The conceptual shift of our understanding of migraine from a vascular disorder 
to a brain disorder has dramatically altered the approach to the development of 
new medicines in the field. Current pharmacologic treatments of acute migraine 
consist of nonspecific and relatively specific agents. Migraine-specific drugs 
comprise two classes, the ergot alkaloid derivatives and the triptans, serotonin 
5-HT(1B/1D) receptor agonists. The ergots, consisting of ergotamine and 
dihydroergotamine (DHE), are the oldest specific antimigraine drugs available 
and are considered relatively safe and effective. Ergotamine has been used less 
extensively because of its adverse effects; DHE is better tolerated. The triptan 
era, beginning in the 1990s, was a period of considerable change, although these 
medicines retained vasoconstrictor actions. New methods of delivering older 
drugs include orally inhaled DHE and the transdermal formulation of sumatriptan, 
both currently under study. Novel medicines being developed are targeted at 
neural sites of action. Serotonin 5-HT(1F) receptor agonists have proven 
effective in phase II studies and have no vascular actions. Calcitonin 
gene-related peptide (CGRP) receptor antagonists are another promising 
nonvasoconstrictor approach to treating acute migraine. Olcegepant (BIBN4096BS) 
and telcagepant (MK-0974) have been shown to be safe and effective in phase I, 
II, and (for telcagepant) phase III clinical trials. Other targets under 
investigation include glutamate (AMPA/kainate), TRPV1, prostanoid EP4, and 
nitric oxide synthase. With new neural targets and the potential for therapeutic 
advances, the next era of antimigraine medications is near.