Orally Inhaled Dihydroergotamine

Reviving and Improving a Classic

Eric P Baron; Stewart J Tepper

Disclosures

Future Neurology. 2011;6(3):327-333. 

In This Article

Abstract and Introduction

Abstract

Migraine pathophysiology continues to evolve, and additional therapeutic receptors influencing unrecognized neural networks within the cortex, brainstem and cerebral vasculature likely exist. Following the advent of the triptans, the use of dihydroergotamine (DHE) declined, because of the ease of use and improved side effect profiles of triptans. However, there remain many patients who respond poorly to triptans, yet respond significantly better to DHE. This may be due to the broader neuroreceptor targets that DHE interacts with, as opposed to the selective receptor activity of the triptans. Unfortunately, DHE is still infrequently utilized compared with other acute treatments such as triptans, primarily because of difficulty in administration and physician unfamiliarity and inexperience with its use. However, the new orally inhaled DHE appears to be as effective with a better side effect profile compared with intravenous DHE, thus eliminating the complexities typically associated with DHE administration.

Introduction

Throughout history, a multitude of refined ergot-based medications have been developed, including bromocriptine, pergolide, ergotamine tartrate, methylergonovine, methysergide and dihydroergotamine (DHE), all of which are derived from the fungus Claviceps purpurea. Historical and clinical reviews of these medications are available.[1,2] DHE is a semisynthetic ergot alkaloid that was first synthesized by hydrogenation of an unsaturated double bond at the 9–10 position of the ergoline ring in ergotamine by Stoll and Hofmann in 1943.[2,3] Notably, Albert Hofmann was the Swiss scientist best known as the first person to accidentally synthesize, ingest and describe the psychedelic effects of another infamous ergot derivative, lysergic acid diethylamide (LSD). DHE was shown to have greater α-adrenergic antagonist activity, reduced vasoconstrictor activity and reduced emesis compared with ergotamine.[2] Thus, it was initially introduced as an adrenolytic agent in 1943 with the surprising goal of being an antihypertensive medication.[2] However, it was later shown to raise blood pressure slightly and to be very effective in migraine, and was first used to treat migraine in 1945.[2,4] It remains marketed in Europe as an oral treatment, despite its poor absorption, as a medication to increase blood pressure. Subsequent studies have confirmed its effectiveness in episodic[5] and intractable migraine, especially in repetitive intravenous (IV) use as per Raskin's protocol.[6]

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