Tehran University of Medical Sciences

Science Communicator Platform

Stay connected! Follow us on X network (Twitter):
Share By
Future Targets for Migraine Treatment Beyond Cgrp Publisher Pubmed



Alhassany L1 ; Boucherie DM1 ; Creeney H2 ; Van Drie RWA1, 3 ; Farham F4 ; Favaretto S5 ; Gollion C6 ; Grangeon L7 ; Lyons H8 ; Marschollek K9 ; Onan D10, 11 ; Pensato U12, 13 ; Stanyer E2 ; Waliszewskaprosol M9 Show All Authors
Authors
  1. Alhassany L1
  2. Boucherie DM1
  3. Creeney H2
  4. Van Drie RWA1, 3
  5. Farham F4
  6. Favaretto S5
  7. Gollion C6
  8. Grangeon L7
  9. Lyons H8
  10. Marschollek K9
  11. Onan D10, 11
  12. Pensato U12, 13
  13. Stanyer E2
  14. Waliszewskaprosol M9
  15. Wiels W14
  16. Chen HZ2
  17. Amin FM15, 16

Source: Journal of Headache and Pain Published:2023


Abstract

Background: Migraine is a disabling and chronic neurovascular headache disorder. Trigeminal vascular activation and release of calcitonin gene-related peptide (CGRP) play a pivotal role in the pathogenesis of migraine. This knowledge has led to the development of CGRP(-receptor) therapies. Yet, a substantial proportion of patients do not respond to these treatments. Therefore, alternative targets for future therapies are warranted. The current narrative review provides a comprehensive overview of the pathophysiological role of these possible non-CGRP targets in migraine. Findings: We covered targets of the metabotropic receptors (pituitary adenylate cyclase-activating polypeptide (PACAP), vasoactive intestinal peptide (VIP), amylin, and adrenomedullin), intracellular targets (nitric oxide (NO), phosphodiesterase-3 (PDE3) and -5 (PDE5)), and ion channels (potassium, calcium, transient receptor potential (TRP), and acid-sensing ion channels (ASIC)). The majority of non-CGRP targets were able to induce migraine-like attacks, except for (i) calcium channels, as it is not yet possible to directly target channels to elucidate their precise involvement in migraine; (ii) TRP channels, activation of which can induce non-migraine headache; and (iii) ASICs, as their potential in inducing migraine attacks has not been investigated thus far. Drugs that target its receptors exist for PACAP, NO, and the potassium, TRP, and ASIC channels. No selective drugs exist for the other targets, however, some existing (migraine) treatments appear to indirectly antagonize responses to amylin, adrenomedullin, and calcium channels. Drugs against PACAP, NO, potassium channels, TRP channels, and only a PAC1 antibody have been tested for migraine treatment, albeit with ambiguous results. Conclusion: While current research on these non-CGRP drug targets has not yet led to the development of efficacious therapies, human provocation studies using these targets have provided valuable insight into underlying mechanisms of migraine headaches and auras. Further studies are needed on these alternative therapies in non-responders of CGRP(-receptor) targeted therapies with the ultimate aim to pave the way towards a headache-free future for all migraine patients. © 2023, The Author(s).
Other Related Docs
12. The Sense of Stopping Migraine Prophylaxis, Journal of Headache and Pain (2023)
13. Genetics of Migraine: Where Are We Now?, Journal of Headache and Pain (2023)