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{{Short description|Chemical compound}}
{{Use dmy dates|date=April 2025}}
{{cs1 config |name-list-style=vanc |display-authors=6}}
{{Infobox drug
| Verifiedfields = verified
| Watchedfields = verified
| verifiedrevid = 461114004
| image = Frovatriptan structure.svg
| alt =
| image2 = Frovatriptan 3D BS.png
| alt2 =


| pronounce =
| tradename = Frova
| Drugs.com = {{drugs.com|monograph|frova}}
| MedlinePlus = a604013
| DailyMedID = Frovatriptan
| pregnancy_AU = B3
| pregnancy_AU_comment =
| pregnancy_category =
| routes_of_administration = [[Oral administration|Oral]]
| class = [[Serotonin]] [[5-HT1B receptor|5-HT1B]], [[5-HT1D receptor|5-HT1D]], [[5-HT1F receptor|5-HT1F]], and [[5-HT7 receptor|5-HT7 receptor]] [[agonist]]
| ATC_prefix = N02
| ATC_suffix = CC07
| ATC_supplemental =


| legal_AU = 
| legal_AU_comment =
| legal_BR = 
| legal_BR_comment =
| legal_CA = Rx-only
| legal_CA_comment =
| legal_DE = 
| legal_DE_comment =
| legal_NZ = 
| legal_NZ_comment =
| legal_UK = 
| legal_UK_comment =
| legal_US = Rx-only
| legal_US_comment =
| legal_EU =
| legal_EU_comment =
| legal_UN = 
| legal_UN_comment =
| legal_status = 


| bioavailability = 20–30%
| protein_bound =
| metabolism = [[Liver]]
| metabolites =
| onset =
| elimination_half-life = 26–30 hours<ref name="Tfelt-HansenDeVriesSaxena2000" />
| duration_of_action =
| excretion = [[Kidney]]


| index2_label = succinate
| CAS_number_Ref = {{cascite|correct|CAS}}
| CAS_number = 158747-02-5
| CAS_number2_Ref = {{cascite|correct|CAS}}
| CAS_number2 = 158930-17-7
| PubChem = 77992
| IUPHAR_ligand = 7191
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB00998
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 70378
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = H82Q2D5WA7
| UNII2_Ref = {{fdacite|correct|FDA}}
| UNII2 = D28J6W18HY
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D07997
| ChEBI =
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 1279
| NIAID_ChemDB =
| PDB_ligand =
| synonyms = SB-209509; SB209509; EN-3266; EN3266; VML-251; VML251


| IUPAC_name = (+)-(''R'')-3-Methylamino-6-carboxamido-1,2,3,4-tetrahydrocarbazole
| C=14 | H=17 | N=3 | O=1
| SMILES = CN[C@@H]3CCc2[nH]c1ccc(C(N)=O)cc1c2C3
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 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
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = XPSQPHWEGNHMSK-SECBINFHSA-N


| density =
| density_notes =
| melting_point =
| melting_high =
| melting_notes =
| boiling_point =
| boiling_notes =
| solubility =
| sol_units =
| specific_rotation =
}}

'''Frovatriptan''', sold under the brand name '''Frova''' among others, is a [[triptan]] [[medication]] developed by [[Vernalis plc|Vernalis]] for the treatment of [[migraine]] [[headache]]s<ref name="pmid27757013">{{cite journal | vauthors = Allais G, Benedetto C | title = Spotlight on frovatriptan: a review of its efficacy in the treatment of migraine | journal = Drug Design, Development and Therapy | volume = 10 | issue = | pages = 3225–3236 | date = 2016 | pmid = 27757013 | pmc = 5055118 | doi = 10.2147/DDDT.S105932 | doi-access = free }}</ref> and for short term prevention of [[menstrual migraine]].<ref name="pmid24904224">{{cite journal | vauthors = MacGregor EA | title = A review of frovatriptan for the treatment of menstrual migraine | journal = International Journal of Women's Health | volume = 6 | issue = | pages = 523–35 | date = 2014 | pmid = 24904224 | pmc = 4039425 | doi = 10.2147/IJWH.S63444 | doi-access = free }}</ref><ref name="ColeRabasseda2002">{{cite journal | vauthors = Cole P, Rabasseda X | title = Frovatriptan: a selective type 1B/1D serotonin receptor agonist for the treatment of migraine headache | journal = Drugs Today (Barc) | volume = 38 | issue = 9 | pages = 615–629 | date = September 2002 | pmid = 12582449 | doi = 10.1358/dot.2002.38.9.696537 | url = }}</ref> The product is licensed to [[Endo Pharmaceuticals]] in North America and [[Menarini]] in Europe.<ref>{{cite web|title=Frova |url=http://www.vernalis.com/ver/rdc2/pain/frovatriptan/ |publisher=Vernalis |access-date=2007-11-28 |archive-url=https://web.archive.org/web/20070927225521/http://www.vernalis.com/ver/rdc2/pain/frovatriptan/ |archive-date=2007-09-27 |url-status=dead }}</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===
{{Further|Serotonin receptor agonist|Triptan#Mechanism of action}}
{| class="wikitable floatleft" style="font-size:small;"
|+ {{Nowrap|Frovatriptan activities}}
|-
! [[Biological target|Target]] !! [[Affinity (pharmacology)|Affinity]] (Ki, nM)
|-
| [[5-HT1A receptor|5-HT1A]] || 50–62 (Ki) 759–>10,000 ({{Abbrlink|EC50|half-maximal effective concentration}}) 38% ({{Abbrlink|Emax|maximal efficacy}})
|-
| [[5-HT1B receptor|5-HT1B]] || 2.5–46 (Ki) 6.3–20 ({{Abbr|EC50|half-maximal effective concentration}}) 92% ({{Abbr|Emax|maximal efficacy}})
|-
| [[5-HT1D receptor|5-HT1D]] || 1.7–10 (Ki) 2–5 ({{Abbr|EC50|half-maximal effective concentration}}) 98% ({{Abbr|Emax|maximal efficacy}})
|-
| [[5-HT1E receptor|5-HT1E]] || >1,000 (Ki) 6,610–>10,000 ({{Abbr|EC50|half-maximal effective concentration}}) 44% ({{Abbr|Emax|maximal efficacy}})
|-
| [[5-HT1F receptor|5-HT1F]] || 63–120 (Ki) 79–447 ({{Abbr|EC50|half-maximal effective concentration}}) 46% ({{Abbr|Emax|maximal efficacy}})
|-
| [[5-HT2A receptor|5-HT2A]] || >10,000 (Ki) >10,000 ({{Abbr|EC50|half-maximal effective concentration}})
|-
| [[5-HT2B receptor|5-HT2B]] || >10,000 (Ki) >10,000 ({{Abbr|EC50|half-maximal effective concentration}})
|-
| [[5-HT2C receptor|5-HT2C]] || >5,000 (Ki) {{Abbr|ND|No data}} ({{Abbr|EC50|half-maximal effective concentration}})
|-
| [[5-HT3 receptor|5-HT3]] || >1,000 (mouse/rat)
|-
| [[5-HT4 receptor|5-HT4]] || {{Abbr|ND|No data}}
|-
| [[5-HT5A receptor|5-HT5A]] || {{Abbr|ND|No data}}
|-
| [[5-HT6 receptor|5-HT6]] || {{Abbr|ND|No data}}
|-
| [[5-HT7 receptor|5-HT7]] || 107–200 (Ki) 38 ({{Abbr|EC50|half-maximal effective concentration}})
|-
| [[Alpha-1 adrenergic receptor|α1]] || >10,000 (rat)
|-
| [[Alpha-1A adrenergic receptor|α1A]]–[[Alpha-1D adrenergic receptor|α1D]] || {{Abbr|ND|No data}}
|-
| [[Alpha-2A adrenergic receptor|α2A]]–[[Alpha-2C adrenergic receptor|α2C]] || {{Abbr|ND|No data}}
|-
| [[Beta-1 adrenergic receptor|β1]]–[[Beta-3 adrenergic receptor|β3]] || {{Abbr|ND|No data}}
|-
| [[D1 receptor|D1]] || >10,000
|-
| [[D2 receptor|D2]] || >10,000
|-
| [[D3 receptor|D3]] || >10,000
|-
| [[D4 receptor|D4]]–[[D5 receptor|D5]] || {{Abbr|ND|No data}}
|-
| [[H1 receptor|H1]] || >10,000 (guinea pig)
|-
| [[H2 receptor|H2]]–[[H4 receptor|H4]] || {{Abbr|ND|No data}}
|-
| [[Muscarinic acetylcholine M1 receptor|M1]]–[[M5 receptor|M5]] || {{Abbr|ND|No data}}
|-
| [[I1 receptor|I1]], [[I2 receptor|I2]] || {{Abbr|ND|No data}}
|-
| [[Sigma-1 receptor|σ1]], [[Sigma-2 receptor|σ2]] || {{Abbr|ND|No data}}
|-
| {{Abbrlink|TAAR1|Trace amine-associated receptor 1}} || {{Abbr|ND|No data}}
|-
| {{Abbrlink|SERT|Serotonin transporter}} || {{Abbr|ND|No data}}
|-
| {{Abbrlink|NET|Norepinephrine transporter}} || {{Abbr|ND|No data}}
|-
| {{Abbrlink|DAT|Dopamine transporter}} || {{Abbr|ND|No data}}
|- class="sortbottom"
| colspan="2" style="width: 1px; background-color:#eaecf0; text-align: center;" | '''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">{{cite web | last=Liu | first=Tiqing | title=Simple Search Results | website=BindingDB | url=https://www.bindingdb.org/rwd/bind/tabLuceneResult.jsp?thisInput=frovatriptan | access-date=28 July 2025}}</ref><ref name="DeVriesVillalónSaxena1999">{{cite journal | vauthors = De Vries P, Villalón CM, Saxena PR | title=Pharmacology of triptans | journal=Emerging Drugs | volume=4 | issue=1 | date=1999 | issn=1361-9195 | doi=10.1517/14728214.4.1.107 | pages=107–125 }}</ref><ref name="Tfelt-HansenDeVriesSaxena2000">{{cite journal | vauthors = Tfelt-Hansen P, De Vries P, Saxena PR | title = Triptans in migraine: a comparative review of pharmacology, pharmacokinetics and efficacy | journal = Drugs | volume = 60 | issue = 6 | pages = 1259–1287 | date = December 2000 | pmid = 11152011 | doi = 10.2165/00003495-200060060-00003 }}</ref><ref name="SaxenaTfelt-Hansen2001">{{cite journal | vauthors = Saxena PR, Tfelt-Hansen P | title=Success and failure of triptans | journal=The Journal of Headache and Pain | volume=2 | issue=1 | date=2001 | issn=1129-2369 | pmc=3611827 | doi=10.1007/s101940170040 | doi-access=free | pages=3–11 }}</ref><ref name="ColeRabasseda2002" /><ref name="Brink1999">{{cite web | vauthors = van den Brink M | title=Coronary Side Effects of Antimigraine Drugs From Patient to Receptor | website= RePub, Erasmus University Repository | date=22 December 1999 | url=https://repub.eur.nl/pub/16171/ | access-date=19 June 2025 | quote = Table 1.2 Receptor binding properties (pKi values) of sumatriptan and second-generation triptans at 5-HT receptors. [...]}}</ref><ref name="Broek2002">{{cite web | vauthors = van den Broek RW | title=Vascular Effects of Antimigraine Drugs: pharmacology of human in vitro models in migraine | website= RePub, Erasmus University Repository | date=13 March 2002 | url=https://repub.eur.nl/pub/16167/ | access-date=19 June 2025 | quote=Table 1.2 Receptor binding properties (pKi values) of the triptans at human 5-HT receptors. [...]}}</ref> <ref name="NelsonPhebusJohnson2010">{{cite journal | vauthors = Nelson DL, Phebus LA, Johnson KW, Wainscott DB, Cohen ML, Calligaro DO, Xu YC | title = Preclinical pharmacological profile of the selective 5-HT1F receptor agonist lasmiditan | journal = Cephalalgia | volume = 30 | issue = 10 | pages = 1159–1169 | date = October 2010 | pmid = 20855361 | doi = 10.1177/0333102410370873 | url = }}</ref><ref name="Rubio-BeltránLabastida-RamírezHaanes2019">{{cite journal | vauthors = Rubio-Beltrán E, Labastida-Ramírez A, Haanes KA, van den Bogaerdt A, Bogers AJ, Zanelli E, Meeus L, Danser AH, Gralinski MR, Senese PB, Johnson KW, Kovalchin J, Villalón CM, MaassenVanDenBrink A | title = Characterization of binding, functional activity, and contractile responses of the selective 5-HT1F receptor agonist lasmiditan | journal = British Journal of Pharmacology | volume = 176 | issue = 24 | pages = 4681–4695 | date = December 2019 | pmid = 31418454 | pmc = 6965684 | doi = 10.1111/bph.14832 | quote = 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 [...] }}</ref><ref name="ReuterNeeb2012">{{cite journal | vauthors = Reuter U, Neeb L | title=Lasmiditan hydrochloride | journal=Drugs of the Future | volume=37 | issue=10 | date=2012 | issn=0377-8282 | doi=10.1358/dof.2012.037.010.1873629 | page=709 | url=http://journals.prous.com/journals/servlet/xmlxsl/pk_journals.xml_summary_pr?p_JournalId=2&p_RefId=1873629&p_IsPs=N | access-date=19 June 2025}}</ref><ref name="MitsikostasWard2024">{{cite book | vauthors = Mitsikostas DD, Ward TN | title = Migraine Management | chapter = Evidence-based symptomatic treatment of migraine | series = Handbook of Clinical Neurology | volume = 199 | pages = 203–218 | date = 2024 | pmid = 38307647 | doi = 10.1016/B978-0-12-823357-3.00004-5 | isbn = 978-0-12-823357-3 }}</ref><ref name="Comer2002">{{cite journal | vauthors = Comer MB | title = Pharmacology of the selective 5-HT(1B/1D) agonist frovatriptan | journal = Headache | volume = 42 | issue = Suppl 2 | pages = S47–S53 | date = April 2002 | pmid = 12028320 | doi = 10.1046/j.1526-4610.42.s2.2.x }}</ref>
|}

Frovatriptan is a [[serotonin receptor]] [[agonist]], with high [[affinity (pharmacology)|affinity]] for the [[serotonin]] [[5-HT1B receptor|5-HT1B]] and [[5-HT1D receptor|5-HT1D receptor]]s and with weaker activity at the serotonin [[5-HT1F receptor|5-HT1F receptor]].<ref name="Rubio-BeltránLabastida-RamírezHaanes2019" /> It has no significant effects on the GABAA mediated channel activity and [[benzodiazepine]] binding sites.{{Citation needed|date=July 2025}} Frovatriptan inhibits excessive dilation of arteries that supply blood to the head.{{Citation needed|date=July 2025}} Uniquely among most triptans, frovatriptan is also a relatively [[potency (pharmacology)|potent]] [[serotonin]] [[5-HT7 receptor|5-HT7 receptor]] [[agonist]].<ref name="Rubio-BeltránLabastida-RamírezHaanes2019" /> It is inactive at the serotonin [[5-HT2A receptor|5-HT2A]] and [[5-HT2B receptor|5-HT2B receptor]]s.<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>{{Cite journal|last=Balbisi|first=Ebrahim|date=September 2006|title=Frovatriptan: A Review of Pharmacology, Pharmacokinetics and Clinical Potential in the Treatment of Menstrual Migraine|journal=Therapeutics and Clinical Risk Management|volume=2|issue=3|pages=303–308|doi=10.2147/tcrm.2006.2.3.303|pmid=18360605|pmc=1936266 |doi-access=free }}</ref>

==Chemistry==
Frovatriptan's [[chemical structure]] is unusual among [[triptan]]s, with other triptans being simple [[substituted tryptamine|tryptamine]]s or closely related compounds but frovatriptan instead being a [[tricyclic compound|tricyclic]] [[cyclized tryptamine]] and [[tetrahydrocarbazolamine]] [[chemical derivative|derivative]].<ref name="DeleuHanssens2000">{{cite journal | vauthors = Deleu D, Hanssens Y | title = Current and emerging second-generation triptans in acute migraine therapy: a comparative review | journal = J Clin Pharmacol | volume = 40 | issue = 7 | pages = 687–700 | date = July 2000 | pmid = 10883409 | doi = 10.1177/00912700022009431 | url = }}</ref> It can be thought of as a 5-substituted and [[side chain]]-[[cyclic compound|cyclized]] [[chemical derivative|derivative]] of [[N-methyltryptamine|''N''-methyltryptamine]] (NMT).<ref name="DeleuHanssens2000" />

The experimental [[partition coefficient|log P]] of frovatriptan is 0.9 and its predicted log P is 1.2.<ref name="PubChem">{{cite web | title=Frovatriptan | website=PubChem | url=https://pubchem.ncbi.nlm.nih.gov/compound/77992 | access-date=29 July 2025}}</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">{{cite journal | vauthors = Parsons AA, Parker SG, Raval P, Campbell CA, Lewis VA, Griffiths R, Hunter AJ, Hamilton TC, King FD | title = Comparison of the cardiovascular effects of the novel 5-HT(1B/1D) receptor agonist, SB 209509 (VML251), and sumatriptan in dogs | journal = J Cardiovasc Pharmacol | volume = 30 | issue = 1 | pages = 136–141 | date = July 1997 | pmid = 9268233 | doi = 10.1097/00005344-199707000-00020 | url = }}</ref><ref name="ParsonsRavalSmith1998">{{cite journal | vauthors = Parsons AA, Raval P, Smith S, Tilford N, King FD, Kaumann AJ, Hunter J | title = Effects of the novel high-affinity 5-HT(1B/1D)-receptor ligand frovatriptan in human isolated basilar and coronary arteries | journal = J Cardiovasc Pharmacol | volume = 32 | issue = 2 | pages = 220–224 | date = August 1998 | pmid = 9700983 | doi = 10.1097/00005344-199808000-00008 | url = }}</ref> It was approved for medical use in the [[United States]] in 2001.<ref name="FDA2001">{{cite web | title=Drug Approval Package: Frova (Frovatriptan) NDA #21-006 | website=accessdata.fda.gov | date=20 November 2001 | url=https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-006_Frova.cfm | access-date=28 July 2025}}</ref>

==Society and culture==
===Legal status===
Frovatriptan is available only by [[Medical prescription|prescription]] in the United States and Canada.<ref>{{cite web|title=Patient Information Sheet -- Frovatriptan succinate (marketed as Frova) |url=https://www.fda.gov/cder/drug/InfoSheets/patient/frovatripanPIS.htm |date=July 2006 |publisher=Food and Drug Administration |access-date=2007-11-28 |archive-url=https://web.archive.org/web/20070929141557/https://www.fda.gov/cder/drug/InfoSheets/patient/frovatripanPIS.htm |archive-date=2007-09-29 |url-status=dead }}</ref>

==See also==
* [[Triptan]]
* [[Tetrahydrocarbazolamine]]
* [[LY-344864]]

==References==
{{Reflist}}

{{Antimigraine preparations}}
{{Serotonin receptor modulators}}
{{Tryptamines}}
{{Portal bar | Medicine}}
{{Authority control}}

[[Category:5-HT1B agonists]]
[[Category:5-HT1D agonists]]
[[Category:5-HT1F agonists]]
[[Category:5-HT7 agonists]]
[[Category:Carboxamides]]
[[Category:N-Monoalkyltryptamines]]
[[Category:Secondary amines]]
[[Category:Tetrahydrocarbazolamines]]
[[Category:Triptans]]

Frovatriptan - Revision history

imported>AlyInWikiWonderland: Wiki links, cat.