptor agonist
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability 20–30%
Metabolism Liver
Elimination half-life 26–30 hours [1]
Excretion Kidney
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
Formula C14H17N3O
Molar mass 243.310 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 Yes check.svgY
  • Key:XPSQPHWEGNHMSK-SECBINFHSA-N Yes check.svgY
   (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]

Contents

Medical uses

Frovatriptan is used in the treatment of migraine.

Available forms

It is available as 2.5 mg tablets.

Contraindications

Frovatriptan should not be given to patients with:

Side effects

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

Pharmacodynamics

Frovatriptan activities
Target Affinity (Ki, nM)
5-HT1A 50–62 (Ki)
759–>10,000 (EC50 Tooltip half-maximal effective concentration)
38% (Emax Tooltip 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
TAAR1 Tooltip Trace amine-associated receptor 1ND
SERT Tooltip Serotonin transporterND
NET Tooltip Norepinephrine transporterND
DAT Tooltip Dopamine transporterND
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

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

Chemistry

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

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

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

See also

References

  1. 1 2 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. 1 2 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. 1 2 3 4 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. 1 2 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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