Is lasmiditan the next big thing in the fight against migraine?

Serotonin receptor targeted therapy for migraine treatment: an overview of drugs in phase I and II clinical development

Barbanti P, Aurilia C, Egeo G, Fofi L, Palmirotta R.

Expert Opin Investig Drugs 2017; 26:269-277.

Abstract

Background:

Research has focused on serotonin (5-HT) 5-HT1D and 5-HT1F receptors to develop drugs acting through non-vasoconstrictive mechanisms for treating acute migraine and those targeting 5-HT2B and 5-HT7 receptors for preventing migraine.

Methods:

This paper reviews antimigraine drugs targeting 5-HT receptors in one phase I trial (sumatriptan iontophoretic transdermal system, TDS) and five phase II clinical trials (PNU-142633, LY334370, lasmiditan, NOX-188).

Expert opinion:

Data from our overview on investigational drugs in phase I and II clinical trials using the 5-HT1B/1D receptor agonist (sumatriptan TDS), 5-HT1D receptor agonist (PNU-142633), 5-HT1F receptor agonists (LY334370, lasmiditan) and a combined 5-HT1B/1D receptor agonist with nNOS inhibition (NOX-188) provided encouraging data for sumatriptan TDS and lasmiditan, disappointing results for PNU-142633, and promising findings for NOX-188.

Conclusion:

The 5-HT1F receptor agonist lasmiditan, a drug acting through non-vasoconstrictive mechanisms, represents a promising safe, effective and tolerated acute migraine therapy also for patients at cardiovascular risk. Upcoming phase III trials should clarify the optimal lasmiditan dose and eventual clinical advantages over triptans. The negative results for the PNU-142633 trial prompt further studies using specific compounds more precisely targeting 5-HT1D receptors. Antagonism at 5-HT2B and 5-TH7 receptors, a promising strategy to prevent migraine, is still limited to experimental migraine models.

The following are related papers:

Capi M, de Andrés F, Lionetto L, Gentile G, et al. Lasmiditan for the treatment of migraine. Expert Opin Investig Drugs 2017; 26:227-234.

Raffaelli B, Israel H, Neeb L, Reuter U. The safety and efficacy of the 5-HT 1F receptor agonist lasmiditan in the acute treatment of migraine. Expert Opin Pharmacother 2017; doi: 10.1080/14656566.2017.1361406 (Epub ahead of print).

These references are all cited in the neurochecklist:

Migraine: drug prophylaxis

Abstract link 1

Abstract link 2

Abstract link 3

Visual disturbance: attempt at portraying a migraine. Stinging Eyes on Flikr. https://www.flickr.com/photos/martinlatter/4625605348
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