Pharmacology of Triptans

Triptans are medicines used in the treatment of migraine and cluster headaches. They are not used to prevent either of these conditions, nor are they considered a cure. However, they do provide significant symptomatic treatment.

Triptans have been around since the 1990s.

Sumatriptan, the first FDA approved triptan, was made available to the public in 1993. It was long believed that activity at serotonin receptors led to reduced incidence of migraine attacks, but it was not precisely known why. Triptans filled the gap and became an instant success.

Examples of triptans include:

  • Sumatriptan
  • Eletriptan
  • Zolmitriptan
  • Almotriptan
  • Rizatriptan

Though triptans are used to treat cluster headaches and migraines, they are not used to treat other types of headache. For example – they are not used to treat tension headaches.

Mechanism of action

As we alluded to earlier, researchers long knew that a connection existed between migraine and its relief through serotonergic receptors. This research commenced in the 1940s, but it was only in the 1990s that triptans became widely used.

Specifically, triptans work as agonists at 5-HT1B and 5-HT1D receptors. They have activity at other receptor sites, but it’s through their activity at these two receptor sites that accounts for their therapeutic impact.

Agonism at 5-HT1B / 5-HT1D receptors causes vasoconstriction of blood vessels surrounding the brain.

However, triptans also have two other modes of effect:

  • Inhibition of neuropeptide release from nerve terminals. Implicated neuropeptides include Substance P and CGRP, or calcitonin gene-related peptide.
  • Inhibition of nociceptive neurotransmission. This refers to “pain transmission”, which is inhibited at sites such as the brainstem.

These are the three primary ways in which triptans exert their therapeutic impact.

Side effects

Side effects with triptans include:

  • Paresthesias
  • Nausea
  • Chest pain
  • Sweating
  • Muscle pain
  • Weakness
  • Dry mouth

Though triptans are linked to these effects, it’s worth emphasizing that triptans are very well-tolerated drugs.

More rarely, triptans are linked to cardiovascular events, not least because triptans are linked to the risk of high blood pressure.

Sumatriptan overdose is linked to sulfhemoglobinemia – an effect which causes blood to change from red to green. However, once sumatriptan is discontinued from use, the change reverses within a matter of weeks. The condition arises due to the presence of a sulfur group within the hemoglobin molecule.

Clinical considerations

When we think about the clinical pharmacology of triptans, we need to talk about the following factors:

  • That triptans are classified as pregnancy category C in the United States, meaning “risk is not ruled out”. Triptans should be avoided.
  • That triptans are often believed to increase the risk of serotonin syndrome, particularly when taken with SSRIs, SNRIs, MAO inhibitors and St. John’s wort. However, recent research casts doubt on the link / established risk.
  • That due to their hypertensive effects, triptans are avoided in patients with established cardiovascular disease. Despite the risk, the occurrence of serious cardiovascular effects – such as coronary spasm – is regarded as rare.
  • That later triptans have longer half-lives and greater oral bioavailability compared to older agents, such as the founding triptan, sumatriptan.

Triptans remain, then, an important class of medicines in the treatment of migraine and cluster headaches at a time when there is no cure for either condition.

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