5–HT_1F receptor agonist (ditan)

Abstract

Treatment of migraine consists of acute and prophylactic therapy. Acute therapy mainly consists of analgesics such as NSAIDs and triptans, serotonin agonists. Based on the vascular theory of the migraine pathophysiology, serotonin (5–HT) is depleted during a migraine attack. After that, blood vessels are diluted and a migraine attack occurs. Triptans suppress migraine attacks by contracting blood vessels and reducing the release of some substances associated with neuroinflammation such as CGRP. Triptans selectively act on 5–HT_1B and _1D receptors. However, Lasmiditan which selectively acts on 5–HT_1F receptor has developed. 5–HT_1D and _1F receptors are present in the trigeminal nerve peripheral terminal, while 5–HT_1B receptor is present in vascular smooth muscle. Therefore, 5–HT_1B has a vasoconstrictive effect. We cannot describe triptans to migraine patients with cardiovascular and cerebrovascular risks. However, 5–HT_1F receptor is present in the trigeminal nerve (Aδ fibers and C fibers), not in vascular smooth muscle. Then, lasmiditan has no vasoconstrictor effect, and it can be used for migraine patients who are contraindicated for triptans. In addition, unlike triptans, it passes through the blood–brain barrier, so it has the advantage that there is no need to worry about the timing of oral administration during a migraine attack.