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

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.

Anti-Migraine Effect of the Herbal Combination of Chuanxiong Rhizoma and Cyperi Rhizoma and UPLC-MS/MS Method for the Simultaneous Quantification of the Active Constituents in Rat Serum and Cerebral Cortex

“…5-HT is widely accepted as a contributor to migraine. 5-HT releases in the early prodromal phase of a migraine attack, subsequently, 5-HT is metabolized to 5-HIAA in the ictal phase [35]. Migraine patients have a low plasma and cerebral 5-HT level between attacks [36].…”

Lasmiditan for the treatment of acute migraine: a review and potential role in clinical practice

“…The AUC(0-t) and AUC(0-inf) were higher in the fed (2,244 ng.h/mL, 2,265 ng.h/mL) than the fasted states (1,892 ng.h/mL, 1,906 ng.h/mL) respectively. 15 It is not known whether the differences observed in the fed and fasted states have clinical significance.…”

Vestibular Neuroscience for the Headache Specialist

“…Triptans are 5‐HT 1B , 5‐HT 1D , and at times 5‐HT 1F agonists. Ditans selectively bind to the 5‐HT 1F subtype and are being evaluated in clinical trials . Lasmiditan has a high incidence of dizziness and vertigo (dose‐dependent, relative to placebo); which may reflect an effect of 5‐HT 1F activation on vestibular function.…”