Zolmitriptan nasal spray was developed specifically to achieve fast, high effectiveness and to overcome many of the limitations associated with oral and sc migraine therapies. Pharmacokinetic studies have demonstrated a very rapid appearance of zolmitriptan in plasma as early as 5 minutes after intranasal dosing, with about 40% of peak plasma concentration (C(max)) being achieved within 10 to 15 minutes of dosing. Comparison of plasma concentration-time profiles of zolmitriptan and its active metabolite after oral and intranasal administration, together with PET scanning, clearly indicate direct absorption of zolmitriptan across the nasal mucosa after intranasal administration. The remainder of the dose is then swallowed and is absorbed through the gastrointestinal tract. In one blinded, randomized, placebo-controlled, multiple-attack study of zolmitriptan nasal spray, headache response was superior to placebo as early as 15 minutes after dosing (p < 0.05). In the zolmitriptan 5 mg treatment group, the primary end point of 2-hour headache response was achieved in 70% (300/427) of attacks versus 31% of attacks (119/389 attacks) in the placebo group (p < 0.001). Patients achieved a 2-hour headache response, had no recurrence, and used no additional or escape medications for up to 24 hours in 49% of attacks versus 14% of attacks in the placebo group (p < 0.001). Zolmitriptan 5 mg nasal spray was well tolerated. These data and those from other similar studies demonstrate that zolmitriptan nasal spray combines early, sustained efficacy and good tolerability, making it an optimal acute treatment for migraine.