Ergotamine, originally derived from a rye fungus (Claviceps purpurea) and isolated in 1918, was reported to be an effective antimigraine agent in 1925 in Switzerland (Tfelt-Hansen and Koehler 2008). However, absorption of this compound is erratic by oral or rectal routes, and side effects such as nausea, vomiting, and peripheral vasoconstriction are common. Ergotism can result from prolonged, excessive use. The search for a safer compound led to the development of a dehydrogenated derivative of ergotamine, dihydroergotamine as an adrenolytic agent in 1943. This was first available, in the inconvenient form of intramuscular injection, for treatment of acute migraine. Further clinical trials were conducted for dihydroergotamine administration by nasal spray in the early 1990s. The nasal spray was approved by the United States Food and Drug Administration in 1998.