The shift in our understanding of
migraine as a vascular disorder to a
brain disorder has opened new avenues for the development of novel
therapeutics with neural targets. The advent of 5-HT1B/1D receptor agonists, the
triptans, in the 1990s was a crucial step in the modern evolution of treatment. The use of
triptans, like their predecessors, is limited by their
vasoconstrictor effects, and new development has been slowed by poor academic research funding to identify new targets. The development of agents without vascular effects, such as
calcitonin gene-related peptide receptor antagonists and selective
serotonin 5-HT1F receptor agonists, will bring more effective treatments to a population currently without
migraine-specific options. In addition, advances in understanding
migraine pathophysiology have identified new potential pharmacologic targets such as
acid-sensing ion channels,
glutamate and
orexin receptors,
nitric oxide synthase (NOS), and transient receptor potential (TRP) channels. Although previous attempts to block subtypes of
glutamate receptors, NOS, and TRP channels have had mixed outcomes, new molecules for the same targets are currently under investigation. Finally, an entirely new approach to
migraine treatment with noninvasive neuromodulation via transcutaneous neurostimulation or
transcranial magnetic stimulation is just beginning. Hopefully in the coming years we will see a new era of
migraine therapy, with multiple classes of better-tolerated, more effective agents targeting diverse yet specific
migraine mechanisms.