Common Mechanism of Action for Abortive Migraine Therapies
The most common mechanism of action for abortive migraine therapies is serotonin (5-HT1B/1D) receptor agonism, which causes cranial vessel constriction and inhibits pro-inflammatory neuropeptide release in the trigeminal system. 1
Primary Mechanism: Serotonin Receptor Agonism
The triptan class of medications—which includes sumatriptan, rizatriptan, zolmitriptan, naratriptan, eletriptan, almotriptan, and frovatriptan—all work through selective 5-HT1B/1D receptor agonism 2, 1. This mechanism produces therapeutic effects through two key pathways:
- Cranial vessel constriction via 5-HT1B receptors on intracranial blood vessels 1
- Inhibition of pro-inflammatory neuropeptide release via 5-HT1D receptors on sensory nerves of the trigeminal system 1
This represents a receptor-targeted, migraine-specific mechanism that distinguishes triptans from non-specific analgesics 3. The mechanism was first validated with sumatriptan and is now recognized as the standard pharmacological approach for moderate to severe migraine attacks 2, 4.
Alternative Mechanisms in Abortive Therapy
While 5-HT1B/1D agonism is the most common migraine-specific mechanism, other abortive therapies work through different pathways:
Non-Selective Serotonin Agonism
- Ergotamine and dihydroergotamine (DHE) are non-selective 5-HT receptor agonists that also produce cranial vasoconstriction 2
- These agents have broader serotonin receptor activity compared to triptans, which explains their higher side effect profile 2
Prostaglandin Inhibition
- NSAIDs (ibuprofen, naproxen, aspirin) work through prostaglandin synthesis inhibition and are recommended as first-line therapy for mild to moderate attacks 2, 4
- This mechanism is non-specific and not migraine-selective, but clinically effective 2
Dopamine Antagonism
- Metoclopramide and prochlorperazine provide headache relief through dopamine receptor antagonism, in addition to treating nausea 2, 5
- These agents offer synergistic analgesia when combined with other abortive medications 4
Clinical Implications of Mechanism
The 5-HT1B/1D receptor agonist mechanism has important clinical consequences:
- Contraindications in vascular disease: Because triptans cause vasoconstriction, they are contraindicated in patients with ischemic vascular conditions, vasospastic coronary disease, uncontrolled hypertension, or significant cardiovascular disease 2
- Route-dependent efficacy: Subcutaneous sumatriptan achieves the highest efficacy (59% pain-free at 2 hours) due to rapid receptor engagement, compared to oral routes 6
- Timing matters: Early administration when pain is mild produces better outcomes than waiting until pain is moderate or severe, likely due to preventing central sensitization 6
Comparative Efficacy by Mechanism
Among the 5-HT1B/1D agonists, eletriptan demonstrates the highest probability (68%) of producing pain-free response at 2 hours, followed by rizatriptan and zolmitriptan 7. This suggests that subtle differences in receptor binding profiles and pharmacokinetics within the same mechanistic class can produce clinically meaningful differences in efficacy 7.