What’s new in the treatment of acute migraine

With the rapid advances in the treatment of migraine attacks in the last few years, a number of non-specific anti-migraine drugs have been developed for clinical use. The most important class of drugs for the treatment of migraine attacks is represented by the triptans, which show 5-HT(1B/1D) receptor selectivity. Although their efficacy has been clearly demonstrated in controlled clinical trials and by meta-analyses, triptans are still far from being perfect drugs; they can potentially constrict human coronary arteries at therapeutic doses and therefore contraindications in the presence of cardiovascular disease remain the main limitation to their use. Another problem with these agents is the recurrence of moderate-to-severe pain within 24 h of initial headache relief. The mechanisms underlying the differences in headache recurrence have been elucidated in the last few years and reside in their pharmacological and pharmacokinetic properties. This prompted the development of new agents with selective agonistic effects for 5-HT(1D) and also 5-HT(1F) receptors without cardio- and cerebrovascular side effects. In initial clinical studies, the former were shown to be ineffective for migraine treatment, whereas the latter were demonstrated to be potentially useful for migraine attacks. However, the higher doses at which their effectiveness is exerted suggest that their main target at these doses is not the 5-HT(1F) receptors but mainly the 5-HT(1B) receptors, which seem to mediate the most important effect of all triptans, vasoconstriction of the cerebral vessels. Efforts have been made in recent years to develop other anti-migraine alternatives acting via the direct blockade of vasodilator mechanisms. They include calcitonin gene-related peptide (CGRP) receptor antagonists, capsaicin/vanilloid receptor agonists, adenosine A1 agonists and cannabinoid analogues acting on CB1 receptors, antagonists at 5-HT(7) receptors and inhibitors of nitric oxide biosynthesis. These alternatives will hopefully be effective in treating migraine attacks and lead to fewer side effects. The first promising clinical results in this regard were recently obtained for the highly specific and potent CGRP antagonist, BIBN 4096 BS.