Can we develop neurally acting drugs for the treatment of migraine?

Serotonin (5-HT)(1B/1D) receptor agonists, which are also known as triptans, represent the most important advance in migraine therapeutics in the four millennia that the condition has been recognized. The vasoconstrictive activity of triptans produced a small clinical penalty in terms of coronary vasoconstriction but also raised an enormous intellectual question: to what extent is migraine a vascular problem? Functional neuroimaging and neurophysiological studies have consistently developed the theme of migraine as a brain disorder and, therefore, demanded that the search for neurally acting antimigraine drugs should be undertaken. The prospect of non-vasoconstrictor acute migraine therapies, potential targets for which are discussed here, offers a real opportunity to patients and provides a therapeutic rationale that places migraine firmly in the brain as a neurological problem, where it undoubtedly belongs.