Emerging Targets for Migraine Treatment

While understanding the pathophysiology of migraine has led to CGRP-based treatments, other potential targets have also been implicated in migraine.

To catalog new promising targets for the treatment of migraine.

We completed a literature review focusing on 5HT_1F, PACAP, melatonin, and orexins.

The 5HT_1F receptor agonist lasmiditan, following two positive randomized placebo-controlled trials, was FDA-approved for the acute treatment of migraine. PACAP-38 has shown analogous evidence to what was obtained for CGRP with its localization in key structures, provocation tests, and positive studies when antagonizing its receptor in animal models, although a PAC-1 receptor monoclonal antibody study was negative. Melatonin has undergone several randomized controlled trials showing a positive trend. Filorexant is the only dual orexin receptor antagonist, which was tested in humans with negative results.

Further and ongoing studies will determine the utility of these new therapies with lasmiditan and melatonin having demonstrated efficacy for the treatment of migraine.