Triptans are a family of tryptamine-based drugs used as abortive medication in the treatment of migraines and cluster headaches.

The drugs of this class act as agonists for serotonin 5-HT1B and 5-HT1D receptors at blood vessels and nerve endings in the brain.

Triptans have largely replaced ergotamines, an older class of medications used to relieve migraine and cluster headaches.

[19][20] 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.

[1] In spite of expert opinion and evidence to the contrary, the FDA and some other drug governance bodies have stated that monoamine oxidase inhibitors are contraindicated for sumatriptan, zolmitriptan and rizatriptan,[21][22] and combination with ergot alkaloids such as ergotamine for all substances.

[24] There is a theoretical risk of coronary spasm in patients with established heart disease, and cardiac events after taking triptans may rarely occur.

[25] Combination of triptans with other serotonergic drugs such as ergot alkaloids, monoamine oxidase inhibitors, selective serotonin reuptake inhibitors (SSRIs), serotonin–norepinephrine reuptake inhibitors (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),[1][10] 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.

[10] 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 depression with a triptan for migraine did not demonstrate an increased risk of the serotonin syndrome.

[33] Pharmacokinetic interactions (for example, mediated by CYP liver enzymes or transporter proteins) are different for the individual substances; for most triptans, they are mild to absent.

[10] Their action is attributed to their agonist[34] effects on serotonin 5-HT1B and 5-HT1D receptors in blood vessels (causing their constriction) and nerve endings in the brain, and subsequent inhibition of pro-inflammatory neuropeptide release, including CGRP and substance P. Triptans are selective agents for 5-HT1B and 5-HT1D[34] and have low or even no affinity for other types of 5-HT receptors.

[35] Most mammalian species, including humans, have 5-HT1D binding sites widely distributed throughout the central nervous system.

Also they are thought to promote neurogenic inflammatory response important for sensitization of sensory afferents, and also transmission and generation of head pain centrally.

5-HT1D has been found responsible for inhibition of neurogenic inflammation upon administration with sumatriptan and other related compounds that act on prejunctional 5-HT1D receptors.

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.

[22][38][39][40] Zolmitriptan is different from the other triptans because it is converted to an active N-desmethyl metabolite which has higher affinity for the 5-HT1D and 5-HT1B receptors; both substances have a biological half-life of 2 to 3 hours.

Humphrey among others at Glaxo started researching the 5-HT receptor to discover a more direct 5-HT agonist with fewer side effects.

[citation needed] Sumavel Dosepro is a needle-free delivery of injectable sumatriptan that was approved in the US by the FDA in July 2009.