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The serotonin receptor agonist triptan drugs (5-HT1B/1D receptor agonists) have been in use for over 20 years in the abortive management of migraine. Although clearly effective, their ability to produce vasoconstriction in cerebral and coronary arteries, thought to be mediated by their high affinity for the 5-HT1B receptor, has been a limitation to their use in certain patient populations. Variable potency triptan binding at the 5-HT1F receptor occurs in addition to binding at the 5-HT1B and 5-HT1D receptors. A more selective serotonin agonist without 5-HT1B-mediated vasoconstriction might prove efficacious yet safer. The 5-HT1F receptor has been targeted as a site of action for such a drug. In experimental models, 5-HT1F receptor agonists have been shown to block neurogenic inflammation and c-Fos expression in neural tissue and, as well, show no evidence of vasoconstriction in vascular tissue models in vitro. In clinical trials, efficacy in the abortive management of migraine has been established. Lasmiditan (LY573144), a selective 5-HT1F receptor agonist (K1=2.21 μM), showed efficacy in its primary endpoint, with a 2-hour placebo-subtracted headache response of 28.8%, though with frequent reports of dizziness, paresthesias, and vertigo. Study results support an emerging central neuronal mechanism of migraine pathophysiology. This review traces the history and use of 5-HT1F receptor agonists, now referred to as neurally acting anti-migraine agents in migraine management.

Emerging therapeutic options for acute migraine: focus on the potential of lasmiditan