K K Jain MD (Dr. Jain is a consultant in neurology and has no relevant financial relationships to disclose.)
Originally released February 23, 1999; last updated January 23, 2020; expires January 24, 2023

This article includes discussion of dihydroergotamine, DHE, and Migranal. The foregoing terms may include synonyms, similar disorders, variations in usage, and abbreviations.

Historical note and terminology

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. Dihydroergotamine mesylate has been used as an acute migraine treatment since 1945, but tolerability of intravenous administration limited its use. 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. There is renewed interest in dihydroergotamine, and the need for nonoral, noninjected delivery is now being pursued further (Silberstein et al 2020).

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