Seeking the best care for acute migraine

Abstract

In recent years, we have seen exciting advances in the knowledge of mechanisms that underlie migraine. These have thus promoted investigations into new drugs for the management of acute migraine. The major goal in migraine research is to identify and study non-vascular targets for migraine therapy. The 5-HT 1F neuronal receptor is apparently not involved in the vascular effects of triptans. Clinical evaluation of LY33470, a potent agonist of 5-HT 1F receptors, has demonstrated that the drug is effective in ending a migraine attack. These results suggest that 5-HT 1F receptor agonists may represent new antimigraine drugs without cerebrovascular or cardiovascular effects. From the plasma extravasation model of migraine, potential therapeutic targets were identified, although in testing no effects were observed: endothelin and substance P antagonists and the specific serotonin agonist CP 122,288, potent inhibitors of neurogenic inflammation, were ineffective in the treatment of a migraine attack. Since a causative role of CGRP in migraine has been postulated, novel antimigraine drugs include CGRP antagonists. Molecules with highly selective antagonistic action on human CGRP receptors of cerebral circulation have been discovered. These CGRP antagonists are in preclinical and clinical trials and the results are awaited with great interest. In addition, a small pilot study found civamide, a capsaicin derivative which causes CGRP depletion from trigeminal sensory fibers, to be effective in the migraine attack. Both NMDA and non-NMDA receptors for glutamate and related excitatory aminoacids are found on trigeminal neurons; therefore excitatory aminoacid receptor antagonists may provide therapeutic action in migraine. Recently, a glutamate receptor antagonist (LY293558) that had not shown vascular effects in animal models demonstrated an antimigraine effect. More specific compounds are also warranted in confirming nitric oxide inhibition as a therapeutic approach in migraine. Thus, it is likely that in the near future emerging therapies will increasingly meet patients' and physicians' goals.