Chemistry:Frovatriptan

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Frovatriptan, sold under the brand name Frova among others, is a triptan medication developed by Vernalis for the treatment of migraine headaches[1] and for short term prevention of menstrual migraine.[2][3] The product is licensed to Endo Pharmaceuticals in North America and Menarini in Europe.[4]

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:

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

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)
38% (Emax)
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 ND
SERT ND
NET ND
DAT ND
Notes: The smaller the value, the more avidly the drug binds to the site. All proteins are human unless otherwise specified. Refs: [5][6][7][8][3][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. Frovatriptan inhibits excessive dilation of arteries that supply blood to the head.{{Citation needed|date=July 2025} ovatriptan 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

  • Triptan
  • Tetrahydrocarbazolamine
  • LY-344864

References

  1. ↑ "Spotlight on frovatriptan: a review of its efficacy in the treatment of migraine". Drug Design, Development and Therapy 10: 3225–3236. 2016. doi:10.2147/DDDT.S105932. PMID 27757013. 
  2. ↑ "A review of frovatriptan for the treatment of menstrual migraine". International Journal of Women's Health 6: 523–35. 2014. doi:10.2147/IJWH.S63444. PMID 24904224. 
  3. ↑ 3.0 3.1 "Frovatriptan: a selective type 1B/1D serotonin receptor agonist for the treatment of migraine headache". Drugs Today (Barc) 38 (9): 615–629. September 2002. doi:10.1358/dot.2002.38.9.696537. PMID 12582449. 
  4. ↑ "Frova". Vernalis. http://www.vernalis.com/ver/rdc2/pain/frovatriptan/. 
  5. ↑ Liu, Tiqing. "Simple Search Results". https://www.bindingdb.org/rwd/bind/tabLuceneResult.jsp?thisInput=frovatriptan. 
  6. ↑ "Pharmacology of triptans". Emerging Drugs 4 (1): 107–125. 1999. doi:10.1517/14728214.4.1.107. ISSN 1361-9195. 
  7. ↑ "Triptans in migraine: a comparative review of pharmacology, pharmacokinetics and efficacy". Drugs 60 (6): 1259–1287. December 2000. doi:10.2165/00003495-200060060-00003. PMID 11152011. 
  8. ↑ "Success and failure of triptans". The Journal of Headache and Pain 2 (1): 3–11. 2001. doi:10.1007/s101940170040. ISSN 1129-2369. 
  9. ↑ "Coronary Side Effects of Antimigraine Drugs From Patient to Receptor". 22 December 1999. https://repub.eur.nl/pub/16171/. "Table 1.2 Receptor binding properties (pKi values) of sumatriptan and second-generation triptans at 5-HT receptors. [...]" 
  10. ↑ "Vascular Effects of Antimigraine Drugs: pharmacology of human in vitro models in migraine". 13 March 2002. https://repub.eur.nl/pub/16167/. "Table 1.2 Receptor binding properties (pKi values) of the triptans at human 5-HT receptors. [...]" 
  11. ↑ "Preclinical pharmacological profile of the selective 5-HT1F receptor agonist lasmiditan". Cephalalgia 30 (10): 1159–1169. October 2010. doi:10.1177/0333102410370873. PMID 20855361. 
  12. ↑ 12.0 12.1 12.2 12.3 "Characterization of binding, functional activity, and contractile responses of the selective 5-HT1F receptor agonist lasmiditan". British Journal of Pharmacology 176 (24): 4681–4695. December 2019. doi:10.1111/bph.14832. 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. ↑ "Lasmiditan hydrochloride". Drugs of the Future 37 (10): 709. 2012. doi:10.1358/dof.2012.037.010.1873629. ISSN 0377-8282. http://journals.prous.com/journals/servlet/xmlxsl/pk_journals.xml_summary_pr?p_JournalId=2&p_RefId=1873629&p_IsPs=N. Retrieved 19 June 2025. 
  14. ↑ "Evidence-based symptomatic treatment of migraine". Migraine Management. Handbook of Clinical Neurology. 199. 2024. pp. 203–218. doi:10.1016/B978-0-12-823357-3.00004-5. ISBN 978-0-12-823357-3. 
  15. ↑ "Pharmacology of the selective 5-HT(1B/1D) agonist frovatriptan". Headache 42 (Suppl 2): S47–S53. April 2002. doi:10.1046/j.1526-4610.42.s2.2.x. PMID 12028320. 
  16. ↑ Balbisi, Ebrahim (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. PMID 18360605. 
  17. ↑ 17.0 17.1 "Current and emerging second-generation triptans in acute migraine therapy: a comparative review". J Clin Pharmacol 40 (7): 687–700. July 2000. doi:10.1177/00912700022009431. PMID 10883409. 
  18. ↑ "Frovatriptan". https://pubchem.ncbi.nlm.nih.gov/compound/77992. 
  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. ↑ "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. July 1997. doi:10.1097/00005344-199707000-00020. PMID 9268233. 
  21. ↑ "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. August 1998. doi:10.1097/00005344-199808000-00008. PMID 9700983. 
  22. ↑ "Drug Approval Package: Frova (Frovatriptan) NDA #21-006". 20 November 2001. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-006_Frova.cfm. 
  23. ↑ "Patient Information Sheet -- Frovatriptan succinate (marketed as Frova)". Food and Drug Administration. July 2006. https://www.fda.gov/cder/drug/InfoSheets/patient/frovatripanPIS.htm. 



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