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Abstract Details

DHE Pharmacology Revisited: Does a broad receptor profile molecule treat the whole migraine?
Headache
Headache Posters (7:00 AM-5:00 PM)
065

Despite a growing body of science purporting migraine is a complex multifactorial brain network disease, therapeutics have increasingly focused on headache pain and targeting a very narrow set of receptors i.e. 5HT1B/1D/F or CGRP.  

To examine the comparative receptor pharmacology of various acute therapies for migraine. 

A literature review was conducted. Additionally, “state of the art” functional receptor activity of DHE was screened against 170 G-protein coupled receptors.

DHE (10 µM) exhibited agonist activity at the following receptors: Adrenoceptor α2B, CXCR7, Dopamine D2, D5, 5HT1A/1B/2A/2C/5A, binding with high affinity to the 5HT1B, Adrenoreceptor α2B, Dopamine D2receptors. DHE also exhibited antagonist activity at the following receptors: Adrenoceptor a1B, a2A, a2C, CALCR-RAMP2, Dopamine D1, D3, D4, D5 and 5HT1F. Further work showed DHE did not bind to 5HT3 and 4E receptors at concentrations up to 300 nM. Comparative receptor binding of migraine specific therapies is presented in tabular format. A model was created to show where in migraine progression each acute migraine specific therapeutic acts to address migraine symptoms.

DHE interacts with several different important receptor subtypes, unlike other migraine therapeutics, and therefore exerts a wider 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, extending duration of benefit, reducing headache recurrence rates and medication overuse headaches. Achieving dose-to-dose consistency and optimal plasma concentrations of DHE has been demonstrated to maximize therapeutic gain while safely addressing acute migraine. Advances in non-injected, non-oral delivery systems for DHE holds promise to achieve these goals.

Authors/Disclosures
Sheena K. Aurora, MD (Department of Neurology and Neurological Sciences)
PRESENTER
Dr. Aurora has received personal compensation for serving as an employee of Impel Neuropharma. Dr. Aurora has stock in Impel Neurpharma.
Sutapa Ray, PhD (Impel NeuroPharma) Dr. Ray has received personal compensation for serving as an employee of Impel Pharmaceuticals. Dr. Ray has stock in Impel Pharmaceuticals.
Kelsey Satterly Kelsey Satterly has received personal compensation for serving as an employee of Impel NeuroPharma . Kelsey Satterly has received intellectual property interests from a discovery or technology relating to health care.
Lisa McConnachie (Impel Neuropharma) Lisa McConnachie has received personal compensation for serving as an employee of Impel Neuropharma.
Stephen Bevan Shrewsbury, MD (Impel Pharmaceuticals) Dr. Shrewsbury has received personal compensation for serving as an employee of Impel NeuroPharma. Dr. Shrewsbury has received stock or an ownership interest from Impel NeuroPharma.
John *use 387100 Hoekman John Hoekman has received personal compensation for serving as an employee of Impel Neuropharma. John Hoekman has received stock or an ownership interest from Impel Neuropharma. John Hoekman has received intellectual property interests from a discovery or technology relating to health care.