Category:Triptans

A triptan is a member of the medicine class of serotonin 5-HT1B and 5-HT1D receptor agonists used to abort an acute migraine attack. The class is composed of seven medicines licensed in the United States and elsewhere (sumatriptan, rizatriptan, zolmitriptan, almotriptan, eletriptan, naratriptan, and frovatriptan); the eighth, donitriptan, did not reach the market. The triptans are conventionally used as a second-line acute medicine after simple analgesics or non-steroidal anti-inflammatories have proved inadequate, and remain the most effective abortive class for the majority of migraine sufferers despite the more recent introduction of the gepant and ditan classes.

The development of the triptans is the founding event of the modern abortive-migraine pharmacopoeia. Working at Glaxo in the 1980s, Patrick Humphrey hypothesised that the cranial-vessel dilation produced by ergotamine (the historical migraine abortive) was mediated by a specific serotonin receptor subtype, and that a selective agonist at that receptor would provide ergotamine-like efficacy without ergotamine's substantial vasoconstrictor adverse-effect profile.^[1] Sumatriptan (Imitrex, Glaxo 1991 as subcutaneous, 1992 as oral) was the first medicine of the class; the demonstration that subcutaneous sumatriptan aborted a migraine attack in 60 to 70 percent of patients within an hour, compared to the 30 percent placebo response, transformed acute migraine management.

The mechanism of triptan action involves three components, each at a different anatomical site. The first is constriction of the dilated cranial vessels through 5-HT1B receptor agonism on vascular smooth muscle, reversing one of the proximal events of the migraine attack. The second is inhibition of the neurogenic inflammation around cranial vessels through 5-HT1D receptor activation on the perivascular trigeminal nerve terminals, blocking the release of CGRP, substance P, and other neuropeptides that drive the inflammatory cascade. The third is direct inhibition of nociceptive transmission in the trigeminal-cervical complex of the brainstem through 5-HT1D receptor activation on central neurons; this central component is more pronounced in the more lipid-soluble (more blood-brain-barrier-permeable) triptans (eletriptan, zolmitriptan) than in the less lipid-soluble (sumatriptan, naratriptan).

The class members differ in pharmacokinetics. The most rapid-onset triptans (subcutaneous sumatriptan, rizatriptan oral disintegrating tablet, zolmitriptan nasal spray) reach therapeutic effect within 30 to 60 minutes. Sumatriptan oral, the standard formulation, has approximately 14 percent oral bioavailability (limited by first-pass metabolism by monoamine oxidase A; the related contraindication to concurrent MAOIs is among the most clinically important interactions in the category). The longer-half-life triptans (naratriptan, frovatriptan) provide more sustained effect with lower recurrence rates over 24 hours, at the cost of a slower onset. The newer formulations (the sumatriptan-naproxen fixed combination Treximet; the sumatriptan iontophoretic transdermal patch Zecuity, withdrawn 2016 for application-site burns; the sumatriptan nasal-powder Onzetra Xsail; the zolmitriptan oral disintegrating tablet) extend the practical pharmacy of the class.

The contraindications of the triptans reflect their vasoconstrictor mechanism. The class is contraindicated in established ischaemic heart disease (Prinzmetal angina, prior myocardial infarction with residual ischaemia, significant coronary artery disease in patients over the typical age for first migraine onset), in uncontrolled hypertension, in basilar or hemiplegic migraine (where the migraine-associated stroke risk is presumed elevated), in pregnancy (the class is FDA pregnancy category C; sumatriptan has the most data with no clear teratogenic signal), and in concurrent use of an MAOI within 14 days. The interaction with the SSRIs and SNRIs (the theoretical risk of serotonin syndrome with combined 5-HT1 agonist and reuptake inhibitor) has been the subject of a 2006 FDA advisory and substantial subsequent literature; the practical clinical conclusion is that the interaction is real but very rare, and is acceptable in most patients with the standard caution. The most common adverse effects are the so-called "triptan sensations" of chest tightness, throat tightness, paraesthesia, and a transient sense of heaviness, none of which represents ischaemia in the vast majority of patients but each of which is unpleasant enough to cause discontinuation in some.

The introduction of the gepant and ditan classes in 2018 and 2019 (rimegepant, ubrogepant, atogepant, zavegepant for the gepants; lasmiditan for the ditans) extended abortive-migraine pharmacology beyond the triptans for the first time. The gepants are CGRP-receptor antagonists with no vasoconstrictor effect and so are usable in patients with cardiovascular contraindications to triptans. Lasmiditan, a selective 5-HT1F receptor agonist (the 5-HT1F subtype is not present on vascular smooth muscle and so the medicine produces no vasoconstriction), is similarly usable in cardiovascular-contraindicated populations but has substantial CNS sedation that produces a driving restriction. The triptans remain first-line for most patients without contraindication on the basis of greater efficacy, lower cost, and longer clinical experience; the newer abortive medicines are second-line for triptan failures and first-line in patients with cardiovascular concern.

By onset and duration:

• Rapid-onset, short-duration (preferred for rapid-escalation migraine):
  • Sumatriptan (Imitrex; subcutaneous, oral, nasal spray, nasal powder, transdermal historical)
  • Rizatriptan (Maxalt; oral tablet, oral disintegrating tablet)
  • Zolmitriptan (Zomig; oral tablet, oral disintegrating tablet, nasal spray)
  • Eletriptan (Relpax; oral; the most lipid-soluble triptan, with substantial central action)
  • Almotriptan (Axert; oral; somewhat better tolerated profile)
• Slower-onset, longer-duration (preferred for slowly developing migraine and for menstrual migraine prophylaxis):
  • Naratriptan (Amerge; longer half-life ~6 hours; lower headache recurrence)
  • Frovatriptan (Frova; longest half-life ~26 hours; used as short-term menstrual migraine prophylaxis 2-6 days before expected onset)
• Fixed combinations:
  • Sumatriptan-naproxen (Treximet); the combination targets the prostaglandin component of migraine alongside the serotonergic component

The boundary of this category is "medicine in the sumatriptan family of selective 5-HT1B/1D receptor agonists used as acute abortive treatment of migraine." The closely related but mechanistically distinct ergot derivatives (ergotamine, dihydroergotamine) are not triptans; their action involves multiple serotonin and adrenergic receptor subtypes and they have a different (and broader) vasoconstrictor profile. The gepants and ditans (rimegepant, ubrogepant, atogepant, zavegepant, lasmiditan) act on the same migraine syndrome but at different molecular targets and are listed under antimigraine agents and at their individual medicine pages. The medicines for migraine prophylaxis (the beta-blockers, tricyclics, topiramate, divalproex, the CGRP monoclonal antibodies) are listed under migraine prophylaxis separately, although several of the gepants now have both abortive and preventive indications and so are listed in both categories.

This category page is an encyclopedia article about its subject. The actual index of medicines belonging to the category is generated automatically by the wiki engine, from category-membership declarations on the individual medicine pages, and appears at the foot of the page below the references.