DHE Pharmacology revisited: Does a broad receptor profile molecule treat the whole migraine?
posted in Presentations by Brooke Eger
Poster presented at the International Headache Congress HIS and EHF Joint Congress 2021, 8-12 September, 2021
Authors: Aurora S., RAY S., Satterly K., McConnachie L., Shrewsbury S., Hoekman J., Goadsby P.
Objectives: Migraine is a complex neurological disorder, however, therapeutics have focused on targeting a relatively narrow set of receptors i.e. 5HT1B/1D/F or CGRP. Comparative receptor pharmacology of various acute therapies for migraine were examined.
Methods: Following a literature review, additional, functional receptor activity of DHE was screened against 170 G-protein coupled receptors.
Results: DHE mesylate (10 μM) exhibited agonist activity at: Adrenoceptor α2B, CXCR7, Dopamine D2, D5, 5HT1A/1B/2A/2C/5A, binding with high affinity to the 5HT1B, Adrenoreceptor α2B, Dopamine D2receptors and exhibited antagonist activity at: Adrenoceptor a1B, a2A, a2C, CALCR-RAMP2, Dopamine D1, D3, D4, D5 and 5HT1F. Further work showed DHE did not bind to the 5HT3 receptor and did so in a limited capacity to the 5HT4E receptor, 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.
Conclusion: DHE interacts with several different receptor subtypes. Unlike other migraine therapeutics, it may exert a wider influence over the pathophysiology of the migraine. 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, perhaps, medication overuse headache.
Aurora S., RAY S., Satterly K., McConnachie L., Shrewsbury S., Hoekman J., Goadsby P. DHE Pharmacology revisited: Does a broad receptor profile molecule treat the whole migraine? International Headache Congress 8–12 September 2021. Cephalalgia. 2021;41(1_suppl):1-228. doi:10.1177/03331024211034005