Success and failure of triptans

Abstract

Sumatriptan and the newer triptans (zolmitriptan, naratriptan, rizatriptan, eletriptan, almotriptan, frovatriptan and donitriptan) display high agonist activity at 5-HT_1B and 5-HT_1D receptors. Most triptans, but not all (donitriptan, frovatriptan and rizatriptan), also have a high affinity at the 5-ht_1F receptor. In anaesthesisted animals, triptans decrease the arteriovenous anastomotic fraction of carotid blood flow. In isolated blood vessels, triptans cause contraction and this effect is more marked on cranial arteries. The 5-HT_1B receptors and not 5-HT_1D or 5-ht_1F receptors mediate the vascoconstrictor effect of triptans. In animal studies, the triptans exert an inhibitory effect within the trigeminovascular system. The therapeutic effect of triptans is mediated mainly by their cranial vasoconstrictor property. Whether the inhibitory effects of the triptans on the trigeminovascular system contribute to their efficacy in migraine is still a moot point. The biggest success of triptans is that they provide an excellent therapeutic option for migraine therapy. This success has generated awareness for migraine in patients, clinicians and researchers alike. This, in turn, has increased our knowledge of the disease pathophysiology, which will ultimately lead to even better drugs in future. Among the failures of triptans, one may mention that a minority of patients respond poorly and others may have headache recurrence and chest syndromes. Overall, however, the advantages of triptans far outweigh their disadvantages and they represent a significant advance in medical therapy.