A patient on sumatriptan for acute migraine develops a new-onset neurological deficit. The prescriber stops sumatriptan and prescribes lasmiditan instead. What is lasmiditan's mechanism that distinguishes it from triptans?

• A CGRP receptor antagonist preventing neurogenic inflammation without vasoconstriction
• B Non-selective serotonin agonist with additional CGRP synthesis inhibition
• C 5-HT1D receptor agonist without cardiac effects due to selective neuronal targeting
• D Selective 5-HT1F receptor agonist with no intrinsic vasoconstrictor activity, targeting trigeminovascular neurons without vascular 5-HT1B receptor activation ✓

Explanation

Triptans (sumatriptan, rizatriptan) are 5-HT1B/1D agonists; the 5-HT1B component causes vasoconstriction of meningeal and coronary arteries, contraindicated in coronary artery disease and cerebrovascular disease. Lasmiditan is a selective 5-HT1F receptor agonist (the 'ditan' class). 5-HT1F receptors are expressed predominantly on trigeminal neurons and not on vascular smooth muscle, so lasmiditan inhibits trigeminovascular activation and neurogenic inflammation without coronary or cerebrovascular vasoconstriction, making it suitable for patients with cardiovascular risk where triptans are contraindicated. CGRP receptor antagonists (gepants) are a separate drug class.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

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