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Serotonin receptor agonists in the acute treatment of migraine: a review on their therapeutic potential

Authors Negro A, Koverech A, Martelletti P

Received 14 November 2017

Accepted for publication 16 January 2018

Published 8 March 2018 Volume 2018:11 Pages 515—526

DOI https://doi.org/10.2147/JPR.S132833

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Minal Joshi

Peer reviewer comments 2

Editor who approved publication: Dr E Alfonso Romero-Sandoval


Andrea Negro,1,2 Angela Koverech,2,3 Paolo Martelletti1,2

1Department of Clinical and Molecular Medicine, Sapienza University, Rome, Italy; 2Department of Internal and Emergency Medicine, Regional Referral Headache Centre, Sant’Andrea Hospital, Rome, Italy; 3Department of Physiology and Pharmacology “Vittorio Erspamer”, Sapienza University, Rome, Italy

Abstract: Migraine is an important socioeconomic burden and is ranked the sixth cause of years of life lost because of disability in the general population and the third cause of years of life lost in people younger than 50 years. The cornerstone of pharmacological treatment is represented by the acute therapy. The serotonin (5-hydroxytryptamine [5-HT]) receptor subtype 1B/1D agonists, called triptans, are nowadays the first-line acute therapy for patients who experience moderate-to-severe migraine attacks. Unfortunately, a high percentage of patients are not satisfied with this acute treatment, either for lack of response or side effects. Moreover, their mechanism of action based on vasoconstriction makes them unsuitable for patients with previous cardio- and cerebrovascular diseases and for those with uncontrolled hypertension. Since the introduction of triptans, no other acute drug class has passed all developmental stages. The research for a new drug lacking vasoconstrictive effects led to the development of lasmiditan, a highly selective 5-HT1F receptor agonist with minimized interactions with other 5-HT receptor subtypes. Lasmiditan is considered to be the first member of a new drug category, the neurally acting anti-migraine agent (NAAMA). Phase II and III trials had shown superiority compared to placebo and absence of typical triptan-associated adverse events (AEs). Most of the AEs were related to the central nervous system, depending on the high permeability through the blood–brain barrier and mild to moderate severity. The results of ongoing long-term Phase III trials will determine whether lasmiditan will become available in the market, and then active triptan comparator studies will assess patients’ preference. Future studies could then explore the safety during pregnancy and breastfeeding or the risk that overuse of lasmiditan leads to medication overuse headache.

Keywords: migraine, acute treatment, lasmiditan, 5-HT1F agonists

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