Plasma Adrenomedullin Levels In Patients With Migraine During Naturel Attack And Attack Free Period

Akcali, Aylin; Geyik, Sırma; Dogru, Ilker; Doğru, Arzu; Yürekli, Muhittin; Neyal, Abdurrahman; Balat, Ayşe; Neyal, Münife

doi:10.17546/msd.08866

Cited by 1 publication

(1 citation statement)

References 26 publications

(30 reference statements)

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“…Hence, adrenomedullin might induce migraine at possibly supraphysiological concentrations, by also activating the CGRP receptor, but the possibility of the occurrence of an attack at physiological concentrations is unclear to the best of our knowledge. A previous study in migraine patients showed lower plasma levels of adrenomedullin in the ictal and interictal phase compared to controls, suggesting an imbalance between CGRP and adrenomedullin in the migraine pathophysiology [ 101 ]. Moreover, which adrenomedullin-responsive receptors (AM 1 , AM 2 ) or the CGRP receptor mediate these migraine-like responses have yet to be elucidated [ 99 ].…”

Section: Metabotropic Receptors (G Protein-coupled Receptors)mentioning

confidence: 99%

Future targets for migraine treatment beyond CGRP

Al-Hassany¹,

Boucherie²,

Creeney³

et al. 2023

J Headache Pain

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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.

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Section: Metabotropic Receptors (G Protein-coupled Receptors)mentioning

confidence: 99%