neurogenic inflammation upon administration with sumatriptan and other related compounds that act on prejunctional 5-HT1D receptors. All triptans, like the older drug dihydroergotamine, have agonistic effects on the 5-HT1D receptor. Comparison of sumatriptan and dihydroergotamine showed that dihydroergotamine has high affinity and sumatriptan has medium affinity for 5-HT1D. Triptans have at least three modes of action. These antimigraine mechanisms are: vasoconstriction of pain producing intra cranial extracerebral vessels by a direct effect on vascular smooth muscle. Sumatriptan and rizatriptan have been shown to cause vasoconstriction in the human middle meningeal arteries. inhibition of vasoactive neuropeptide release by trigeminal terminals innervating intracranial vessels and the dura mater. The trigeminocervical complex has 5-HT1D receptors that bind dihydroergotamine and triptans in humans. Rizatriptan has been shown to block dural vasodilation and plasma protein extravation by inhibiting the release of CGRP via activation of receptors on preganglionic trigeminal sensory nerver terminals. Sumatriptan is shown to inhibit potassium stimulated CGRP secretion from cultured trigeminal neurons in dose dependant manner and may also inhibit the release of substance P. inhibition of nociceptive neurotransmission within the trigeminocervical complex in the brainstem and upper cervical spinal column. Rizatriptan has central trigeminal antinociceptive activity. Other possibilities of triptans in antimigraine effects are modulation of nitric oxide dependent signal transduction pathways, nitric oxide scavenging in the brain, and sodium dependent cell metabolic activity. Pharmacokinetics Triptans have a wide variety of pharmacokinetic properties. Bioavailability is between 14% and 70%, biological half-life (T1/2) is between 2 and 26 hours. Their good ability to cross the blood–brain barrier and the rather long half life of some triptans may result in lower frequencies of migraine recurrence. Comparison Zolmitriptan is different from the other triptans because it is converted to an active N-desmethyl metabolite which has higher affinity for the 5-HT1D and 5-HT1B receptors; both substances have a biological half-life of 2 to 3 hours. In studies, newer triptans are mostly compared to sumatriptan. They are better than sumatriptan for their longer half-life in plasma and higher oral bioavailability, but have a higher potential for central nervous side effects. Donitriptan and avitriptan were never marketed. History The history of triptans began with the proposed existence of then unknown serotonin (5-hydroxytryptamine, 5-HT). In the late 1940s two groups of investigators, one in Italy and the other in the United States, identified a substance that was called serotonin in the US and enteramine in Italy. In the