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<ref name="pmid27757013">Template:Cite journal</ref> and for short term prevention of menstrual migraine.<ref name="pmid24904224">Template:Cite journal</ref><ref name="ColeRabasseda2002">Template:Cite journal</ref> The product is licensed to Endo Pharmaceuticals in North America and Menarini in Europe.<ref>Template:Cite web</ref>
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
| Target | Affinity (Ki, nM) |
|---|---|
| 5-HT1A | 50–62 (Ki) 759–>10,000 (Template:Abbrlink) 38% (Template:Abbrlink) |
| 5-HT1B | 2.5–46 (Ki) 6.3–20 (Template:Abbr) 92% (Template:Abbr) |
| 5-HT1D | 1.7–10 (Ki) 2–5 (Template:Abbr) 98% (Template:Abbr) |
| 5-HT1E | >1,000 (Ki) 6,610–>10,000 (Template:Abbr) 44% (Template:Abbr) |
| 5-HT1F | 63–120 (Ki) 79–447 (Template:Abbr) 46% (Template:Abbr) |
| 5-HT2A | >10,000 (Ki) >10,000 (Template:Abbr) |
| 5-HT2B | >10,000 (Ki) >10,000 (Template:Abbr) |
| 5-HT2C | >5,000 (Ki) Template:Abbr (Template:Abbr) |
| 5-HT3 | >1,000 (mouse/rat) |
| 5-HT4 | Template:Abbr |
| 5-HT5A | Template:Abbr |
| 5-HT6 | Template:Abbr |
| 5-HT7 | 107–200 (Ki) 38 (Template:Abbr) |
| α1 | >10,000 (rat) |
| α1A–α1D | Template:Abbr |
| α2A–α2C | Template:Abbr |
| β1–β3 | Template:Abbr |
| D1 | >10,000 |
| D2 | >10,000 |
| D3 | >10,000 |
| D4–D5 | Template:Abbr |
| H1 | >10,000 (guinea pig) |
| H2–H4 | Template:Abbr |
| M1–M5 | Template:Abbr |
| I1, I2 | Template:Abbr |
| σ1, σ2 | Template:Abbr |
| Template:Abbrlink | Template:Abbr |
| Template:Abbrlink | Template:Abbr |
| Template:Abbrlink | Template:Abbr |
| Template:Abbrlink | Template:Abbr |
| Notes: The smaller the value, the more avidly the drug binds to the site. All proteins are human unless otherwise specified. Refs: <ref name="BindingDB">Template:Cite web</ref><ref name="DeVriesVillalónSaxena1999">Template:Cite journal</ref><ref name="Tfelt-HansenDeVriesSaxena2000">Template:Cite journal</ref><ref name="SaxenaTfelt-Hansen2001">Template:Cite journal</ref><ref name="ColeRabasseda2002" /><ref name="Brink1999">Template:Cite web</ref><ref name="Broek2002">Template:Cite web</ref> <ref name="NelsonPhebusJohnson2010">Template:Cite journal</ref><ref name="Rubio-BeltránLabastida-RamírezHaanes2019">Template:Cite journal</ref><ref name="ReuterNeeb2012">Template:Cite journal</ref><ref name="MitsikostasWard2024">Template:Cite book</ref><ref name="Comer2002">Template:Cite journal</ref> | |
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.<ref name="Rubio-BeltránLabastida-RamírezHaanes2019" /> It has no significant effects on the GABAA mediated channel activity and benzodiazepine binding sites.Template:Citation needed Frovatriptan inhibits excessive dilation of arteries that supply blood to the head.Template:Citation needed Uniquely among most triptans, frovatriptan is also a relatively potent serotonin 5-HT7 receptor agonist.<ref name="Rubio-BeltránLabastida-RamírezHaanes2019" /> It is inactive at the serotonin 5-HT2A and 5-HT2B receptors.<ref name="Rubio-BeltránLabastida-RamírezHaanes2019" />
Pharmacokinetics
Frovatriptan has a terminal elimination half-life of approximately 26 hours, making it the longest within its class.<ref>Template:Cite journal</ref>
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.<ref name="DeleuHanssens2000">Template:Cite journal</ref> It can be thought of as a 5-substituted and side chain-cyclized derivative of N-methyltryptamine (NMT).<ref name="DeleuHanssens2000" />
The experimental log P of frovatriptan is 0.9 and its predicted log P is 1.2.<ref name="PubChem">Template:Cite web</ref>
History
Frovatriptan was first described in the scientific literature by 1997.<ref name="BrownParsonsRaval1996">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).</ref><ref name="ParsonsParkerRaval1997">Template:Cite journal</ref><ref name="ParsonsRavalSmith1998">Template:Cite journal</ref> It was approved for medical use in the United States in 2001.<ref name="FDA2001">Template:Cite web</ref>
Society and culture
Legal status
Frovatriptan is available only by prescription in the United States and Canada.<ref>Template:Cite web</ref>
See also
References
Template:Antimigraine preparations Template:Serotonin receptor modulators Template:Tryptamines Template:Portal bar Template:Authority control