Lasmiditan: new drug for acute migraine

ABSTRACT

Migraine is ranked by the World Health Organization as the world’s second leading cause of disability. The current state of knowledge suggests that migraine is a neuronal process involving activation and sensitization of the trigeminal nociceptors and the trigeminocervical complex, as well as cortical spreading depression and abnormal brainstem activity. The present non vascular etiological basis has opened a new horizon in the treatment of acute migraine targeting the trigeminal pathways. Lasmiditan, a highly selective 5-HT1F receptor agonist, acts on the trigeminal system without causing vasoconstriction because of its low a?nity for 5-HT1B receptors. The compound belongs to a new class of drugs “ditans” and its mechanism of action is neuronal without evidence of vasoactive effects as seen with triptans. It lowers plasma protein extravasation decreasing the neurogenic inflammation of the dura and suppress neuronal firing within the trigeminal nucleus caudalis. Also, 5HT1F agonists have shown to decrease c-fos activity within trigeminal nucleus thereby reducing the level of synaptic activation. The onset of action of lasmiditan is fast, shows rapid absorption, oral bioavailability of 40% and linear pharmacokinetics. Most common adverse reactions seen are dizziness, paresthesia, somnolence, nausea, fatigue and lethargy with dizziness being the most recurrently reported adverse event. Clinical trials for lasmiditan to date have been positive, and maiden results suggest that lasmiditan may be a new safe and effective option for acute migraine treatment, especially for patients refractory to or unable to tolerate triptans, and/or for patients with pre-existing cardiovascular disease. With Eli Lilly and Co. having already applied for US FDA approval in Nov 2018, lasmiditan may soon be a new addition to the mounting armoury of drugs against migraine.