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Targeting CGRP and 5-HT1F Receptors for the Acute Therapy of Migraine: A Literature Review.
Headache. 2019 07; 59 Suppl 2:3-19.H

Abstract

OBJECTIVE

To review and highlight current literature on emerging acute migraine treatments, focusing on CGRP receptor antagonists, gepants, and 5-HT1F receptor agonists (ditans).

BACKGROUND

Current acute migraine therapy consists of nonspecific analgesia and triptans. Limitations to these medicines, including lack of efficacy in many patients, side effects and the contraindication of triptans in patients with cardiovascular disease, suggest that there is an unmet need for new treatments. Studies of serotonin pharmacology led to the development of triptans, 5-HT1B/1D receptor agonists, some of which have actions at the 5-HT1F receptor. Exploration of the role of calcitonin gene-related peptide (CGRP) has resulted in the development of CGRP receptor antagonists.

METHOD

The authors performed a literature search of Pubmed and Cochrane databases as well as reviewed abstracts presented at meetings: American Headache Society, American Academy of Neurology, European Headache Federation and the Migraine Trust International Symposium, as well as on-line sources. The authors briefly detail the relevant migraine pathophysiology pertaining to 5-HT1F receptor and the CGRP pathway relevant to acute therapies. Recent clinical trials of acute therapies in which 5-HT1F receptor agonists or CGRP receptor antagonists were studied are summarized.

RESULTS

Two 5-HT1F receptor agonists have reached phase II clinical trials. One, lasmiditan, has completed 2 phase III clinical trials, demonstrating a significant effect for pain freedom and most bothersome symptom at 2 hours. Among the 6 gepants tested for the acute treatment of migraine to date, after issues for some of hepatic safety or efficacy, 2 CGRP receptor antagonists, rimegepant and ubrogepant, have completed phase III trials showing efficacy and safety.

CONCLUSION

Current available therapies have either been nonspecific or had important limitations, including in patients with cardiovascular risk factors. Phase III clinical trials of lasmiditan, rimegepant and ubrogepant all met their primary endpoints, so the options for migraine-targeted acute therapy will likely soon increase.

Links

Publisher Full Text (DOI)

Authors+Show Affiliations

Moreno-Ajona D
Basic and Clinical Neurosciences, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK. NIHR-Wellcome Trust King's Clinical Research Facility/SLaM Biomedical Research Centre, King's College Hospital, London, UK.
Chan C
Basic and Clinical Neurosciences, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK. NIHR-Wellcome Trust King's Clinical Research Facility/SLaM Biomedical Research Centre, King's College Hospital, London, UK.
Villar-Martínez MD
Basic and Clinical Neurosciences, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK. NIHR-Wellcome Trust King's Clinical Research Facility/SLaM Biomedical Research Centre, King's College Hospital, London, UK.
Goadsby PJ
Basic and Clinical Neurosciences, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK. NIHR-Wellcome Trust King's Clinical Research Facility/SLaM Biomedical Research Centre, King's College Hospital, London, UK.

MeSH

Calcitonin Gene-Related Peptide Receptor AntagonistsHumansMigraine DisordersSerotonin 5-HT1 Receptor Agonists

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

31291016

Citation

Moreno-Ajona, David, et al. "Targeting CGRP and 5-HT1F Receptors for the Acute Therapy of Migraine: a Literature Review." Headache, vol. 59 Suppl 2, 2019, pp. 3-19.
Moreno-Ajona D, Chan C, Villar-Martínez MD, et al. Targeting CGRP and 5-HT1F Receptors for the Acute Therapy of Migraine: A Literature Review. Headache. 2019;59 Suppl 2:3-19.
Moreno-Ajona, D., Chan, C., Villar-Martínez, M. D., & Goadsby, P. J. (2019). Targeting CGRP and 5-HT1F Receptors for the Acute Therapy of Migraine: A Literature Review. Headache, 59 Suppl 2, 3-19. https://doi.org/10.1111/head.13582
Moreno-Ajona D, et al. Targeting CGRP and 5-HT1F Receptors for the Acute Therapy of Migraine: a Literature Review. Headache. 2019;59 Suppl 2:3-19. PubMed PMID: 31291016.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Targeting CGRP and 5-HT1F Receptors for the Acute Therapy of Migraine: A Literature Review. AU - Moreno-Ajona,David, AU - Chan,Calvin, AU - Villar-Martínez,María Dolores, AU - Goadsby,Peter J, PY - 2019/06/07/accepted PY - 2019/7/11/entrez PY - 2019/7/11/pubmed PY - 2020/7/21/medline KW - 5-HT1F KW - acute medications KW - acute therapy KW - calcitonin gene-related peptide KW - migraine SP - 3 EP - 19 JF - Headache JO - Headache VL - 59 Suppl 2 N2 - OBJECTIVE: To review and highlight current literature on emerging acute migraine treatments, focusing on CGRP receptor antagonists, gepants, and 5-HT1F receptor agonists (ditans). BACKGROUND: Current acute migraine therapy consists of nonspecific analgesia and triptans. Limitations to these medicines, including lack of efficacy in many patients, side effects and the contraindication of triptans in patients with cardiovascular disease, suggest that there is an unmet need for new treatments. Studies of serotonin pharmacology led to the development of triptans, 5-HT1B/1D receptor agonists, some of which have actions at the 5-HT1F receptor. Exploration of the role of calcitonin gene-related peptide (CGRP) has resulted in the development of CGRP receptor antagonists. METHOD: The authors performed a literature search of Pubmed and Cochrane databases as well as reviewed abstracts presented at meetings: American Headache Society, American Academy of Neurology, European Headache Federation and the Migraine Trust International Symposium, as well as on-line sources. The authors briefly detail the relevant migraine pathophysiology pertaining to 5-HT1F receptor and the CGRP pathway relevant to acute therapies. Recent clinical trials of acute therapies in which 5-HT1F receptor agonists or CGRP receptor antagonists were studied are summarized. RESULTS: Two 5-HT1F receptor agonists have reached phase II clinical trials. One, lasmiditan, has completed 2 phase III clinical trials, demonstrating a significant effect for pain freedom and most bothersome symptom at 2 hours. Among the 6 gepants tested for the acute treatment of migraine to date, after issues for some of hepatic safety or efficacy, 2 CGRP receptor antagonists, rimegepant and ubrogepant, have completed phase III trials showing efficacy and safety. CONCLUSION: Current available therapies have either been nonspecific or had important limitations, including in patients with cardiovascular risk factors. Phase III clinical trials of lasmiditan, rimegepant and ubrogepant all met their primary endpoints, so the options for migraine-targeted acute therapy will likely soon increase. SN - 1526-4610 UR - https://www.unboundmedicine.com/medline/citation/31291016/Targeting_CGRP_and_5_HT1F_Receptors_for_the_Acute_Therapy_of_Migraine:_A_Literature_Review_ DB - PRIME DP - Unbound Medicine ER -