DOES DHE TREAT THE WHOLE MIGRAINE?

Authors: Authors: Aurora SK, Ray S, Satterly KH, Shrewsbury SB, Hoekman J

Affiliations: 1. Impel NeuroPharma, Seattle WA

Objective:
Review the receptor pharmacology of different migraine abortive agents.

Introduction:
Migraine is now recognized as a complex, multifactorial brain network disease associated with 40 different gene loci. Despite a growing body of scientific evidence about the spectrum of migraine pathophysiology including the autonomic dysfunction, advances in migraine therapeutics have focused on headache pain, targeting a very narrow set of receptors i.e. 5HT1B/D or F or CGRP.  Migraine however encompasses a spectrum of symptoms i.e. premonitory phase, aura, photo-, phono- and osmo-phobia as well as a postdrome.

Receptor pharmacology data may provide insight into the benefits throughout the migraine cycle of using a broad receptor binding agent such as DHE, versus the limitations of treating with a narrowly targeted therapy. This may further explain why DHE is so effective even in the most difficult to treat migraines.

Methods:
A literature review was conducted to compare the pharmacology and biological activity of new and existing migraine specific treatments.

Results:
Comparative receptor binding of current and new migraine specific therapies is presented in tabular format. A model was created to show where in migraine progression each therapeutic acts to address which migraine symptoms.

Conclusion:
Unlike other migraine therapeutics, DHE interacts with several different receptor families and subtypes and therefore is able to exert a greater influence over the pathophysiology of the migraine cycle (premonitory thirst, aura, allodynia, hypersensitivity, withdrawal, ictal pain, vasoconstriction, central sensitization, postdrome and interictal period). Moreover, the slow dissociation of DHE from target receptors is thought to sustain its anti-migraine effects reducing headache recurrence and potential medication overuse. Dose-to-dose consistency and optimal plasma concentrations of DHE maximize therapeutic gain while providing safety and tolerability in addressing acute migraine. Advances in delivery systems for DHE make this possible.

Author Contact
Sheena K Aurora saurora@impelnp.com
Sutapa Ray sray@impelnp.com
Kelsey H Satterly ksatterly@impelnp.com
Stephen B Shrewsbury sshrewsbury@impelnp.com
John Hoekman jhoekman@impelnp.com

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