Overview of Triptans in the Treatment of Acute Migraine

The advent of triptans for effective relief of migraine represented a therapeutic breakthrough. Triptans are serotonin (5-hydroxytryptamine, or 5-HT) agonists with high affinity for 5-HT 1B and 5-HT 1D receptors. There are, at present, seven commonly used triptans: almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan, and zolmitriptan. Some controversy still surrounds the mode of action of this class. When first studied, it was thought that triptans provided relief from migraine through cranial vasoconstriction, probably via action at postsynaptic 5-HT 1B receptors on the smooth-muscle cells of blood vessels. More recently, however, triptans have also been demonstrated to block release of vasoactive peptides from the perivascular trigeminal neurons owing to their action at presynaptic 5-HT 1D receptors on the nerve terminal. Triptans may also facilitate descending pain inhibitory systems. However, it is not certain whether or not the activation of vascular 5-HT 1B receptors is essential for relieving migraine. Many drug characteristics need to be taken into account when selecting the best triptan for an individual patient. Clinical characteristics of the migraine attack and the patient’s lifestyle and medical history are also important. Despite their biochemical similarity, triptans have distinct pharmacokinetic and pharmacodynamic profiles. Frovatriptan and naratriptan, for example, have a longer half-life and therefore a delayed onset of action and prolonged duration compared with the other triptans, which are fast acting, with a rapid dose-dependent efficacy and higher risk of adverse events and migraine recurrence. Migraine recurrence is affected by the pharmacological and pharmacokinetic properties of the triptan but is unrelated to initial clinical efficacy. Triptans with a longer half-life and largest 5-HT 1B receptor affinity have the lowest rates of headache recurrence.