Pharmacology · Serotonin Pharmacology

Serotonin in Migraine — Triptans

Triptan mechanism, contraindications, ergot alkaloids, and migraine prophylaxis

Triptans are selective 5-HT1B/1D agonists that abort migraine through two parallel mechanisms: 5-HT1B agonism constricts dilated meningeal vessels, and 5-HT1D agonism on trigeminal terminals inhibits release of CGRP and substance P, blocking neurogenic inflammation at the source.
Sumatriptan is the prototype — subcutaneous injection provides the fastest onset (10–15 minutes); nasal and oral formulations offer alternatives for patients who cannot tolerate injections; take at onset of the headache phase, not during aura, for optimal effect.
Triptans are contraindicated in any vasospastic condition (CAD, uncontrolled hypertension, history of stroke or TIA, hemiplegic or basilar migraine) because 5-HT1B receptors on coronary and cerebral vessels can cause clinically significant vasoconstriction.
Ergotamine and dihydroergotamine act via non-selective serotonin, dopamine, and adrenergic agonism — DHE is given intravenously for refractory migraine; the absolute 24-hour rule prohibits combining triptans and ergots due to additive vasospasm risk.
First-line migraine prophylaxis targets prevention in patients with ≥4 headache days per month: beta-blockers (propranolol, metoprolol), amitriptyline, valproate, and topiramate — with newer anti-CGRP monoclonal antibodies for refractory cases.

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