The therapeutic pipeline in migraine: What does the future hold?

Migraine is one of the leading causes of disability globally. Despite advances in the available pharmacological options for its management, many patients still show a lack of response to these current therapeutics. As a consequence, it is important to explore new targets for the management of migraine and related headache disorders. In this review, we discuss evidence related to various novel targets that are in different stages of development as part of the current therapeutic pipeline in migraine management. These include recent studies that report the role of specific ion channels in migraine pathophysiology, including ATP-sensitive potassium channels (K_ATP), large conductance calcium- and voltage-activated potassium channels (BK_Ca), and transient receptor potential melastatin (TRPM) channels, specifically TRPM3 and TRPM8. Additionally, peptides secreted endogenously by hypothalamic nuclei have drawn attention, for example, oxytocin, orexins and prolactin have been signaled as possible systems for modulation with therapeutics. Here, we will assess preclinical validation studies, as well as clinical experimental and clinical trial data, and we will discuss some of the potential challenges with these targets and the future perspectives of these pipeline targets.