Mechanism of Action of Triptans
Triptans act as selective 5-HT1B/1D receptor agonists that exert their therapeutic effects by binding to serotonin receptors on intracranial blood vessels and sensory nerves of the trigeminal system, resulting in cranial vessel constriction and inhibition of pro-inflammatory neuropeptide release. 1, 2
Primary Mechanism of Action
- Triptans selectively bind with high affinity to 5-HT1B and 5-HT1D receptors, with some also binding to 5-HT1F receptors 1
- This binding leads to two primary effects:
Neuronal Effects
- Triptans block synaptic transmission between peripheral trigeminovascular neurons and central trigeminovascular neurons in the dorsal horn 3
- They can prevent the induction of central sensitization in trigeminovascular neurons, which plays an important role in migraine pathophysiology 3
- Triptans have both peripheral and central trigeminal inhibitory effects, as well as actions in the thalamus and central modulatory sites 4
Pharmacological Differences Between Triptans
- While all triptans share the same primary mechanism of action, there are minor pharmacodynamic differences between them 5
- Pharmacokinetic variations exist in:
- Bioavailability (sumatriptan has low oral bioavailability at 14%, newer triptans have improved bioavailability) 5
- Half-life (ranging from approximately 2 hours for sumatriptan to 26-30 hours for frovatriptan) 5
- Time to maximum concentration (rizatriptan has a faster onset than sumatriptan and zolmitriptan) 5
Clinical Implications of Mechanism
- Triptans are most effective when taken early in a migraine attack while pain is still mild 6
- Their selective action on 5-HT1B/1D receptors makes them safer than older non-selective serotonin agonists like ergotamine 7
- Due to their vasoconstrictive properties, triptans are contraindicated in patients with:
- Ischemic vascular conditions
- Vasospastic coronary disease
- Uncontrolled hypertension
- Other significant cardiovascular disease 6
Common Pitfalls and Caveats
- Triptans should not be used during the aura phase of a migraine attack, only during the headache phase 6
- If one triptan is ineffective, another triptan may still provide relief due to slight pharmacological differences 6
- Recurrence of headache within 24 hours after initial successful response occurs in 30-40% of patients 5
- Triptans should not be combined with ergotamine derivatives due to the risk of additive vasoconstrictive effects 6
- There is a theoretical risk of serotonin syndrome when triptans are combined with SSRIs or SNRIs, though this risk is considered low 6
Understanding the mechanism of action of triptans helps explain both their efficacy in treating migraine attacks and the contraindications that must be observed to ensure patient safety.