Emerging drugs in migraine treatment

Ergot alkaloids have been the mainstay of acute migraine therapy for most of the 20th century. They have been supplanted by sumatriptan-like drugs ('triptans'), which, while keeping some of the ergots' mechanisms of action, show improved safety profiles due to their increased receptor selectivity. However, triptans are still far from being perfect drugs: they can constrict human coronary arteries at therapeutic doses and, therefore, are contra-indicated in the presence of cardiovascular disease. Another problem with these agents is recurrence of moderate-to-severe pain within 24 h of initial headache relief. While mechanism-driven drug design has led to the development of various novel, albeit still imperfect, acute antimigraine medications, only a few new prophylactic agents have been made available to migraine clinicians. The efficacy of most, if not all of them has been discovered serendipitously. This is probably due to the fact that, while the pathophysiology of a migraine attack is now reasonably understood, the mechanisms leading to an attack are still mostly unknown. This update analyses the profile of some antimigraine drugs in clinical trials, their mode of action and their potential advantages or drawbacks over already available agents.