Editing Triptan (section)

== History ==
{{further|Discovery and development of triptans}}
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 early 1950s it was confirmed that both substances were the same. In the mid-1950s it was proposed that serotonin had a role as a [[neurotransmitter]] in the central nervous system (CNS) of animals. Investigations of the mechanism of action were not very successful as experimental techniques were lacking.<ref name="Foyes">{{cite book|author=Lippincott, W. W. |author2=Lemke, T. L. |author3=Williams, D. A. |author4=Roche, V. F. |author5=Zito, S. W. |year=2013|title=Foye's Principles of Medicinal Chemistry|publisher=Lippincott Williams & Wilkins|pages=368–376}}</ref>

Later in the 1960s, studies showed that [[vasoconstriction]] caused by 5-HT, [[noradrenaline]] and [[ergotamine]] could reduce migraine attacks. Patrick P.A. Humphrey among others at [[Glaxo]] started researching the 5-HT receptor to discover a more direct 5-HT [[agonist]] with fewer side effects.

They continued developing and working on a desirable action on 5-HT by 5-HT<sub>1</sub> receptor activation for an anti-migraine drug. Continued work led to the [[Drug development|development]] of sumatriptan, now known as the first 5-HT<sub>1</sub> agonist, selective for the 5-HT<sub>1D/B</sub> receptors and also the 5-HT<sub>1F</sub> receptor with less affinity. By 1991 sumatriptan became available in clinical use in the Netherlands and in the US in 1993. However, there was always a debate about its mechanism of action, and it still remains unclear today. Later, Mike Moskowitz proposed a theory about "neuronal extravasation", and this was the first clue that sumatriptan might have a direct [[neuronal]] effect in migraine attacks.<ref>{{cite journal | last1 = Humphrey | first1 = P. P. | year = 2007 | title = The discovery of a new drug class for the acute treatment of migraine | doi = 10.1111/j.1526-4610.2007.00672.x | pmid = 17425704 | journal = Headache | volume = 47 | issue = Suppl 1| pages = S10–19 | s2cid = 12201740 | doi-access = free }}</ref>

Sumatriptan became a prototype for other triptans that have been developed for improved selectivity for the 5-HT<sub>1D/B</sub> receptors.<ref name="Foyes" />