Editing Sumatriptan

{{Short description|Medication used for migraines & cluster headaches}}
{{Use American English|date=February 2018}}
{{Use dmy dates|date=October 2022}}
{{cs1 config|name-list-style=vanc|display-authors=6}}
{{Drugbox
| Watchedfields = changed
| verifiedrevid = 477173943
| IUPAC_name = 1-[3-(2-Dimethylaminoethyl)-1''H''-indol-5-yl]-''N''-methyl-methanesulfonamide
| image = Sumatriptan.svg
| alt = 
| image2 = Sumatriptan 3D ball-and-stick.png
| alt2 = Sumatriptan molecule

<!-- Clinical data -->| tradename = Imitrex, Imigran, others
| Drugs.com = {{drugs.com|monograph|sumatriptan}}
| DailyMedID = Sumatriptan
| routes_of_administration = [[By mouth]], [[subcutaneous injection|subcutaneous]], [[intranasal]], [[transdermal]]
| ATC_prefix = N02
| ATC_suffix = CC01

<!-- Legal status -->| legal_AU = <!-- S2, S3, S4, S5, S6, S7, S8, S9 or Unscheduled -->
| legal_AU_comment = 
| legal_BR = <!-- OTC, A1, A2, A3, B1, B2, C1, C2, C3, C4, C5, D1, D2, E, F -->
| legal_BR_comment = 
| legal_CA = Rx-only
| legal_CA_comment = 
| legal_DE = <!-- Anlage I, II, III or Unscheduled -->
| legal_DE_comment = 
| legal_NZ = <!-- Class A, B, C -->
| legal_NZ_comment = 
| legal_UK = POM
| legal_UK_comment = /&nbsp;P
| legal_US = Rx-only
| legal_US_comment = 
| legal_EU = 
| legal_EU_comment = 
| legal_UN = <!-- N I, II, III, IV / P I, II, III, IV -->
| legal_UN_comment = 
| legal_status = Rx-only

<!-- Pharmacokinetic data -->| bioavailability = 15% ([[oral administration|oral]]); 96% ([[subcutaneous injection|subcutaneous]])
| protein_bound = 14–21%
| metabolism = [[Monoamine oxidase]] (MAO)
| elimination_half-life = 2.5 hours
| excretion = 60% [[urine]]; 40% [[feces]]

<!-- Identifiers -->| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 103628-46-2
| PubChem = 5358
| IUPHAR_ligand = 54
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB00669
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 5165
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 8R78F6L9VO
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D00451
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 10650
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 128

<!-- Chemical data -->| C = 14
| H = 21
| N = 3
| O = 2
| S = 1
| smiles = O=S(=O)(NC)Cc1cc2c(cc1)[nH]cc2CCN(C)C
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C14H21N3O2S/c1-15-20(18,19)10-11-4-5-14-13(8-11)12(9-16-14)6-7-17(2)3/h4-5,8-9,15-16H,6-7,10H2,1-3H3
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = KQKPFRSPSRPDEB-UHFFFAOYSA-N
}}
<!-- Definition and medical uses -->

'''Sumatriptan''', sold under the brand name '''Imitrex''' among others, is a [[medication]] used to treat [[migraine headaches]] and [[cluster headaches]].<ref name=BNF76>{{cite book|title=British National Formulary: BNF 76|date=2018|publisher=Pharmaceutical Press|isbn=9780857113382|pages=474|edition=76}}</ref> It is taken [[Oral administration|orally]], [[Nasal administration|intranasally]], or by [[Subcutaneous injection|subcutaneous]] [[Injection under the skin|injection]].<ref name="AHFS2019">{{cite web |title=Sumatriptan Monograph for Professionals |url=https://www.drugs.com/monograph/sumatriptan.html |access-date=3 March 2019 |website=Drugs.com |publisher=American Society of Health-System Pharmacists}}</ref> Therapeutic effects generally occur within three hours.<ref name=AHFS2019/>

<!-- Side effects and mechanisms -->
Its primary effect as a serotonin [[5-HT1B|5-HT<sub>1B</sub>]]/[[5-HT1D receptor|5-HT<sub>1D</sub>]] receptor agonist<ref>{{cite journal | vauthors = Syed YY | title = Sumatriptan/Naproxen Sodium: A Review in Migraine | journal = Drugs | volume = 76 | issue = 1 | pages = 111–121 | date = January 2016 | pmid = 26628293 | doi = 10.1007/s40265-015-0521-8 | s2cid = 25060147 }}</ref> can create common side effects such as [[chest pressure]], fatigue, vomiting, [[tingling]], and [[vertigo]]. Serious side effects may include [[serotonin syndrome]], [[heart attack]], [[stroke]], and [[seizure]]s. With excessive use, [[medication overuse headache]]s may occur.<ref name=AHFS2019/> It is unclear if use during [[pregnancy]] or [[breastfeeding]] is safe.<ref name=Preg2019>{{cite web |title=Sumatriptan Use During Pregnancy |url=https://www.drugs.com/pregnancy/sumatriptan.html |website=Drugs.com |access-date=3 March 2019 }}</ref> The mechanism of action is not entirely clear. It is in the [[triptan]] class of medications.<ref name=AHFS2019/>

<!-- Society and culture -->
Sumatriptan was patented in 1982 and approved for medical use in 1991.<ref name=Fis2006>{{cite book | vauthors = Fischer J, Ganellin CR |title=Analogue-based Drug Discovery |date=2006 |publisher=John Wiley & Sons |isbn=9783527607495 |page=531 |url=https://books.google.com/books?id=FjKfqkaKkAAC&pg=PA531 }}</ref> It is on the [[WHO Model List of Essential Medicines|World Health Organization's List of Essential Medicines]].<ref name="WHO22nd">{{cite book | vauthors = ((World Health Organization)) | title = World Health Organization model list of essential medicines: 22nd list (2021) | year = 2021 | hdl = 10665/345533 | author-link = World Health Organization | publisher = World Health Organization | location = Geneva | id = WHO/MHP/HPS/EML/2021.02 | hdl-access=free }}</ref> It is available as a [[generic medication]].<ref name=BNF76/> In 2022, it was the 95th most commonly prescribed medication in the United States, with more than 6{{nbsp}}million prescriptions.<ref>{{cite web | title=The Top 300 of 2022 | url=https://clincalc.com/DrugStats/Top300Drugs.aspx | website=ClinCalc | access-date=30 August 2024 | archive-date=30 August 2024 | archive-url=https://web.archive.org/web/20240830202410/https://clincalc.com/DrugStats/Top300Drugs.aspx | url-status=live }}</ref><ref>{{cite web | title = Sumatriptan Drug Usage Statistics, United States, 2013 - 2022 | website = ClinCalc | url = https://clincalc.com/DrugStats/Drugs/Sumatriptan | access-date = 30 August 2024 }}</ref> It is also available as the combination product [[sumatriptan/naproxen]].

==Medical uses==
Sumatriptan is effective for ending or relieving the intensity of [[migraine]] and [[cluster headache]]s.<ref name=Der2014/> It is most effective when taken early after the start of the pain.<ref name=Der2014>{{cite journal | vauthors = Derry CJ, Derry S, Moore RA | title = Sumatriptan (all routes of administration) for acute migraine attacks in adults - overview of Cochrane reviews | journal = The Cochrane Database of Systematic Reviews | volume = 2014 | issue = 5 | pages = CD009108 | date = May 2014 | pmid = 24865446 | pmc = 6469574 | doi = 10.1002/14651858.CD009108.pub2 }}</ref> Injected sumatriptan is more effective than other formulations.<ref>{{cite journal | vauthors = Dahlöf CG | title = Sumatriptan: pharmacological basis and clinical results | journal = Current Medical Research and Opinion | volume = 17 | pages = s35–s45 | year = 2001 | issue = Suppl 1 | pmid = 12463276 | doi = 10.1185/0300799039117010 | url = http://www.medscape.com/viewarticle/429671_4 | access-date = 16 July 2016 | url-status = live | s2cid = 2355125 | df = dmy-all | archive-url = https://web.archive.org/web/20170217060845/http://www.medscape.com/viewarticle/429671_4 | archive-date = 17 February 2017 | url-access = subscription }}</ref>

Oral sumatriptan can be used also in the treatment of post-dural puncture headache.<ref>{{cite journal| vauthors = Shaat AM, Abdalgaleil MM |date=1 January 2021|title=Is theophylline more effective than sumatriptan in the treatment of post-dural puncture headache? A randomized clinical trial|journal=Egyptian Journal of Anaesthesia|volume=37|issue=1|pages=310–316|doi=10.1080/11101849.2021.1949195|issn=1110-1849|doi-access=free}}</ref>

==Adverse effects==
Overdose of sumatriptan can cause [[sulfhemoglobinemia]], a rare condition in which the blood changes from red to green, due to the integration of [[sulfur]] into the [[hemoglobin]] molecule. If sumatriptan is discontinued, the condition reverses within a few weeks.<ref>{{cite news |date=8 June 2007 |title=Patient bleeds dark green blood |url=http://news.bbc.co.uk/2/hi/health/6733203.stm |url-status=live |archive-url=https://web.archive.org/web/20100805042210/http://news.bbc.co.uk/2/hi/health/6733203.stm |archive-date=5 August 2010 |access-date=6 March 2010 |work=BBC News |df=dmy-all}}</ref>

Serious cardiac events, including some that have been fatal, have occurred following the use of sumatriptan injection or tablets. Events reported have included [[coronary artery vasospasm]], transient myocardial ischemia, [[myocardial infarction]], [[ventricular tachycardia]], and [[ventricular fibrillation]].<ref>{{cite journal | vauthors = Kelly KM | title = Cardiac arrest following use of sumatriptan | journal = Neurology | volume = 45 | issue = 6 | pages = 1211–1213 | date = June 1995 | pmid = 7783891 | doi = 10.1212/wnl.45.6.1211 | s2cid = 35168945 }}</ref> There are reports of [[Takotsubo cardiomyopathy]] and transient [[amnesia]] after sumatriptan use.<ref>{{Cite journal | vauthors = Chohan A |date=2023-03-07 |title=Sumatriptan-Induced Takotsubo Cardiomyopathy  |url=https://linkinghub.elsevier.com/retrieve/pii/S0735109723039426 |journal=Journal of the American College of Cardiology |series=ACC.23 |volume=81 |issue=8, Supplement |pages=3498 |doi=10.1016/S0735-1097(23)03942-6 |issn=0735-1097}}</ref>

The most common side effects<ref>{{cite web |url = https://www.fda.gov/ohrms/dockets/ac/05/briefing/2005-4180b_09_05_Imitrex%20label%20tablet%2012-04%20Sponsor.pdfsumatriptan |title = Tablets |website = fda.gov |access-date = 19 February 2018 }}{{dead link|date=May 2025|bot=medic}}{{cbignore|bot=medic}}</ref> reported by at least 2% of patients in controlled trials of sumatriptan (25-, 50-, and 100-mg tablets) for migraine are atypical sensations ([[paresthesias|paresthesia]] and warm/cold sensations) reported by 4% in the placebo group and 5–6% in the sumatriptan groups, pain and other pressure sensations (including [[chest pain]]) reported by 4% in the placebo group and 6–8% in the sumatriptan groups, neurological events ([[vertigo]]) reported by less than 1% in the placebo group and less than 1% to 2% in the sumatriptan groups. [[Malaise]]/[[fatigue]] occurred in less than 1% of the placebo group and 2–3% of the sumatriptan groups. [[Sleep disorder|Sleep disturbance]] occurred in less than 1% in the placebo group to 2% in the sumatriptan group.

Sumatriptan has a low [[abuse potential]];<ref>{{cite journal | vauthors = Sullivan JT, Preston KL, Testa MP, Busch M, Jasinski DR | title = Psychoactivity and abuse potential of sumatriptan | journal = Clinical Pharmacology and Therapeutics | volume = 52 | issue = 6 | pages = 635–642 | date = December 1992 | pmid = 1333934 | doi = 10.1038/clpt.1992.202 }}</ref> however overuse is associated with [[medication overuse headache]].<ref>{{Cite web |title=TGA eBS - Product and Consumer Medicine Information |url=https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/PICMI?OpenForm&t=pi&q=sumatriptan |access-date=2025-03-03 |website=www.ebs.tga.gov.au}}</ref> Moreover, prolonged sumatriptan use is associated with pronociceptive effects, resulting in [[allodynia]]. This effect's association with medication overuse headache, however, is controversial, due to the fact that animal-model studies are not consistent with typical presentation of this disorder.<ref>{{Cite journal | vauthors = Chiarugi A, Buonvicino D |date=2025-01-01 |title=Critical reflections on medication overuse headache in patients with migraine: An unsolved riddle in nociception |journal=Neurobiology of Pain |volume=17 |pages=100179 |doi=10.1016/j.ynpai.2025.100179 |pmid=40040782 |issn=2452-073X|pmc=11876746 }}</ref>

== Interactions ==
Concurrent use with other [[Triptan|triptans]] or ergot-containing medications (e.g., [[ergotamine]], [[dihydroergotamine]]) within 24 hours can result in additive [[vasoconstriction]].<ref name="DailyMed">{{Cite web |title=DailyMed - SUMATRIPTAN- sumatriptan succinate tablet tablet |url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=2abc46d5-1810-469d-8d31-fafa7312421c |access-date=2024-05-03 |website=dailymed.nlm.nih.gov}}</ref><ref name="Medical_Letter_2023">{{Cite journal |title=Drugs for Migraine | journal = The Medical Letter on Drugs and Therapeutics | date = June 2023 | volume = 65 | issue = 678 | pages = 89–96| publisher = The Medical Letter Inc. | doi = 10.58347/tml.2023.1678a |url=https://secure.medicalletter.org/TML-article-1678a#:~:text=Subcutaneous%20sumatriptan%20is%20the%20most,in%20patients%20with%20vascular%20disease. |access-date=2024-05-03 |language=en}}</ref> Increased systemic exposure to sumatriptan can occur if used within 2 weeks after a [[monoamine oxidase inhibitor]] (MAOI).<ref name="Medical_Letter_2023" /> Cases of [[serotonin syndrome]] have been reported with co-administration of triptans and [[Serotonin reuptake inhibitor|serotonin reuptake inhibitors]].<ref name="DailyMed" />

==Pharmacology==

=== Mechanism of action ===
{| class="wikitable" class="wikitable floatright sortable"
|+<small>Receptor affinities of sumatriptan</small>
!<small>Receptor</small>
!<small>pK<sub>i</sub></small>
!<small>Source</small>
|-
|<small>'''5-HT<sub>1A</sub>'''</small>
|<small>5.99-6.59</small>
|<small><ref name="Boess_1994">{{cite journal | vauthors = Boess FG, Martin IL | title = Molecular biology of 5-HT receptors | journal = Neuropharmacology | volume = 33 | issue = 3–4 | pages = 275–317 | date = March 1994 | pmid = 7984267 | doi = 10.1016/0028-3908(94)90059-0 }}</ref></small>
|-
| rowspan="2" |<small>'''5-HT<sub>1B</sub>'''</small>
|<small>8.7 (human)</small>
|<small><ref name="Boess_1994" /></small>
|-
|<small>6.33-7.35 (rat)</small>
|<small><ref>{{cite journal | vauthors = Hamblin MW, Metcalf MA, McGuffin RW, Karpells S | title = Molecular cloning and functional characterization of a human 5-HT1B serotonin receptor: a homologue of the rat 5-HT1B receptor with 5-HT1D-like pharmacological specificity | journal = Biochemical and Biophysical Research Communications | volume = 184 | issue = 2 | pages = 752–759 | date = April 1992 | pmid = 1315531 | doi = 10.1016/0006-291X(92)90654-4 }}</ref></small>
|-
|<small>'''5-HT<sub>1Dα</sub>'''</small>
|<small>8.73-8.47</small>
|<small><ref name="Boess_1994" /></small>
|-
|<small>'''5-HT<sub>1Dβ</sub>'''</small>
|<small>7.21-8.11</small>
|<small><ref name="Boess_1994" /></small>
|-
|<small>'''5-HT<sub>1E</sub>'''</small>
|<small>5.68</small>
|<small><ref name="Boess_1994" /></small>
|-
|<small>'''5-HT<sub>1F</sub>'''</small>
|<small>7.1-7.64</small>
|<small><ref name="Boess_1994" /></small>
|-
|<small>'''5-HT<sub>2B</sub>'''</small>
|<small><6</small>
|<small><ref name="Boess_1994" /></small>
|-
|<small>'''5-HT<sub>2C</sub>'''</small>
|<small><5</small>
|<small><ref>{{cite journal | vauthors = Bonhaus DW, Weinhardt KK, Taylor M, DeSouza A, McNeeley PM, Szczepanski K, Fontana DJ, Trinh J, Rocha CL, Dawson MW, Flippin LA, Eglen RM | title = RS-102221: a novel high affinity and selective, 5-HT2C receptor antagonist | journal = Neuropharmacology | volume = 36 | issue = 4–5 | pages = 621–629 | date = April 1997 | pmid = 9225287 | doi = 10.1016/S0028-3908(97)00049-X }}</ref></small>
|-
|<small>'''5-HT<sub>4</sub>'''</small>
|<small><5 (guinea pig)</small>
|<small><ref name="Boess_1994" /></small>
|-
|<small>'''5-HT<sub>5A</sub>'''</small>
|<small>4.8-6.8 (mouse)</small>
|<small><ref name="Boess_1994" /></small>
|-
| rowspan="2" |<small>'''5-HT<sub>5B</sub>'''</small>
|<small>5.1 (mouse)</small>
|<small><ref name="Boess_1994" /></small>
|-
|<small>6.09 (rat)</small>
|<small><ref name="Boess_1994" /></small>
|-
|<small>'''5-HT<sub>6</sub>'''</small>
|<small><5.59</small>
|<small><ref>{{cite journal | vauthors = Kohen R, Metcalf MA, Khan N, Druck T, Huebner K, Lachowicz JE, Meltzer HY, Sibley DR, Roth BL, Hamblin MW | title = Cloning, characterization, and chromosomal localization of a human 5-HT6 serotonin receptor | journal = Journal of Neurochemistry | volume = 66 | issue = 1 | pages = 47–56 | date = January 1996 | pmid = 8522988 | doi = 10.1046/j.1471-4159.1996.66010047.x }}</ref><ref>{{cite journal | vauthors = Hirst WD, Abrahamsen B, Blaney FE, Calver AR, Aloj L, Price GW, Medhurst AD | title = Differences in the central nervous system distribution and pharmacology of the mouse 5-hydroxytryptamine-6 receptor compared with rat and human receptors investigated by radioligand binding, site-directed mutagenesis, and molecular modeling | journal = Molecular Pharmacology | volume = 64 | issue = 6 | pages = 1295–1308 | date = December 2003 | pmid = 14645659 | doi = 10.1124/mol.64.6.1295 }}</ref></small>
|-
|<small>'''5-HT<sub>7</sub>'''</small>
|<small>6-7</small>
|<small><ref name="Boess_1994" /></small>
|-
|<small>'''CB1'''</small>
|<small><5</small>
|<small><ref>{{cite journal | vauthors = Plassat JL, Boschert U, Amlaiky N, Hen R | title = The mouse 5HT5 receptor reveals a remarkable heterogeneity within the 5HT1D receptor family | journal = The EMBO Journal | volume = 11 | issue = 13 | pages = 4779–4786 | date = December 1992 | pmid = 1464308 | pmc = 556953 | doi = 10.1002/j.1460-2075.1992.tb05583.x }}</ref></small>
|-
| colspan="3" |<small>The bigger pK<sub>i</sub> value, the stronger receptor affinity</small>
|}
{{Further|Serotonin receptor agonist|Triptan#Mechanism_of_action}}
Sumatriptan is molecularly similar to [[serotonin]] (5-HT), and is a [[5-HT receptor]] (types [[5-HT1D|5-HT<sub>1D</sub>]] and [[5-HT1B|5-HT<sub>1B</sub>]]<ref>
{{cite journal | vauthors = Razzaque Z, Heald MA, Pickard JD, Maskell L, Beer MS, Hill RG, Longmore J | title = Vasoconstriction in human isolated middle meningeal arteries: determining the contribution of 5-HT1B- and 5-HT1F-receptor activation | journal = British Journal of Clinical Pharmacology | volume = 47 | issue = 1 | pages = 75–82 | date = January 1999 | pmid = 10073743 | pmc = 2014192 | doi = 10.1046/j.1365-2125.1999.00851.x }}</ref>) [[agonist]]. Sumatriptan's primary therapeutic effect is related in its inhibition of the release of [[calcitonin gene-related peptide]] (CGRP), likely through its 5-HT<sub>1D/1B</sub> receptor agonist action.<ref>{{cite journal | vauthors = Juhasz G, Zsombok T, Jakab B, Nemeth J, Szolcsanyi J, Bagdy G | title = Sumatriptan causes parallel decrease in plasma calcitonin gene-related peptide (CGRP) concentration and migraine headache during nitroglycerin induced migraine attack | journal = Cephalalgia | volume = 25 | issue = 3 | pages = 179–183 | date = March 2005 | pmid = 15689192 | doi = 10.1111/j.1468-2982.2005.00836.x | s2cid = 13007101 }}</ref> This has been substantiated by the efficacy of more recently developed CGRP targeting drugs and antibodies developed for the preventive treatment of migraine.<ref>{{cite journal | vauthors = Tso AR, Goadsby PJ | title = Anti-CGRP Monoclonal Antibodies: the Next Era of Migraine Prevention? | journal = Current Treatment Options in Neurology | volume = 19 | issue = 8 | pages = 27 | date = August 2017 | pmid = 28653227 | pmc = 5486583 | doi = 10.1007/s11940-017-0463-4 }}</ref> How agonism of the 5-HT<sub>1D/1B</sub> receptors inhibits CGRP release is not fully understood. CGRP is believed to cause sensitization of trigeminal [[Nociception|nociceptive]] neurons, contributing to the pain experienced in migraine.<ref>{{cite journal | vauthors = Giniatullin R, Nistri A, Fabbretti E | title = Molecular mechanisms of sensitization of pain-transducing P2X3 receptors by the migraine mediators CGRP and NGF | journal = Molecular Neurobiology | volume = 37 | issue = 1 | pages = 83–90 | date = February 2008 | pmid = 18459072 | doi = 10.1007/s12035-008-8020-5 | s2cid = 25689799 }}</ref>

Sumatriptan is also shown to decrease the activity of the [[trigeminal nerve]], which presumably accounts for sumatriptan's efficacy in treating cluster headaches. The injectable form of the drug has been shown to abort a cluster headache within 30 minutes in 77% of cases.<ref>{{cite journal | vauthors =  Ekbom K, Waldenlind E, Richard L, Andersson B, Boivie J, Dizdar N, etal | title = Treatment of acute cluster headache with sumatriptan | journal = The New England Journal of Medicine | volume = 325 | issue = 5 | pages = 322–326 | date = August 1991 | pmid = 1647496 | doi = 10.1056/NEJM199108013250505 | collaboration = Sumatriptan Cluster Headache Study Group | doi-access = free }}</ref>

=== Pharmacokinetics ===
Sumatriptan is administered in several forms: tablets, [[subcutaneous injection]], and nasal spray. Oral administration (as [[succinate]] salt) has low [[bioavailability]], partly due to [[presystemic metabolism]]—some of it gets broken down in the stomach and bloodstream before it reaches the target arteries. A rapid-release tablet formulation with the same bioavailability but a high concentration can achieve therapeutic effects on average 10–15 minutes earlier than other oral formulations.<ref>{{Cite web |title=Sumatriptan |url=https://go.drugbank.com/drugs/DB00669 |access-date=2025-03-04 |website=go.drugbank.com |language=en}}</ref> When injected, sumatriptan is faster-acting (usually within 10 minutes), but the effect lasts for a shorter time.{{Citation needed|date=March 2025}}

There is no simple, direct relationship between sumatriptan concentration (pharmacokinetics) per se in the blood and its anti-migraine effect (pharmacodynamics). This paradox has, to some extent, been resolved by comparing the rates of absorption of the various sumatriptan formulations, rather than the absolute amounts of drug that they deliver.<ref>{{cite journal |vauthors=Fox AW |date=February 2004 |title=Onset of effect of 5-HT1B/1D agonists: a model with pharmacokinetic validation |journal=Headache |volume=44 |issue=2 |pages=142–147 |doi=10.1111/j.1526-4610.2004.04030.x |pmid=14756852 |s2cid=25587940}}</ref><ref>{{cite journal |vauthors=Freidank-Mueschenborn E, Fox AW |date=June 2005 |title=Resolution of concentration-response differences in onset of effect between subcutaneous and oral sumatriptan |journal=Headache |volume=45 |issue=6 |pages=632–637 |doi=10.1111/j.1526-4610.2005.05129a.x |pmid=15953294 |s2cid=20755695}}</ref>

==== Metabolism ====
Sumatriptan is metabolised primarily by [[Monoamine oxidase|monoamine oxidase A]] into indol-3-yl-acetaldehyde and then into corresponding carboxylic acid. It is further modified by [[Glucuronosyltransferase|UDP-glucuronosyltransferase]] into a conjugate with [[glucuronic acid]]. Other pathways are mediated by [[Cytochrome P450 (individual enzymes)|cytochrome P450 isoenzymes]], which give an [[Amine oxide|''N''-oxide]] derivative, and ''N''-desmethyl and ''N,N''-didesmethyl forms (the latter can be converted into the aldehyde by monoamine oxidase A). ''N''-desmethyl derivative can also undergo a reaction with [[Cysteine|<small>D</small>-cysteine]].<ref name="Pöstges_2023">{{cite journal | vauthors = Pöstges T, Lehr M | title = Metabolism of sumatriptan revisited | journal = Pharmacology Research & Perspectives | volume = 11 | issue = 1 | pages = e01051 | date = February 2023 | pmid = 36655303 | pmc = 9849828 | doi = 10.1002/prp2.1051 }}</ref>

These metabolites are excreted in the urine and bile. Only about 3% of the active drug may be recovered unchanged.<ref name="AHFS2019" />
[[File:Sumatriptan metabolism pathway.png|center|thumb|881x881px|Sumatriptan metabolic pathways (MAO-A – monoamine oxidase A, CYP - cytochrome P450 isoenzymes)<ref name="Pöstges_2023" />]]

==History==
[[File:Sumatriptan vails 100 5509.jpg|thumb|Sumatriptan vials]]

In 1991, Glaxo received approval for sumatriptan, which was the first available [[triptan]].{{Citation needed|date=March 2025}}

In July 2009, the US [[Food and Drug Administration]] (FDA) approved a single-use [[jet injector]] formulation of sumatriptan. The device delivers a subcutaneous injection of sumatriptan, without the use of a needle. [[Autoinjector]]s with needles have been previously available in Europe and North America.<ref name=Brandes>{{cite journal | vauthors = Brandes JL, Cady RK, Freitag FG, Smith TR, Chandler P, Fox AW, Linn L, Farr SJ | title = Needle-free subcutaneous sumatriptan (Sumavel DosePro): bioequivalence and ease of use | journal = Headache | volume = 49 | issue = 10 | pages = 1435–1444 | year = 2009 | pmid = 19849720 | doi = 10.1111/j.1526-4610.2009.01530.x | s2cid = 25696109 }}</ref>

Phase III studies with an [[iontophoretic]] [[transdermal patch]] (Zelrix/Zecuity) started in July 2008.<ref>{{ClinicalTrialsGov|NCT00724815|The Efficacy and Tolerability of NP101 Patch in the Treatment of Acute Migraine (NP101-007)}}</ref> This patch uses low [[voltage]] controlled by a pre-programmed [[Integrated circuit|microchip]] to deliver a single dose of sumatriptan through the skin within 30 minutes.<ref>{{cite web |url = http://www.nupathe.com/description.php?secid=3&subsecid=7#_ELECTRONIC_DRUG |title = SmartRelief -electronically assisted drug delivery (iontophoresis) |website = nupathe.com |access-date = 19 February 2018 |url-status = live |archive-url = https://web.archive.org/web/20160107062814/http://www.nupathe.com/description.php?secid=3&subsecid=7#_ELECTRONIC_DRUG |archive-date = 7 January 2016 |df = dmy-all }}</ref><ref>{{cite journal | vauthors = Pierce M, Marbury T, O'Neill C, Siegel S, Du W, Sebree T | title = Zelrix: a novel transdermal formulation of sumatriptan | journal = Headache | volume = 49 | issue = 6 | pages = 817–825 | date = June 2009 | pmid = 19438727 | doi = 10.1111/j.1526-4610.2009.01437.x | s2cid = 205683188 | doi-access = free }}</ref> Zecuity was approved by the FDA in January 2013.<ref>{{cite web |url = http://ir.nupathe.com/press-releases/nupathe-s-zecuity-approved-by-the-fda-for-the-acut-nasdaq-path-975802NuPathe's |title = Zecuity Approved by the FDA for the Acute Treatment of Migraine |website = nupathe.com |access-date = 19 February 2018 |url-status = live |archive-url = https://web.archive.org/web/20160107062814/http://ir.nupathe.com/press-releases/nupathe-s-zecuity-approved-by-the-fda-for-the-acut-nasdaq-path-975802NuPathe's |archive-date = 7 January 2016 |df = dmy-all }}</ref> Sales of Zecuity have been stopped following reports of skin burns and irritation.<ref>{{cite web|url=http://www.fiercepharma.com/pharma/teva-pulls-migraine-patch-zecuity-reports-burning-scarring|title=Teva pulls migraine patch Zecuity on reports of burning, scarring |website=FiercePharma |date=13 June 2016 |access-date=10 April 2017|url-status=live|archive-url=https://web.archive.org/web/20170321022606/http://www.fiercepharma.com/pharma/teva-pulls-migraine-patch-zecuity-reports-burning-scarring|archive-date=21 March 2017}}</ref>

== Society and culture ==
=== Legal status ===
In the United States, it is available only by medical prescription. It is available over the counter in many states in Australia. The product requires labelling by a pharmacist and is only available in packs of two without a medical prescription.<ref>{{cite web |title = Poisons Standard June 2017 |url = https://www.legislation.gov.au/Details/F2017L00605/Html/Text#_Toc471222305 |access-date = 22 July 2017 |date = 18 May 2017 |url-status = live |archive-url = https://web.archive.org/web/20170731114704/https://www.legislation.gov.au/Details/F2017L00605/Html/Text#_Toc471222305 |archive-date = 31 July 2017 |df = dmy-all }}</ref> However, it can be bought over the counter in the UK<ref>{{cite web |title = Press release: First Over The Counter (OTC) migraine pill made available |url = http://www.mhra.gov.uk/NewsCentre/Pressreleases/CON2023768 |publisher = Medicines and Healthcare Products Regulatory Agency |access-date = 28 January 2015 |archive-url = http://webarchive.nationalarchives.gov.uk/20141205150130/http://www.mhra.gov.uk/NewsCentre/Pressreleases/CON2023768 |archive-date = 5 December 2014 }}</ref> and Sweden.<ref>{{cite web |author1 = European Medicines Agency |author-link1 = European Medicines Agency |title = Assessment Report: Sumatriptan Galpharm 50 mg Tablets |url = http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Public_assessment_report/human/002140/WC500122862.pdf |publisher = European Medicines Agency |access-date = 28 January 2015 |page = 20 |date = 23 November 2011 |url-status = live |archive-url = https://web.archive.org/web/20160107062816/http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Public_assessment_report/human/002140/WC500122862.pdf |archive-date = 7 January 2016 |df = dmy-all }}</ref>

In Russia, versions of sumatriptan which are not registered in the State Register of Medicines may be regarded as narcotic drugs (derivatives of [[N,N-Dimethyltryptamine|dimethyltryptamine]]).<ref name="Order681">{{cite web|url=http://base.garant.ru/12112176/|title=Постановление Правительства РФ от 30 июня 1998 г. N 681 "Об утверждении перечня наркотических средств, психотропных веществ и их прекурсоров, подлежащих контролю в Российской Федерации" (с изменениями и дополнениями)|quote=ДМТ (диметилтриптамин) и его производные, за исключением производных, включенных в качестве самостоятельных позиций в перечень|publisher=[[Гарант (справочно-правовая система)|Гарант]]|access-date=28 April 2019|language=ru}}</ref>

===Generics===
Glaxo patents for sumatriptan expired in February 2009. At that time, Imitrex sold for about $25 a pill.<ref>{{cite web |title=GlaxoSmithKline sets out to dupe migraine sufferers with Treximet smoke and mirrors |date=24 April 2008 |publisher=Community Catalyst |url=https://www.communitycatalyst.org/blog/glaxosmithkline-sets-out-to-dupe-migraine-sufferers-with-treximet-smoke-and-mirrors-pal |access-date=22 March 2019}}</ref> [[Par Pharmaceutical]] then introduced generic versions of sumatriptan injection (sumatriptan succinate injection) 4- and 6-mg starter kits and 4- and 6-mg filled syringe cartridges, and 6-mg vials soon after.<ref>{{cite news |title = Par Pharmaceutical begins shipment of sumatriptan injection |url = http://www.parpharm.com/media/NR_20081106.jsp |archive-url = https://web.archive.org/web/20081210132734/http://www.parpharm.com/media/NR_20081106.jsp |url-status = dead |archive-date = 10 December 2008 |work = Par Pharmaceutical |date = 6 November 2008 |access-date = 25 November 2008 |df = dmy-all }}</ref>

[[Mylan|Mylan Laboratories Inc.]], [[Ranbaxy Laboratories]], Sandoz (a subsidiary of [[Novartis]]), [[Dr. Reddy's Laboratories]], and other companies have been producing generic versions of sumatriptan tablets in 25-, 50-, and 100-mg doses. Generic forms of the drug are available in U.S. and European markets after Glaxo's patent protections expired in the respective countries. A nasal spray form of sumatriptan known as AVP-825 has been developed by Avanir and is generically available in some countries.<ref>{{cite news | vauthors = LaMattina J |title = If You 'Want To Make A Good Drug Great' Cost Must Be Factored In |url = https://www.forbes.com/sites/johnlamattina/2015/03/03/if-you-want-to-make-a-good-drug-great-cost-must-be-factored-in/ |access-date = 13 February 2017 |work = Forbes |date = 2 March 2015 |url-status = live |archive-url = https://web.archive.org/web/20170214105140/http://www.forbes.com/sites/johnlamattina/2015/03/03/if-you-want-to-make-a-good-drug-great-cost-must-be-factored-in/ |archive-date = 14 February 2017 |df = dmy-all }}</ref>

=== Controversy ===
According to the [[American Headache Society]], "Patients frequently state that they have difficulty accessing triptans prescribed to them."<ref name="headache">{{Citation | vauthors=((Minen, M. T.)), ((Lindberg, K.)), ((Langford, A.)), ((Loder, E.)) | year=2017 | title=Variation in Prescription Drug Coverage for Triptans: Analysis of Insurance Formularies | journal=Headache: The Journal of Head and Face Pain | volume=57 | issue=8 | pages=1243–1251 | publisher=Wiley | doi=10.1111/head.13134 | pmid=28691382 | s2cid=42239120 | url=http://dx.doi.org/10.1111/head.13134| url-access=subscription }}</ref> In the U.S. triptans cost from $12 to $120 each, and more than 80% of U.S. health insurance plans place a limit on the amount of pills available to a patient per month, which has been called "arbitrary and unfair."<ref>{{citation |title=Practice Matters Wide Variation in Triptan Coverage Across Commercial and Government Health Plans | vauthors = Bender E |date=7 September 2017 |journal=[[Neurology Today]] |volume=17 |issue=17 |page=7 |publisher=[[American Academy of Neurology]] |doi=10.1097/01.NT.0000524839.20893.03 |s2cid=80167113 |url=https://journals.lww.com/neurotodayonline/fulltext/2017/09070/Practice_Matters__Wide_Variation_in_Triptan.4.aspx |access-date=26 June 2022|url-access=subscription }}</ref>

== References ==
{{Reflist}}

{{Serotonergics}}
{{Triptans}}
{{Tryptamines}}
{{GlaxoSmithKline}}
{{Portal bar | Medicine}}

[[Category:5-HT1B agonists]]
[[Category:5-HT1D agonists]]
[[Category:5-HT1F agonists]]
[[Category:N,N-Dialkyltryptamines]]
[[Category:Dimethylamino compounds]]
[[Category:Drugs developed by Pfizer]]
[[Category:Drugs developed by GSK plc]]
[[Category:Sulfonamides]]
[[Category:Triptans]]
[[Category:World Health Organization essential medicines]]
[[Category:Wikipedia medicine articles ready to translate]]