Triptans Target Serotonin 5-HT1B and 5-HT1D Receptors
Triptans are serotonin (5-HT1B/1D) receptor agonists that work by selectively activating these two specific serotonin receptor subtypes. 1, 2, 3
Primary Receptor Targets
Triptans bind to and activate 5-HT1B receptors, which are located on cranial blood vessels and mediate vasoconstriction of dilated meningeal vessels during migraine attacks 2, 3, 4
Triptans also activate 5-HT1D receptors, which are found on trigeminal nerve terminals and inhibit the release of pro-inflammatory neuropeptides that contribute to migraine pain 2, 3, 4
The dual 5-HT1B/1D receptor agonism explains both the peripheral vascular effects (vasoconstriction) and the neuronal effects (inhibition of trigeminovascular activation) that contribute to triptan efficacy 5, 6
Additional Receptor Activity
Some triptans, particularly sumatriptan and zolmitriptan, can also affect central serotonergic neurotransmission by activating 5-HT1 autoreceptors in the brain, which inhibit serotonin release 7
Newer research has explored 5-HT1F receptor agonists (ditans like lasmiditan) as an alternative mechanism that provides antimigraine effects without the vasoconstrictive properties of 5-HT1B activation 1, 5
Clinical Implications of Receptor Selectivity
The 5-HT1B receptor activation causes vasoconstriction, which is why triptans are contraindicated in patients with ischemic vascular conditions, coronary artery disease, uncontrolled hypertension, and peripheral vascular disease 8, 2
The receptor specificity of triptans represents an improvement over older ergot alkaloids, which bind to multiple receptor types including α-adrenoceptors and dopamine receptors, resulting in more side effects 5
All seven available triptans (sumatriptan, zolmitriptan, rizatriptan, naratriptan, almotriptan, eletriptan, and frovatriptan) share this same 5-HT1B/1D receptor mechanism of action, though they differ in pharmacokinetic properties 1, 4