The role of serotonin (5HT) in migraine is recognized to be the cornerstone for the currently available therapeutic options namely ergot alkaloids and triptans. The role of mediators such as Calcitonin Gene-Related Peptide (CGRP), nitric oxide and excitatory neurotransmitter glutamate, has been realized and ignited the development of drugs targeting these factors. Having a group of drugs with a nonvascular mechanism of action, devoid of unwanted effects with a different spectrum of indication and contraindications, is the need of the hour to expand the armamentarium available to tackle acute migraine attack. (Xavier et al, 2017)
Novel anti-migraine drugs target CGRP signaling through either stimulation of 5-HT1F receptors on trigeminovascular nerves (resulting in inhibition of CGRP release) or direct blockade of CGRP or its receptor. Lasmiditan is a highly selective 5-HT1F receptor agonist and, unlike the triptans, is devoid of vasoconstrictive properties, allowing its use in patients with cardiovascular risk. (de Vries et al, 2020) While this class of medication works similarly to triptans, it selectively targets 5-HT1F receptors, and does not cause vasoconstriction. Lasmiditan is the first medication in this class and has demonstrated statistically significant efficacy similar to triptans in 2 phase 3 clinical trials. (Mathew, 2019)
Lasmiditan is a small molecule selective agonist of the serotonin 1F [5HT1F] receptor which decreases neuron activity that is thought to mediate pain and inflammation associated with migraine headaches. In clinical trials, lasmiditan was found to shorten the duration of migraine headache pain and other associated symptoms. Lasmiditan is generally well tolerated and has been associated with only rare instances of transient serum aminotransferase elevations during therapy but with no instances of clinically apparent liver injury. (Livertox, 2021)
US FDA approved lasmiditan 50 mg and 100 mg tablets for the acute treatment of migraine with or without aura in adults. Is not for use in the preventive treatment of migraine. (Lamb, 2019)
Xavier AS, Lakshmanan M, Gunaseelan V. The Journey of the Non-Vascular Relief for Migraine: From 'Triptans' To 'Ditans'. Curr Clin Pharmacol. 2017;12(1):36-40. doi: 10.2174/1574884712666170419155048. PMID: 28425871.
de Vries T, Villalón CM, MaassenVanDenBrink A. Pharmacological treatment of migraine: CGRP and 5-HT beyond the triptans. Pharmacol Ther. 2020 Jul;211:107528. doi: 10.1016/j.pharmthera.2020.107528. Epub 2020 Mar 12. PMID: 32173558.
Mathew PG, Klein BC. Getting to the Heart of the Matter: Migraine, Triptans, DHE, Ditans, CGRP Antibodies, First/Second-Generation Gepants, and Cardiovascular Risk. Headache. 2019 Sep;59(8):1421-1426. doi: 10.1111/head.13601. Epub 2019 Jul 18. PMID: 31318457.
LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012–. Lasmiditan. 2021 Jul 20. PMID: 34324283.
Lamb YN. Lasmiditan: First Approval. Drugs. 2019 Dec;79(18):1989-1996. doi: 10.1007/s40265-019-01225-7. PMID: 31749059.