Discovery and development of triptans
Triptans are a group of medicines used to stop migraine and cluster headache attacks. They are based on the chemical family tryptamine and work by selectively activating 5-HT1B/1D receptors. Migraine is a common and often disabling condition, and triptans are typically preferred over older drugs like ergotamines because they target the right receptors, have a solid safety record, and come with clear prescribing guidelines.
The search for a new anti-migraine drug began at Glaxo in 1972. Early research showed that drugs causing cranial blood vessel constriction could help migraines, and that serotonin levels change during a migraine. Scientists wanted to develop a drug that could more precisely target serotonin receptors to reduce side effects. They studied different 5-HT receptor subtypes and created several compounds before hitting the breakthrough with sumatriptan, the first true triptan. Sumatriptan could constrict cranial blood vessels and be taken by mouth, and it was first launched in the Netherlands in 1991 and reached the United States in 1993.
How triptans work: they are selective activators of the 5-HT1B/1D receptors. This leads to relief by constricting inflamed blood vessels in the head and by dampening signals in the trigeminal nerve pathways that drive migraine, without harming overall brain blood flow. The exact details of receptor binding are complex, but the important idea is that triptans target the receptors most involved in migraine.
Structure and design: all triptans share the indole structure related to serotonin, but they differ in the side chains attached to the ring. These differences affect how well they are absorbed, how quickly they work, and how long they last. Some examples of later triptans include zolmitriptan, naratriptan, rizatriptan, almotriptan, eletriptan, and frovatriptan. Each has its own strengths, such as faster onset or longer effect, which helps doctors tailor treatment to the patient.
Forms and delivery: triptans are available as tablets, orally disintegrating tablets, nasal sprays, injections, and even rectal forms. The method of delivery influences how quickly relief begins. For a fast-developing attack, nasal spray or injection can be quicker than pills, though many people use tablets or dissolving tablets for convenience.
Choosing a triptan: doctors consider the patient’s symptoms, how quickly they need relief, and how they tolerate different forms. Some forms may work faster but have different side effects, while others may be easier to use regularly.
Combination therapy: in 2008 the FDA approved a fixed-dose combination of sumatriptan 85 mg with naproxen 500 mg (an NSAID). Using two medicines with different ways of attacking migraine can improve relief for some people.
What’s next: most triptans were developed in the 1990s, and while researchers continue to explore new options, there hasn’t been a clearly better new triptan. Future anti-migraine drugs are likely to target different mechanisms beyond the ones used by triptans.
This page was last edited on 3 February 2026, at 01:48 (CET).