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Pharmaceuticals
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Migraine: Experimental Models and Novel Therapeutic Target
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Migraine: Experimental Models and Novel Therapeutic Target

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Pharmacology".

Deadline for manuscript submissions: closed (15 August 2023) | Viewed by 10905

Special Issue Editors

Dr. Sarah Louise Tangsgaard Christensen

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Guest Editor
Danish Headache Center, Department of Neurology, Copenhagen University Hospital-Rigshospitalet, 2600 Glostrup, Denmark
Interests: animal models; behaviour; experimental migraine; trigeminovascular system
Prof. Dr. Jes Olesen

E-Mail Website
Guest Editor
Danish Headache Center, Department of Neurology, Copenhagen University Hospital - Rigshospitalet, 2600 Glostrup, Denmark
Interests: Migraine classification; migraine pathophysiology; drug targets

Special Issue Information

Dear Colleagues,

Out of all diseases, migraines are the second most disabling, and more than one billion persons worldwide have migraines. Nevertheless, migraine research has been grossly underfunded and the interest in migraines from the pharmaceutical industry has been limited. All of this has now changed with the advent of a number of new drugs antagonizing the naturally occurring signalling molecule calcitonin gene-related peptide (CGRP). This is the first mechanism-based drug development for migraines, and it illustrates how basic research in human and animal models of migraines can identify valuable novel drug targets. The topic of the present Special Issue is therefore very timely. There are already many validated human and animal experimental models, and this Special Issue brings together our knowledge about them. It provides a stepstone for further advances in experimental migraine research. Experimental research has already identified several migraine mechanisms that are promising drug targets. However, knowledge of them is, to a large extent, limited to the research groups responsible for the research. In this Special Issue, the models and derived drug targets are comprehensively described in one volume. Combined with the projected enormous size of the migraine drug market the information in this Special Issue will hopefully stimulate the pharma industry to pay much more attention to migraine in the future. The unserved need is immense.

Dr. Sarah Louise Tangsgaard Christensen
Prof. Dr. Jes Olesen
Guest Editors

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceuticals is an international peer-reviewed open access monthly journal published by MDPI.

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Keywords

  • Migraine
  • pathofysiology
  • translational research
  • drug targets
  • human models
  • animal models

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Published Papers (2 papers)

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Research

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10 pages, 1283 KiB  
Article
Blocking the CGRP Receptor: Differences across Human Vascular Beds
by Tessa de Vries, Deirdre M. Boucherie, Antoon van den Bogaerdt, A. H. Jan Danser and Antoinette MaassenVanDenBrink
Pharmaceuticals 2023, 16(8), 1075; https://doi.org/10.3390/ph16081075 - 28 Jul 2023
Cited by 4 | Viewed by 2026
Abstract
Multiple drugs targeting the calcitonin gene-related peptide (CGRP) receptor have been developed for the treatment of migraine. Here, the effect of the small-molecule CGRP receptor antagonist zavegepant (0.1 nM–1 µM) on CGRP-induced relaxation in isolated human coronary arteries (HCAs) was investigated. A Schild [...] Read more.
Multiple drugs targeting the calcitonin gene-related peptide (CGRP) receptor have been developed for the treatment of migraine. Here, the effect of the small-molecule CGRP receptor antagonist zavegepant (0.1 nM–1 µM) on CGRP-induced relaxation in isolated human coronary arteries (HCAs) was investigated. A Schild plot was constructed and a pA2 value was calculated to determine the potency of zavegepant. The potency and Schild plot slopes of atogepant, olcegepant, rimegepant, telcagepant, ubrogepant and zavegepant in HCAs and human middle meningeal arteries (HMMAs), obtained from our earlier studies, were compared. Zavegepant shifted the concentration–response curve to CGRP in HCAs. The corresponding Schild plot slope was not different from unity, resulting in a pA2 value of 9.92 ± 0.24. No potency difference between HCAs and HMMAs was observed. Interestingly, olcegepant, atogepant and rimegepant, with a Schild plot slope < 1 in HCAs, were all >1 log unit more potent in HMMAs than in HCAs, while telcagepant, ubrogepant and zavegepant, with a Schild plot slope not different from unity, showed similar (<1 log difference) potency across both tissues. As a Schild plot slope < 1 may point to the involvement of multiple receptors, it is important to further identify the receptors involved in the relaxation to CGRP in HCAs, which may be used to improve the cardiovascular safety of future antimigraine drugs. Full article
(This article belongs to the Special Issue Migraine: Experimental Models and Novel Therapeutic Target)
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Review

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19 pages, 3773 KiB  
Review
A Scoping Review and Meta-Analysis of Anti-CGRP Monoclonal Antibodies: Predicting Response
by Ja Bin Hong, Kristin Sophie Lange, Lucas Hendrik Overeem, Paul Triller, Bianca Raffaelli and Uwe Reuter
Pharmaceuticals 2023, 16(7), 934; https://doi.org/10.3390/ph16070934 - 27 Jun 2023
Cited by 31 | Viewed by 8523
Abstract
Calcitonin gene-related peptide-targeted monoclonal antibodies (CGRP mAbs) are increasingly being used as preventive treatments for migraine. Their effectiveness and safety were established through numerous randomized placebo-controlled trials and real-world studies, yet a significant proportion of patients do not respond to this treatment, and [...] Read more.
Calcitonin gene-related peptide-targeted monoclonal antibodies (CGRP mAbs) are increasingly being used as preventive treatments for migraine. Their effectiveness and safety were established through numerous randomized placebo-controlled trials and real-world studies, yet a significant proportion of patients do not respond to this treatment, and currently, there is a lack of accepted predictors of response to guide expectations, as data from studies so far are lacking and inconsistent. We searched Embase and MEDLINE databases for studies reporting on predictors of response to CGRP and/or CGRP-receptor (CGRP-R) mAbs, defined as a 30% or 50% reduction in monthly headache or migraine days at varying durations of follow-up. Quantitative synthesis was performed where applicable. We found 38 real-world studies that investigated the association between various predictors and response rates. Based on these studies, good response to triptans and unilateral pain with or without unilateral autonomic symptoms are predictors of a good response to CGRP(-R) mAbs. Conversely, obesity, interictal allodynia, the presence of daily headaches, a higher number of non-successful previous prophylactic medications, and psychiatric comorbidities including depression are predictive of a poor response to CGRP(-R) mAbs. Future studies should confirm these results and help to generate more tailored treatment strategies in patients with migraine. Full article
(This article belongs to the Special Issue Migraine: Experimental Models and Novel Therapeutic Target)
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