View source for Triptan

{{Short description|Class of pharmaceutical drugs}}
{{distinguish|text=[[Tryptan]] (the trade name of amino acid tryptophan) or the hydrocarbon [[triptane]] or [[Oxitriptan]]}}
{{Infobox drug class
| Name             = Triptans
| Image            = Sumatriptan.svg
| Width            = 225px
| ImageClass       = skin-invert-image
| Caption          = [[Chemical structure]] of [[sumatriptan]], the prototypical triptan
| Use              = [[Migraine]], [[cluster headache]]
| Biological_target= [[Serotonin]] [[5-HT1B receptor|5-HT<sub>1B</sub>]], [[5-HT1D receptor|5-HT<sub>1D</sub>]], and [[5-HT1F receptor|5-HT<sub>1F</sub> receptor]]s
| ATC_prefix       = N02CC
}}

'''Triptans''' are a family of [[antimigraine drug]]s used to [[abortive medication|abort]] [[migraine]]s and [[cluster headache]]s.<ref name="TepperRapoport1999">{{cite journal | title = The triptans - A summary | author1=Tepper S. J. |author2=Rapoport A. M. | journal = CNS Drugs | volume = 12 | issue = 5 | pages = 403–417 | year = 1999 | doi = 10.2165/00023210-199912050-00007 | s2cid=72149615 }}</ref> While effective at treating individual headaches, they do not provide [[prophylaxis|preventive]] treatment and are not [[cure|curative]]. They are not effective for the treatment of [[tension headache|tension–type headache]],<ref name="Mutschler">{{cite book|last=Mutschler|first=Ernst|author2=Gerd Geisslinger |author3=Heyo K. Kroemer |author4=Sabine Menzel |author5=Peter Ruth |title=Arzneimittelwirkungen|publisher=Wissenschaftliche Verlagsgesellschaft|location=Stuttgart|date=2013|edition=10|pages=233–4|isbn=978-3-8047-2898-1|language=de}}</ref> except in persons who also experience migraines.<ref name="Green 2015">{{Cite book|title=Headache and Migraine Biology and Management|last=Green|first=Mark W.|publisher=Academic Press|year=2015|isbn=978-0-12-800901-7|editor-last=Diamond|editor-first=Seymour|page=44|chapter=Overview of Migraine: Recognition, Diagnosis, and Pathophysiology|editor-last2=Cady|editor-first2=Roger K.|editor-last3=Diamond|editor-first3=Merle L.|editor-last4=Green|editor-first4=Mark W.|editor-last5=Martin|editor-first5=Vincent T.|chapter-url=https://books.google.com/books?id=h-acBAAAQBAJ&pg=PA44|via=GoogleBooks|url-status=live|archive-url=https://web.archive.org/web/20180506021431/https://books.google.com/books?id=h-acBAAAQBAJ&pg=PA44|archive-date=2018-05-06}}</ref> Triptans do not relieve other kinds of [[pain]]. They are taken [[oral administration|orally]] and by other [[route of administration|route]]s.

The drugs of this class act as [[agonists]] for [[serotonin]] [[5-HT1B receptor|5-HT<sub>1B</sub>]] and [[5-HT1D receptor|5-HT<sub>1D</sub> receptor]]s at blood vessels and nerve endings in the brain. Some also activate the [[5-HT1F receptor|5-HT<sub>1F</sub> receptor]]. Structurally, triptans are [[substituted tryptamine]]s or closely related to tryptamines, for instance the [[psychedelic drug]] [[dimethyltryptamine]] (DMT).

The first clinically available triptan was [[sumatriptan]], which has been marketed since 1991. Subsequently, a variety of other triptans have also been marketed, including [[zolmitriptan]], [[naratriptan]], [[rizatriptan]], [[almotriptan]], [[eletriptan]], and [[frovatriptan]]. Triptans have largely replaced [[ergoline]] drugs like [[ergotamine]] and [[dihydroergotamine]], an older class of medications used to relieve migraine and cluster headaches.<ref>{{Cite journal|last1=Antonaci|first1=Fabio|last2=Ghiotto|first2=Natascia|last3=Wu|first3=Shizheng|last4=Pucci|first4=Ennio|last5=Costa|first5=Alfredo|date=2016|title=Recent advances in migraine therapy|journal=SpringerPlus|volume=5|page=637|doi=10.1186/s40064-016-2211-8|issn=2193-1801|pmc=4870579|pmid=27330903 |doi-access=free }}</ref>

==Medical uses==
===Migraine===
Triptans are used for the treatment of severe migraine attacks or those that do not respond to [[NSAID]]s<ref name="pmid17405970">{{cite journal|vauthors=Brandes JL, Kudrow D, Stark SR, etal |title=Sumatriptan-naproxen for acute treatment of migraine: a randomized trial |journal=JAMA |volume=297 |issue=13 |pages=1443–1454 |year=2007 |pmid=17405970 |doi=10.1001/jama.297.13.1443|doi-access=free }}</ref> or other [[Over-the-counter drug|over-the-counter]] drugs.<ref name="pmid11112243">{{cite journal |vauthors=Lipton RB, Baggish JS, Stewart WF, Codispoti JR, Fu M |title=Efficacy and safety of acetaminophen in the treatment of migraine: results of a randomized, double-blind, placebo-controlled, population-based study |journal=Arch. Intern. Med. |volume=160 |issue=22 |pages=3486–92 |year=2000 |pmid=11112243 |doi=10.1001/archinte.160.22.3486|doi-access=free }}</ref> Triptans are a mid-line treatment suitable for many migraineurs with typical attacks. They may not work for atypical or unusually severe migraine attacks, transformed migraine, or status migrainosus (continuous migraine).

Triptans are highly effective, reducing the symptoms or aborting the attack within 30 to 90 minutes in 70–80% of patients.<ref>{{Cite journal |last1=Sonal Sekhar |first1=M. |last2=Sasidharan |first2=Shalini |last3=Joseph |first3=Siby |last4=Kumar |first4=Anand |date=January 1, 2012 |title=Migraine management: How do the adult and paediatric migraines differ? |journal=Saudi Pharmaceutical Journal |volume=20 |issue=1 |pages=1–7 |doi=10.1016/j.jsps.2011.07.001 |issn=1319-0164 |pmc=3745030 |pmid=23960771}}</ref> A 2024 [[systematic review]] and [[Meta-analysis|network meta analysis]] compared the effectiveness of medications for acute migraine attacks in adults. It found that triptans were the most effective class of drugs followed by non-steroidal anti-inflammatories.<ref>{{Cite journal |last=Karlsson |first=William K. |last2=Ostinelli |first2=Edoardo G. |last3=Zhuang |first3=Zixuan A. |last4=Kokoti |first4=Lili |last5=Christensen |first5=Rune H. |last6=Al-Khazali |first6=Haidar M. |last7=Deligianni |first7=Christina I. |last8=Tomlinson |first8=Anneka |last9=Ashina |first9=Håkan |last10=Torre |first10=Elena Ruiz de la |last11=Diener |first11=Hans-Christoph |last12=Cipriani |first12=Andrea |last13=Ashina |first13=Messoud |date=2024-09-18 |title=Comparative effects of drug interventions for the acute management of migraine episodes in adults: systematic review and network meta-analysis |url=https://www.bmj.com/content/386/bmj-2024-080107 |journal=BMJ |language=en |volume=386 |article-number=e080107 |doi=10.1136/bmj-2024-080107 |issn=1756-1833 |pmid=39293828|pmc=11409395 }}</ref><ref>{{Cite journal |date=4 April 2025 |title=Which drugs are best for migraine attacks? |url=https://evidence.nihr.ac.uk/alert/which-drugs-are-best-for-migraine-attacks/ |journal=NIHR Evidence}}</ref> 

A test measuring a person's skin [[Allodynia|sensitivity]] during a migraine may indicate whether the individual will respond to treatment with triptans.<ref>{{cite journal|year=2004|title=Defeating migraine pain with triptans: A race against the development of cutaneous allodynia|journal=Annals of Neurology|volume=55|issue=1|pages=19–26|pmid=14705108|doi=10.1002/ana.10786|last1=Burstein|first1=R|last2=Collins|first2=B|last3=Jakubowski|first3=M|s2cid=24040813}}</ref>  Triptans are most effective in those with no skin sensitivity; with skin sensitivity, it is best to take triptans within twenty minutes of the headache's onset.<ref>{{Cite journal |last2= Jakubowski|first2= Moshe|last3= Rauch|first3= Steven D.|date=2011 |title=The science of migraine |journal=Journal of Vestibular Research: Equilibrium & Orientation |volume=21 |issue=6 |pages=305–314 |doi=10.3233/VES-2012-0433 |issn=0957-4271 |pmc=3690498 |pmid=22348935|last1= Burstein|first1= Rami}}</ref>

Oral [[rizatriptan]] and nasal [[zolmitriptan]] are the most used triptans for migraines in children.<ref>{{cite journal|year=2010|title=The use of triptans for pediatric migraines|journal=Paediatr Drugs|volume=12|issue=6|pages=379–389|pmid=21028917|last1=Eiland|first1=L. S.|last2=Hunt|first2=M. O.|s2cid=11187764|doi=10.2165/11532860-000000000-00000}}</ref>

====Correct timing of intake====
Triptans should be taken as soon as possible after the onset of pain. In case of migraine with [[Aura (migraine)|aura]] they are to be taken after the aura and with the onset of pain.<ref name="AC" /> If taken too early, they may not have the full effect on symptom reduction, and in case of an aura, they can worsen the aura. It is assumed that blood vessels are [[Vasoconstriction|constricted]] during the aura phase and [[Vasodilation|dilated]] during the pain phase, so a constrictive medication like a triptan is not recommended during the aura.<ref>{{Cite journal |last2= Elliott|first2= D.|date=June 6, 2007 |title=Acute migraine: Current treatment and emerging therapies |journal=Therapeutics and Clinical Risk Management |volume=3 |issue=3 |pages=449–459 |issn=1176-6336 |pmc=2386351 |pmid=18488069|last1= Kalra|first1= A. A.}}</ref>

===Cluster headache===
Triptans are effective for the treatment of [[cluster headache]]. This has been demonstrated for [[Subcutaneous injection|subcutaneous]] sumatriptan and [[intranasal]] zolmitriptan, the former of which is more effective according to a 2013 [[Cochrane review]]. Tablets were not considered appropriate in this review.<ref>{{cite journal|title=Triptans for acute cluster headache|journal=The Cochrane Database of Systematic Reviews|volume=7|issue=7|article-number=CD008042|pmid=24353996|doi=10.1002/14651858.CD008042.pub3|year=2013|last1=Law|first1=S|last2=Derry|first2=S|last3=Moore|first3=R. A.|pmc=4170909}}</ref>

===Altitude sickness===
A single [[randomized controlled trial]] found that sumatriptan may be able to prevent [[altitude sickness]].<ref name="pmid17557349">{{cite journal |vauthors=Jafarian S, Gorouhi F, Salimi S, Lotfi J |title=Sumatriptan for prevention of acute mountain sickness: randomized clinical trial |journal=Ann. Neurol. |volume=62 |issue=3 |pages=273–7 |year=2007 |pmid=17557349 |doi=10.1002/ana.21162|s2cid=7799716 }}</ref>

===Available forms===
All marketed triptans are available in [[oral administration|oral]] form; some in form of [[sublingual]] tablets.<ref name="AC">{{cite book|title=Austria-Codex|at=Zomig Rapimelt; Maxalt Rapitab|editor=Haberfeld, H|publisher=Österreichischer Apothekerverlag|location=Vienna|year=2016|language=de}}</ref> [[Sumatriptan]] and [[zolmitriptan]] are also available as [[nasal spray]]s.<ref name="AC" /><ref>{{Cite web|url=https://www.gsksource.com/pharma/content/dam/GlaxoSmithKline/US/en/Prescribing_Information/Imitrex_Nasal_Spray/pdf/IMITREX-NASAL-SPRAY-PI-PIL.PDF|title=Imitrex Nasal Spray package insert|website=GlaxoSmithKline prescribing information|access-date=May 20, 2016|url-status=live|archive-url=https://web.archive.org/web/20150905173656/https://www.gsksource.com/pharma/content/dam/GlaxoSmithKline/US/en/Prescribing_Information/Imitrex_Nasal_Spray/pdf/IMITREX-NASAL-SPRAY-PI-PIL.PDF|archive-date=September 5, 2015}}</ref> For sumatriptan, a number of other application forms are marketed: [[suppositories]], a subcutaneous injection,<ref name="AC" /> an [[iontophoretic]] transdermal patch, which uses low voltage controlled by a pre-programmed microchip to deliver a single dose of sumatriptan through the skin within 30 minutes;<ref name=":0">{{Cite journal|last1=Pierce|first1=Mark|last2=Marbury|first2=Thomas|last3=O'Neill|first3=Carol|last4=Siegel|first4=Steven|last5=Du|first5=Wei|last6=Sebree|first6=Terri|date=2009-06-01|title=Zelrix: a novel transdermal formulation of sumatriptan|journal=Headache|volume=49|issue=6|pages=817–825|doi=10.1111/j.1526-4610.2009.01437.x|issn=1526-4610|pmid=19438727|doi-access=free}}</ref> a drug-device combination containing sumatriptan powder that is "breath powered" allowing the user to blow sumatriptan powder in to their nostrils;<ref>{{Cite web|url=https://www.pharmacytimes.com/news/onzetra-xsail-approved-as-migraine-treatment|title=Onzetra Xsail Approved as Migraine Treatment|date=February 3, 2016|website=pharmacytimes.com|access-date=October 1, 2019}}</ref> as well as a needle-free injection system that works with air pressure.<ref name="Zogenix" />

{| class="wikitable"
|+ Formulations<ref>{{Cite journal|last=Gladstone|first=Jonathan|title=Newer formulations of the triptans: advances in migraine management|journal=Drugs|year=2003 |volume=63|issue=21 |pages=2285–2505|doi=10.2165/00003495-200363210-00002 |pmid=14524731 |s2cid=46971222 |via=2305}}</ref>
! Tablet
! Oral disintegrating tablets
! Nasal spray
! Subcutaneous injection
! Rectal suppository
|-
| all triptans
| [[rizatriptan]]
| [[sumatriptan]]
| [[sumatriptan]]
| [[sumatriptan]]
|-
|
| [[zolmitriptan]]
| [[zolmitriptan]]
|
|
|}

==Contraindications==
All triptans are [[contraindication|contraindicated]] in patients with [[cardiovascular disease]]s ([[coronary spasm]]s, symptomatic [[coronary artery disease]], after a [[heart attack]] or [[stroke]], uncontrolled [[hypertension]], [[Raynaud's disease]], [[peripheral artery disease]]).<ref>{{cite journal |last1=Dodick |first1=David W. |last2=Shewale |first2=Anand S. |last3=Lipton |first3=Richard B. |last4=Baum |first4=Seth J. |last5=Marcus |first5=Steven C. |last6=Silberstein |first6=Stephen D. |last7=Pavlovic |first7=Jelena M. |last8=Bennett |first8=Nathan L. |last9=Young |first9=William B. |last10=Viswanathan |first10=Hema N. |last11=Doshi |first11=Jalpa A. |last12=Weintraub |first12=Howard |title=Migraine Patients With Cardiovascular Disease and Contraindications: An Analysis of Real-World Claims Data |journal=Journal of Primary Care & Community Health |date=January 2020 |volume=11 |doi=10.1177/2150132720963680 |pmid=33095099 |pmc=7585888 }}</ref><ref>{{cite journal |last1=Tepper |first1=Stewart J. |last2=Spears |first2=Roderick C. |title=Acute Treatment of Migraine |journal=Neurologic Clinics |date=May 2009 |volume=27 |issue=2 |pages=417–427 |doi=10.1016/j.ncl.2008.11.008 |pmid=19289223 }}</ref> Most triptans are also contraindicated during pregnancy and breastfeeding and for patients younger than 18; but sumatriptan and zolmitriptan nasal sprays are also approved for youths over 12.<ref name="Mutschler" /> In spite of expert opinion and evidence to the contrary, the FDA and some other drug governance bodies have stated that [[monoamine oxidase inhibitor]]s are contraindicated for sumatriptan, zolmitriptan and rizatriptan,<ref name="Ferrari" /><ref name="Goodman" /> and combination with [[ergot alkaloid]]s such as [[ergotamine]] for all substances.<ref name="AC" />

At least two triptans (sumatriptan and rizatriptan) have been listed under the unacceptable medication by the [[Canadian Blood Services]] as a potential risk to the recipient; hence, donors are required not to have taken the medication for the last 72 hours.<ref>{{Cite journal |last1=Gawde |first1=Prathamesh |last2=Shah |first2=Harsh |last3=Patel |first3=Harsh |last4=Bharathi |first4=Koppineedi S |last5=Patel |first5=Neil |last6=Sethi |first6=Yashendra |last7=Kaka |first7=Nirja |title=Revisiting Migraine: The Evolving Pathophysiology and the Expanding Management Armamentarium |journal=Cureus |date=2023 |volume=15 |issue=2 |article-number=e34553 |doi=10.7759/cureus.34553 |doi-access=free |issn=2168-8184 |pmc=9985459 |pmid=36879707}}</ref>

==Adverse effects==
Triptans have few side effects if used in correct dosage and frequency. The most common adverse effect is recurrence of migraine. A [[systematic review]] found that "rizatriptan 10 mg was the only triptan with a recurrence rate [the reappearance of moderate to severe pain within 24 hours after the response at 2 hours] greater than that of placebo".<ref name="pmid17883520">{{cite journal |vauthors=Pascual J, Mateos V, Roig C, Sanchez-Del-Rio M, Jiménez D |title=Marketed oral triptans in the acute treatment of migraine: a systematic review on efficacy and tolerability |journal=Headache |volume=47 |issue=8 |pages=1152–68 |year=2007 |pmid=17883520 |doi=10.1111/j.1526-4610.2007.00849.x|doi-access=free }}</ref>

There is a theoretical risk of coronary spasm in patients with established heart disease, and cardiac events after taking triptans may rarely occur.<ref name="pmid9827245">{{cite journal |vauthors=Dahlöf CG, Mathew N |title=Cardiovascular safety of 5HT1B/1D agonists--is there a cause for concern? |journal=Cephalalgia: An International Journal of Headache |volume=18 |issue=8 |pages=539–45 |year=1998 |pmid=9827245 |doi=10.1046/j.1468-2982.1998.1808539.x|s2cid=30125923 }}</ref>

==Interactions==
Combination of triptans with other serotonergic drugs such as ergot alkaloids, monoamine oxidase inhibitors, [[selective serotonin reuptake inhibitor]]s (SSRIs), [[serotonin–norepinephrine reuptake inhibitor]]s (SNRIs) or [[St John's wort]] has been alleged to induce symptoms of a [[serotonin syndrome]] (a syndrome of changes in mental status, autonomic instability, neuromuscular abnormalities, and gastrointestinal symptoms),<ref name="Mutschler" /><ref name="AC" /> whereas scientific studies indicate there is no potential for life-threatening serotonin syndrome in patients taking triptans and SSRI or SNRIs at the same time, although the FDA has officially stated otherwise.<ref name="Rolan 2012 pp. 949–957">{{cite journal | last=Rolan | first=Paul E. | title=Drug Interactions with Triptans | journal=CNS Drugs | publisher=Springer Science and Business Media LLC | volume=26 | issue=11 | date=2012-09-25 | issn=1172-7047 | pmid=23018546 | doi=10.1007/s40263-012-0002-5 | pages=949–957| s2cid=43699741 }}</ref><ref>{{cite journal|title=The Serotonin Syndrome, Triptans, and the Potential for Drug–Drug Interactions|journal=Headache: The Journal of Head and Face Pain|volume=47|issue=2|pages=266–9|doi=10.1111/j.1526-4610.2006.00691.x|pmid=17300366|year=2007|last1=Shapiro|first1=Robert E.|last2=Tepper|first2=Stewart J.|s2cid=21075435}}</ref><ref>{{cite journal|title=The FDA Alert on Serotonin Syndrome With Use of Triptans Combined With Selective Serotonin Reuptake Inhibitors or Selective Serotonin-Norepinephrine Reuptake Inhibitors: American Headache Society Position Paper|journal=Headache: The Journal of Head and Face Pain|volume=50|issue=6|pages=1089–99|doi=10.1111/j.1526-4610.2010.01691.x|pmid=20618823|year=2010|last1=Evans|first1=Randolph W.|last2=Tepper|first2=Stewart J.|last3=Shapiro|first3=Robert E.|last4=Sun-Edelstein|first4=Christina|last5=Tietjen|first5=Gretchen E.|s2cid=40713435|doi-access=free}}</ref><ref>{{cite journal|title=Triptans, serotonin agonists, and serotonin syndrome (serotonin toxicity): a review|last1=Gillman|journal=Headache|volume=50|issue=2|year=2010|pages=264–272|doi=10.1111/j.1526-4610.2009.01575.x|pmid=19925619|s2cid=221752556 |doi-access=free}}</ref><ref>{{cite journal|title=The FDA alert on serotonin syndrome with combined use of SSRIs or SNRIs and triptans: an analysis of the 29 case reports|    journal=MedGenMed|    volume=9|    issue=3|    page=48|    pmid=18092054|    pmc=2100123|    year=2007|    last1=Evans|    first1=R. W.}}</ref><ref>{{cite journal|title=Serotonin syndrome risks when combining SSRI/SNRI drugs and triptans: is the FDA's alert warranted?|journal=Annals of Pharmacotherapy|volume=42|issue=11|pages=1692–6|pmid=18957623|year=2008|last1=Wenzel|first1=R. G.|last2=Tepper|first2=S|last3=Korab|first3=W. E.|last4=Freitag|first4=F|doi=10.1345/aph.1L260|s2cid=24942783}}</ref><ref name="FDA ALERT [7/2006]:">{{cite web|url=https://www.fda.gov/CDER/Drug/InfoSheets/HCP/venlafaxineHCP.htm|title=Information for Healthcare Professionals|last=US Food and Drug Administration|date=2006-07-19|publisher=[[Food and Drug Administration]]|access-date=2008-01-10|archive-url=https://web.archive.org/web/20080219184710/https://www.fda.gov/CDER/Drug/InfoSheets/HCP/venlafaxineHCP.htm <!-- Bot retrieved archive -->|archive-date=2008-02-19}}</ref> Combining triptans with ergot alkaloids is contraindicated because of the danger of coronary spasms.<ref name="AC" />

In a study from [[Harvard Medical School]] and the [[University of Florida College of Medicine]] involving 47,968 patients and published on 26 February 2018, concomitant use of a [[selective serotonin reuptake inhibitor]] or [[selective norepinephrine reuptake inhibitor]] for [[Major depressive disorder|depression]] with a triptan for [[migraine]] did not demonstrate an increased risk of the [[serotonin syndrome]].<ref>{{cite journal|title=Association of Coprescription of Triptan Antimigraine Drugs and Selective Serotonin Reuptake Inhibitor or Selective Norepinephrine Reuptake Inhibitor Antidepressants With Serotonin Syndrome |first1=Yulia|last1=Orlova|first2=Paul|last2=Rizzoli|first3=Elizabeth|last3=Loder|date=26 February 2018|journal=JAMA Neurology|volume=75|issue=5|pages=566–572|pmid=29482205|doi=10.1001/jamaneurol.2017.5144|pmc=5885255}}</ref>

[[Pharmacokinetic]] interactions (for example, mediated by [[cytochrome P450|CYP]] liver enzymes or [[transporter protein]]s) are different for the individual substances; for most triptans, they are mild to absent. Eletriptan blood plasma levels are increased by strong inhibitors of [[CYP3A4]], and frovatriptan levels by [[CYP1A2]] inhibitors such as [[fluvoxamine]].<ref name="AC" />

==Pharmacology==
===Mechanism of action===
{{Further|Discovery and development of triptans|Serotonin receptor agonist}}

Their action is attributed to their [[receptor agonist|agonist]]<ref name="Tepper">{{Cite journal | last1 = Tepper | first1 = S. J. | last2 = Rapoport | first2 = A. M. | last3 = Sheftell | first3 = F. D. | title = Mechanisms of action of the 5-HT1B/1D receptor agonists | journal = Archives of Neurology | volume = 59 | issue = 7 | pages = 1084–1088 | year = 2002 | pmid = 12117355 | doi=10.1001/archneur.59.7.1084 | doi-access = free }}</ref> effects on [[serotonin]] [[5-HT1B receptor|5-HT<sub>1B</sub>]] and [[5-HT1D receptor|5-HT<sub>1D</sub> receptors]] in blood vessels (causing their [[vasoconstriction|constriction]]) and nerve endings in the brain, and subsequent inhibition of pro-inflammatory [[neuropeptide]] release, including [[CGRP]] and [[substance P]]. Triptans are [[Ligand (biochemistry)#Receptor.2Fligand binding affinity|selective]] agents for 5-HT<sub>1B</sub> and 5-HT<sub>1D</sub><ref name="Tepper" /> and have low or even no [[Ligand (biochemistry)#Receptor.2Fligand binding affinity|affinity]] for other types of 5-HT receptors.<ref name="Goodman">{{cite book|author=Brunton, L. |author2=Lazo, J. |author3=Parker, K. |year=2006|title=Goodman & Gilman's The Pharmacological Basis of Therapeutics|edition=11th|publisher=McGraw-Hill Education|pages=305–308}}</ref>

5-HT receptors are classified into seven different families named 5-HT<sub>1</sub> to 5-HT<sub>7</sub>. All receptors are [[G protein coupled receptors]] with seven transmembrane domains with the one exception of  5-HT<sub>3</sub> receptor which is a [[ligand gated ion channel]]. There is a high [[homology (biology)|homology]] in the amino acid sequence within each family. Each family couples to the same [[second messenger systems]]. Subtypes of 5-HT<sub>1</sub> are the 5-HT<sub>1A</sub>, 5-HT<sub>1B</sub>, 5-HT<sub>1D</sub>, 5-HT<sub>1E</sub> and 5-HT<sub>1F</sub> receptors. All 5-HT<sub>1D</sub> receptors are coupled to inhibition of [[adenylate cyclase]]. 5-HT<sub>1B</sub> and 5-HT<sub>1D</sub> receptors have been difficult to distinguish on a pharmacological basis. After cloning two distinct genes for 5-HT<sub>1B</sub> and 5-HT<sub>1D</sub> receptors, a better insight into distribution and expression in different tissues was gained, except in brain tissue where they are overlapping in several areas.<ref name="Hamel, E. 1999">{{cite journal|author=Hamel, E.|year=1999|title=The biology of serotonin receptors: focus on migraine pathophysiology and treatment|journal=Can J Neurol Sci|at=26 Suppl 3:S2–6|pmid=10563226|volume=26 Suppl 3|issue=3|doi=10.1017/s0317167100000123|doi-access=free}}</ref>

Most [[mammalian]] species, including humans, have 5-HT<sub>1D</sub> binding sites widely distributed throughout the [[central nervous system]]. 5-HT<sub>1D</sub> receptors are found in all areas of the brain but they differ in quantity at each area.<ref name="Lowther">{{cite journal|title=The distribution of 5HT<sub>1D</sub> and 5HT<sub>1E</sub> binding sites in human brain|author=Lowther, S.|journal=Eur J Pharmacol|year=1992|volume=222|issue=1|pages=137–42|pmid=1468490|doi=10.1016/0014-2999(92)90473-h}}</ref>
An important initiator of head pain is suggested to be the activation of [[trigeminovascular]] [[Afferent nerve fiber|afferent]] nerves which upon activation releases neuropeptides such as CGRP, substance P and [[neurokinin A]]. Also they are thought to promote neurogenic inflammatory response important for sensitization of [[sensory neuron|sensory]] afferents, and also transmission and generation of head pain centrally. 5-HT<sub>1D</sub> has been found responsible for inhibition of neurogenic inflammation upon administration with sumatriptan and other related compounds that act on prejunctional 5-HT<sub>1D</sub> receptors.<ref name="Hamel, E. 1999" />

All triptans, like the older drug [[dihydroergotamine]], have agonistic effects on the 5-HT<sub>1D</sub> receptor. Comparison of sumatriptan and dihydroergotamine showed that dihydroergotamine has high affinity and sumatriptan has medium affinity for 5-HT<sub>1D</sub>.<ref name="Tepper" />  Triptans have at least three modes of action. These antimigraine mechanisms are:

# [[vasoconstriction]] of pain producing intra cranial extracerebral vessels by a direct effect on vascular smooth muscle. Sumatriptan and rizatriptan have been shown to cause vasoconstriction in the human [[middle meningeal arteries]].
# inhibition of vasoactive neuropeptide release by trigeminal terminals innervating intracranial vessels and the dura mater. The trigeminocervical complex has 5-HT<sub>1D</sub> receptors that bind dihydroergotamine and triptans in humans. Rizatriptan has been shown to block dural vasodilation and plasma protein extravasation by inhibiting the release of CGRP via activation of receptors on preganglionic trigeminal sensory nerver terminals. Sumatriptan is shown to inhibit potassium stimulated CGRP secretion from cultured trigeminal neurons in a dose dependant manner and may also inhibit the release of substance P.
# inhibition of [[nociceptive]] [[neurotransmission]] within the trigeminocervical complex in the [[brainstem]] and upper cervical spinal column. Rizatriptan has central trigeminal antinociceptive activity.
Other possibilities of triptans in antimigraine effects are modulation of [[nitric oxide]] dependent [[signal transduction pathways]], nitric oxide scavenging in the brain, and sodium dependent cell metabolic activity.<ref>{{cite journal | last1 = Goadsby | first1 = P. J. | year = 1998 | title = Serotonin 5HT<sub>1B/1D</sub> receptor agonists in migraine - Comparative pharmacology and its therapeutic implications | journal = CNS Drugs | volume = 10 | issue = 4| pages = 271–286 | doi = 10.2165/00023210-199810040-00005 | s2cid = 68150076 }}</ref><ref name="Tepper" />

Most of the triptans, for instance [[sumatriptan]], [[zolmitriptan]], and others, are inactive as serotonin [[5-HT2A receptor|5-HT<sub>2A</sub> receptor]] [[agonist]]s.<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-HT<sub>1F</sub> 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> However, a few triptans, including [[donitriptan]], [[avitriptan]], and [[eletriptan]], have been found to act as serotonin 5-HT<sub>2A</sub> receptor agonists, albeit with one to three orders of magnitude lower activational potency than at the serotonin 5-HT<sub>1B</sub> and 5-HT<sub>1D</sub> receptors.<ref name="Rubio-BeltránLabastida-RamírezHaanes2019" />

===Pharmacokinetics===
Triptans have a wide variety of [[pharmacokinetic]] properties. [[Bioavailability]] is between 14% and 70%, [[biological half-life]] (T<sub>1/2</sub>) is between 2 and 26 hours. Their good ability to cross the [[blood–brain barrier]] and the rather long half-life of some triptans may result in lower frequencies of migraine recurrence.<ref name="Goodman" /><ref name="Bigal">{{cite journal | last1 = Bigal | first1 = M. E. | last2 = Bordini | first2 = C. A. | last3 = Antoniazzi | first3 = A. L. | last4 = Speciali | first4 = J. G. | year = 2003 | title = The triptan formulations: a critical evaluation | journal = Arquivos de Neuro-Psiquiatria | volume = 61 | issue = 2A | pages = 313–320 | doi = 10.1590/s0004-282x2003000200032 | pmid = 12806521 | doi-access = free }}</ref><ref name="Armstrong">{{cite journal | last1 = Armstrong | first1 = S. C. | last2 = Cozza | first2 = K. L. | year = 2002 | title = Triptans | journal = Psychosomatics | volume = 43 | issue = 6| pages = 502–504 | doi = 10.1176/appi.psy.43.6.502 | pmid=12444236| doi-access = free }}</ref><ref name="Mathew">{{cite journal | last1 = Mathew | first1 = N. T. | last2 = Loder | first2 = E. W. | year = 2005 | title = Evaluating the triptans | doi = 10.1016/j.amjmed.2005.01.017 | pmid = 15841885 | journal = The American Journal of Medicine Supplements | volume = 118 | issue = 1| pages = 28–35 }}</ref>

===Comparison===
{| class="wikitable" style="margin: 1em auto 1em auto; font-size: small;"
|+ Comparative pharmacology of marketed triptans in their oral formulations<ref name="Goodman" /><ref name="Bigal"/><ref name="Armstrong"/><ref name="Mathew"/><ref name="Deleu">{{cite journal|title=Current and emerging second-generation triptans in acute migraine therapy: a comparative review|journal=J Clin Pharmacol|author1=Deleu, D. |author2=Hanssens Y. |year=2000|volume=40|issue=7|pages=687–700|pmid=10883409|doi=10.1177/00912700022009431|s2cid=15585554}}</ref><ref name="TekesSzegiHashemi2013">{{cite journal | vauthors = Tekes K, Szegi P, Hashemi F, Laufer R, Kalász H, Siddiq A, Ertsey C | title = Medicinal chemistry of antimigraine drugs | journal = Curr Med Chem | volume = 20 | issue = 26 | pages = 3300–3316 | date = 2013 | pmid = 23746273 | doi = 10.2174/0929867311320260012 | 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-HT<sub>1F</sub> 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>
|-
! [[Drug]] !! [[Brand name|Brand]] !! [[Pharmaceutical company|Company]] !! [[Biological target|Target]]s !! [[5-HT1D receptor|5-HT<sub>1D</sub>]]<br />[[affinity (pharmacology)|affinity]] (K<sub>i</sub>) !! {{Abbrlink|F|Bioavailability}} !! [[log P]] !! [[log D]]<br /><small>(at [[pH]] 7.4)</small> !! [[Time to peak concentrations|T<sub>max</sub>]] !! [[Elimination half-life|T<sub>1/2</sub>]] !! [[Drug metabolism|Metabolism]] !! [[Dose (biochemistry)|Dose]]
|-
| [[Sumatriptan]] 
| align="center"| Imitrex
| align="center"| {{Abbrlink|GSK|Glaxo Smith Kline}}
| align="center"| 5-HT<sub>1B/D</sub>
| align="center"| 3.2–13{{nbsp}}nM
| align="center"| 14–17%
| align="center"| 0.8
| align="center"| –1.3
| align="center"| 2–2.5{{nbsp}}h
| align="center"| 2.5{{nbsp}}h
| align="center"| [[MAO-A]]
| align="center"| 25, 50, 100{{nbsp}}mg
|-
| [[Zolmitriptan]] 
| align="center"| Zomig
| align="center"| Grünenthal<ref>{{Cite web|url=https://www.astrazeneca.com/media-centre/press-releases/2017/astrazeneca-enters-agreement-with-grunenthal-to-divest-rights-to-migraine-treatment-zomig-07062017.html|title=AstraZeneca enters agreement with Grünenthal to divest rights to migraine treatment Zomig|website=www.astrazeneca.com|date=7 June 2017 |language=en|access-date=2018-03-22|url-status=live|archive-url=https://web.archive.org/web/20180322204845/https://www.astrazeneca.com/media-centre/press-releases/2017/astrazeneca-enters-agreement-with-grunenthal-to-divest-rights-to-migraine-treatment-zomig-07062017.html|archive-date=2018-03-22}}</ref>
| align="center"| 5-HT<sub>1B/D</sub>
| align="center"| 0.63{{nbsp}}nM
| align="center"| 40%
| align="center"| 1.6
| align="center"| –0.7
| align="center"| 1.5–2{{nbsp}}h
| align="center"| 2–3{{nbsp}}h
| align="center"| [[MAO-A]] <br /> [[CYP1A2]]
| align="center"| 2.5, 5{{nbsp}}mg
|-
| [[Naratriptan]] 
| align="center"| Amerge
| align="center"| {{Abbrlink|GSK|Glaxo Smith Kline}}
| align="center"| 5-HT<sub>1B/D</sub>
| align="center"| 5.0{{nbsp}}nM
| align="center"| 70%
| align="center"| 2.2
| align="center"| –0.2
| align="center"| 2–3{{nbsp}}h
| align="center"| 6{{nbsp}}h
| align="center"| Many CYPs <br /> [[MAO-A]]
| align="center"| 1, 2.5{{nbsp}}mg
|-
| [[Rizatriptan]] 
| align="center"| Maxalt
| align="center"| Merck
| align="center"| 5-HT<sub>1B/D</sub>
| align="center"| 20{{nbsp}}nM
| align="center"| 45%
| align="center"| 1.4
| align="center"| –0.7
| align="center"| 1–1.5{{nbsp}}h
| align="center"| 2–2.5{{nbsp}}h
| align="center"| [[MAO-A]]
| align="center"| 5, 10{{nbsp}}mg
|-
| [[Almotriptan]] 
| align="center"| Axert
| align="center"| Almirall-<br />Prodesfarma
| align="center"| 5-HT<sub>1B/D</sub> <br /> 5-HT<sub>1F</sub>
| align="center"| 16{{nbsp}}nM
| align="center"| 70%
| align="center"| 1.6
| align="center"| +0.35
| align="center"| 2.5{{nbsp}}h
| align="center"| 3.6{{nbsp}}h
| align="center"| [[CYP2D6]] <br /> [[CYP3A4]] <br /> [[MAO-A]]
| align="center"| 6.25, 12.5{{nbsp}}mg
|-
| [[Eletriptan]] 
| align="center"| Relpax
| align="center"| [[Pfizer]]
| align="center"| 5-HT<sub>1B/D</sub> <br /> 5-HT<sub>1F</sub><ref name=relpax_spc>{{cite web | title= Relpax – 20 mg and 40 mg | url= http://emc.medicines.org.uk/emc/assets/c/html/DisplayDoc.asp?DocumentID=8195 | access-date= 2008-11-09 | url-status= live | archive-url= https://web.archive.org/web/20040620163458/http://emc.medicines.org.uk/emc/assets/c/html/displaydoc.asp?documentid=8195 | archive-date= 2004-06-20 }}</ref>
| align="center"| 1.3{{nbsp}}nM
| align="center"| 50%
| align="center"| 3.9
| align="center"| +0.5
| align="center"| 1–2{{nbsp}}h
| align="center"| 3.6–5.5{{nbsp}}h
| align="center"| [[CYP3A4]]
| align="center"| 20, 40, 80{{nbsp}}mg
|-
| [[Frovatriptan]]
| align="center"| Frova
| align="center"| Vernalis
| align="center"| 5-HT<sub>1B/D</sub>
| align="center"| 4.0{{nbsp}}nM
| align="center"| 24–30%
| align="center"| 0.9
| align="center"| –1.53
| align="center"| 2–4{{nbsp}}h
| align="center"| 26{{nbsp}}h
| align="center"| [[CYP1A2]]
| align="center"| 2.5{{nbsp}}mg
|}

Zolmitriptan is different from the other triptans because it is converted to an active ''N''-desmethyl metabolite which has higher affinity for the serotonin 5-HT<sub>1D</sub> and 5-HT<sub>1B</sub> receptors; both substances have a biological half-life of 2 to 3 hours.<ref name="Goodman" /> In studies, newer triptans are mostly compared to sumatriptan.<ref name="Ferrari">{{cite journal | last1 = Ferrari | first1 = M. D. | last2 = Goadsby | first2 = P. J. | last3 = Roon | first3 = K. I. | last4 = Lipton | first4 = R. B. | year = 2002 | title = Triptan (serotonin, 5-HT1D/1B agonists) in migraine: detailed results and methods of a meta-analysis of 53 trials | journal = Cephalalgia | volume = 22 | issue = 8| pages = 633–658 | doi = 10.1046/j.1468-2982.2002.00404.x | pmid=12383060| s2cid = 2368571 }}</ref> They are better than sumatriptan for their longer half-life in plasma and higher oral [[bioavailability]],<ref name="Foyes" /> but have a higher potential for [[central nervous]] side effects.<ref name="Mutschler" />

[[Donitriptan]] and [[avitriptan]] were never marketed.

==Chemistry==
{| class="wikitable floatright"
|+ Chemical structures of triptans
|-
| style="vertical-align:bottom" | [[File:Sumatriptan.svg|150px|class=skin-invert-image]]<br />[[sumatriptan]]
| style="vertical-align:bottom" | [[File:Rizatriptan.png|150px|class=skin-invert-image]]<br />[[rizatriptan]]
| style="vertical-align:bottom" | [[File:Naratriptan structure.svg|150px|class=skin-invert-image]]<br />[[naratriptan]]
|-
| style="vertical-align:bottom" | [[File:Eletriptan_skeletal.svg|150px|class=skin-invert-image]]<br />[[eletriptan]]
| style="vertical-align:bottom" | [[File:Donitriptan.svg|150px|class=skin-invert-image]]<br />[[donitriptan]]
| style="vertical-align:bottom" | [[File:Almotriptan_skeletal.svg|150px|class=skin-invert-image]]<br />[[almotriptan]]
|-
| style="vertical-align:bottom" | [[File:Frovatriptan structure.svg|150px|class=skin-invert-image]]<br />[[frovatriptan]]
| style="vertical-align:bottom" | [[File:Avitriptan.png|150px|class=skin-invert-image]]<br />[[avitriptan]]
| style="vertical-align:bottom" | [[File:Zolmitriptan.svg|150px|class=skin-invert-image]]<br />[[zolmitriptan]]
|-
| style="vertical-align:bottom" | [[File:LY334370.svg|150px|class=skin-invert-image]]<br />[[LY-334370]]
| style="vertical-align:bottom" | [[File:LY-344864.svg|150px|class=skin-invert-image]]<br />[[LY-344864]]
| style="vertical-align:bottom" | [[File:L 694 247.svg|150px|class=skin-invert-image]]<br />[[L-694247]]
|-
|}

Triptans are either [[substituted tryptamine|tryptamine]]s or closely related compounds.<ref name="Nancy2019">{{cite thesis | last=Nancy | first=Joy | author2=University of Canterbury | title=Molecular mimicry of anti-migraine drugs with neurotransmitters, dopamine (DA) &amp; serotonin (5-HT) and its role in the treatment of migraine. | publisher=University of Canterbury | date=2019 | doi=10.26021/8776 | url=https://ir.canterbury.ac.nz/handle/10092/17355 | access-date=29 July 2025 | page=}}</ref> Most triptans are simple tryptamines.<ref name="Nancy2019" /> These include [[sumatriptan]], [[rizatriptan]], [[donitriptan]], [[almotriptan]], [[zolmitriptan]], and [[L-694247]].<ref name="Nancy2019" /> Certain triptans, including [[eletriptan]], [[frovatriptan]], and [[LY-344864]], are [[cyclized tryptamine]]s.<ref name="Nancy2019" /> Other triptans, including [[naratriptan]], [[LY-334370]], and [[avitriptan]], are not technically tryptamines, although they are still closely related to tryptamines. Naratriptan and LY-334370 are [[piperidinylindole]]s rather than tryptamines, while avitriptan features a [[cyclic compound|cyclized]] [[propyl group|propyl]][[amine]] [[side chain]] instead of the [[ethyl group|ethyl]]amine side chain present in tryptamines. A number of triptans, including sumatriptan, rizatriptan, eletriptan, almotriptan, zolmitriptan, contain the [[psychedelic drug]] [[dimethyltryptamine]] (DMT) within their [[chemical structure]]s and hence are derivatives of DMT. Triptans may be thought of as [[synthetic compound|synthetic]] [[structural analog|analogue]]s of the [[monoamine neurotransmitter]] [[serotonin]] (5-hydroxytryptamine; 5-HT).<ref name="Nancy2019" />

==History==
{{Further|Discovery and development of triptans}}

The history of triptans began with the proposed existence of then unknown serotonin (5-hydroxytryptamine, 5-HT). In the late 1940s two groups of investigators, one in Italy and the other in the United States, identified a substance that was called ''serotonin'' in the US and ''enteramine'' in Italy. In the early 1950s it was confirmed that both substances were the same. In the mid-1950s it was proposed that serotonin had a role as a [[neurotransmitter]] in the central nervous system (CNS) of animals. Investigations of the mechanism of action were not very successful as experimental techniques were lacking.<ref name="Foyes">{{cite book|author=Lippincott, W. W. |author2=Lemke, T. L. |author3=Williams, D. A. |author4=Roche, V. F. |author5=Zito, S. W. |year=2013|title=Foye's Principles of Medicinal Chemistry|publisher=Lippincott Williams & Wilkins|pages=368–376}}</ref>

Later in the 1960s, studies showed that [[vasoconstriction]] caused by 5-HT, [[noradrenaline]] and [[ergotamine]] could reduce migraine attacks. Patrick P.A. Humphrey among others at [[Glaxo]] started researching the 5-HT receptor to discover a more direct 5-HT [[agonist]] with fewer side effects.

They continued developing and working on a desirable action on 5-HT by 5-HT<sub>1</sub> receptor activation for an anti-migraine drug. Continued work led to the [[Drug development|development]] of sumatriptan, now known as the first 5-HT<sub>1</sub> agonist, selective for the 5-HT<sub>1D/B</sub> receptors and also the 5-HT<sub>1F</sub> receptor with less affinity. By 1991 sumatriptan became available in clinical use in the Netherlands and in the US in 1993. However, there was always a debate about its mechanism of action, and it still remains unclear today. Later, Mike Moskowitz proposed a theory about "neuronal extravasation", and this was the first clue that sumatriptan might have a direct [[neuronal]] effect in migraine attacks.<ref>{{cite journal | last1 = Humphrey | first1 = P. P. | year = 2007 | title = The discovery of a new drug class for the acute treatment of migraine | doi = 10.1111/j.1526-4610.2007.00672.x | pmid = 17425704 | journal = Headache | volume = 47 | issue = Suppl 1| pages = S10–19 | s2cid = 12201740 | doi-access = free }}</ref>

Sumatriptan became a prototype for other triptans that have been developed for improved selectivity for the 5-HT<sub>1D/B</sub> receptors.<ref name="Foyes" />

==Society and culture==
===Legal status===
These drugs have been available only by prescription (US, Canada and UK), but sumatriptan became available over-the-counter in the UK in June 2006.<ref name="BBC_generic">{{cite web |publisher   = BBC News |date        = 2006-05-19 |title       = Pharmacies to sell migraine drug |url         = https://news.bbc.co.uk/2/hi/health/4996712.stm |access-date  = 2006-09-05 |url-status     = live |archive-url  = https://web.archive.org/web/20060924041401/http://news.bbc.co.uk/1/hi/health/4996712.stm |archive-date = 2006-09-24 }}</ref> The brand name of the OTC product in the UK is Imigran Recovery. The patent on Imitrex STATDose expired in December 2006, and injectable sumatriptan became available as a generic formula in August 2008.{{Citation needed|date=April 2010}} Sumavel Dosepro is a needle-free delivery of injectable sumatriptan that was approved in the US by the FDA in July 2009.<ref name="Zogenix">{{cite web|url=http://www.zogenix.com/index.php/news/sumavel-dosepro-sumatriptan-injection-approved-by-fda-for-acute-migraine-and-cluster-headache/|title=Zogenix, Inc. - Therapeutic Solutions for CNS Disorders and Rare Disease|website=www.zogenix.com|access-date=6 May 2018|url-status=live|archive-url=https://web.archive.org/web/20160821125219/http://www.zogenix.com/index.php/news/sumavel-dosepro-sumatriptan-injection-approved-by-fda-for-acute-migraine-and-cluster-headache/|archive-date=21 August 2016}}</ref> Sumatriptan became available as a generic in the US in late 2009. It used to be sold over-the-counter in Romania under the Imigran brand; however, as of August 2014 prescription is required. Zecuity, a sumatriptan transdermal patch, was approved by the US FDA in January 2013.<ref name=":0" /> The sumatriptan nasal powder was approved by the FDA in January 2016 and became available in the U.S. May 2016.<ref>{{Cite web|url=http://www.avanir.com/press/avanir-pharmaceuticals-announces-fda-approval-onzetra%E2%84%A2-xsail%E2%84%A2-avp-825-acute-treatment-migraine|title=Avanir's press release: FDA approves Onzetra|date=January 28, 2016|website=Avanir Pharmaceuticals|access-date=May 20, 2016|url-status=live|archive-url=https://web.archive.org/web/20160511232617/http://www.avanir.com/press/avanir-pharmaceuticals-announces-fda-approval-onzetra%E2%84%A2-xsail%E2%84%A2-avp-825-acute-treatment-migraine|archive-date=May 11, 2016}}</ref> [[Naratriptan]] is available OTC in Germany and Brazil.

==References==
{{Reflist}}

{{Antimigraine preparations}}
{{Serotonin receptor modulators}}
{{Tryptamines}}

[[Category:Triptans| ]]
[[Category:5-HT1B agonists]]
[[Category:5-HT1D agonists]]
[[Category:Sulfonamides]]