DHE Pharmacology revisited: Does a broad receptor profile molecule treat the whole migraine?

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.

Citation:

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

Link: https://ihs-headache.org/wp-content/uploads/2021/09/IHC-2021-abstracts.pdf