Acute migraine therapy: The newer drugs

In 1996, our knowledge of acute antimigraine therapy expanded in three major areas. First, large surveys have confirmed the remarkable efficacy profile of sumatriptan in clinical practice. No satisfying clinical, pharmacokinetic or genetic explanations were found for its major shortcomings: nonresponders, headache recurrence and noncardiac chest symptoms. Second, the novel 5-HT1B/D agonists zolmitriptan (311C90), rizatriptan (MK-462), eletriptan (UK-116,044), avitriptan (EMS-180048) and alniditan (R091274) were all proved superior to placebo for attack treatment, but their advantages over sumatriptan are yet to be analysed in more detail. A higher lipophilicity explains (except for alniditan) their greater oral bioavailability and better central nervous system penetration. A central action now proved experimentally in animals and in humans for 5-HT1B/D agonists such as zolmitriptan may be advantageous for the antimigraine efficacy, but it could also increase sedation. Third, an endothelin (Ro470203, bosentan) and a neurokinin 1 (RPR100893) receptor antagonist were found to be ineffective in migraine. Both compounds are potent inhibitors of neurogenic plasma extravasation in rat dura mater, which might suggest that this pharmacological property does not necessarily predict efficacy in aborting migraine attacks.