The 5-HT1F receptor as the target of ditans in migraine - from bench to bedside

doi:10.1038/s41582-023-00842-x

Review

. 2023 Aug;19(8):489-505.

doi: 10.1038/s41582-023-00842-x. Epub 2023 Jul 12.

The 5-HT_1F receptor as the target of ditans in migraine - from bench to bedside

Dimos D Mitsikostas¹, Christian Waeber^{2

3}, Margarita Sanchez-Del-Rio⁴, Bianca Raffaelli^{5

6}, Håkan Ashina^{6

7

8}, Antoinette Maassen van den Brink⁹, Anna Andreou^{10

11}, Patricia Pozo-Rosich^{12

13

14}, Alan Rapoport¹⁵, Messoud Ashina⁶, Michael A Moskowitz¹⁶

Affiliations

¹ 1st Neurology Department, Eginition Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece. dmitsikostas@uoa.gr.
² School of Pharmacy, University College Cork, Cork, Ireland.
³ Department of Pharmacology and Therapeutics, University College Cork, Cork, Ireland.
⁴ Neurology Department, Clinica Universidad de Navarra, Madrid, Spain.
⁵ Department of Neurology, Charité Universitätsmedizin Berlin, Berlin, Germany.
⁶ Department of Neurology, Danish Headache Center, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
⁷ Department of Brain and Spinal Cord Injury, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
⁸ Department of Anaesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
⁹ Division of Vascular Medicine and Pharmacology, Department of Internal Medicine, Erasmus MC University Medical Center, Rotterdam, Netherlands.
¹⁰ Wolfson Centre for Age-Related Diseases, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
¹¹ Headache Centre, Guy's and St Thomas's NHS Foundation Trust, King's Health Partners, London, UK.
¹² Neurology Department, Vall d'Hebron University Hospital, Barcelona, Spain.
¹³ Headache Unit, Neurology Department, Vall d'Hebron University Hospital, Barcelona, Spain.
¹⁴ Headache and Neurological Pain Research Group, Vall d'Hebron Research Institute, Department of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain.
¹⁵ Department of Neurology, The David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
¹⁶ Departments of Radiology and Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA.

PMID: 37438431
DOI: 10.1038/s41582-023-00842-x

Review

The 5-HT_1F receptor as the target of ditans in migraine - from bench to bedside

Dimos D Mitsikostas et al. Nat Rev Neurol. 2023 Aug.

. 2023 Aug;19(8):489-505.

doi: 10.1038/s41582-023-00842-x. Epub 2023 Jul 12.

Authors

Affiliations

¹ 1st Neurology Department, Eginition Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece. dmitsikostas@uoa.gr.
² School of Pharmacy, University College Cork, Cork, Ireland.
³ Department of Pharmacology and Therapeutics, University College Cork, Cork, Ireland.
⁴ Neurology Department, Clinica Universidad de Navarra, Madrid, Spain.
⁵ Department of Neurology, Charité Universitätsmedizin Berlin, Berlin, Germany.
⁶ Department of Neurology, Danish Headache Center, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
⁷ Department of Brain and Spinal Cord Injury, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
⁸ Department of Anaesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
⁹ Division of Vascular Medicine and Pharmacology, Department of Internal Medicine, Erasmus MC University Medical Center, Rotterdam, Netherlands.
¹⁰ Wolfson Centre for Age-Related Diseases, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
¹¹ Headache Centre, Guy's and St Thomas's NHS Foundation Trust, King's Health Partners, London, UK.
¹² Neurology Department, Vall d'Hebron University Hospital, Barcelona, Spain.
¹³ Headache Unit, Neurology Department, Vall d'Hebron University Hospital, Barcelona, Spain.
¹⁴ Headache and Neurological Pain Research Group, Vall d'Hebron Research Institute, Department of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain.
¹⁵ Department of Neurology, The David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
¹⁶ Departments of Radiology and Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA.

PMID: 37438431
DOI: 10.1038/s41582-023-00842-x

Abstract

Migraine is a leading cause of disability in more than one billion people worldwide, yet it remains universally underappreciated, even by individuals with the condition. Among other shortcomings, current treatments (often repurposed agents) have limited efficacy and potential adverse effects, leading to low treatment adherence. After the introduction of agents that target the calcitonin gene-related peptide pathway, another new drug class, the ditans - a group of selective serotonin 5-HT_1F receptor agonists - has just reached the international market. Here, we review preclinical studies from the late 1990s and more recent clinical research that contributed to the development of the ditans and led to their approval for acute migraine treatment by the US Food and Drug Administration and the European Medicines Agency.

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References

1. GBD 2016 Headache Collaborators. Global, regional, and national burden of migraine and tension-type headache, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol. 17, 954–976 (2018); erratum 20, e7 (2021). - DOI
1. Headache Classification Committee of the International Headache Society (IHS). The International Classification of Headache Disorders, 3rd edition. Cephalalgia 38, 1–211 (2018). - DOI
1. Mitsikostas, D. D. et al. European Hedache Federation consensus on technical investigation for primary headache disorders. J. Headache Pain. 17, 5 (2015). - PubMed - DOI
1. Ashina, S. et al. Medication overuse headache. Nat. Rev. Dis. Prim. 9, 5 (2023). - PubMed - DOI
1. Diener, H. C. et al. European Academy of Neurology guideline on the management of medication-overuse headache. Eur. J. Neurol. 27, 1102–1116 (2020). - PubMed - DOI

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[1] GBD 2016 Headache Collaborators. Global, regional, and national burden of migraine and tension-type headache, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol. 17, 954–976 (2018); erratum 20, e7 (2021). - DOI

[2] GBD 2016 Headache Collaborators. Global, regional, and national burden of migraine and tension-type headache, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol. 17, 954–976 (2018); erratum 20, e7 (2021). - DOI

[3] Headache Classification Committee of the International Headache Society (IHS). The International Classification of Headache Disorders, 3rd edition. Cephalalgia 38, 1–211 (2018). - DOI

[4] Headache Classification Committee of the International Headache Society (IHS). The International Classification of Headache Disorders, 3rd edition. Cephalalgia 38, 1–211 (2018). - DOI

[5] Mitsikostas, D. D. et al. European Hedache Federation consensus on technical investigation for primary headache disorders. J. Headache Pain. 17, 5 (2015). - PubMed - DOI

[6] Mitsikostas, D. D. et al. European Hedache Federation consensus on technical investigation for primary headache disorders. J. Headache Pain. 17, 5 (2015). - PubMed - DOI

[7] Ashina, S. et al. Medication overuse headache. Nat. Rev. Dis. Prim. 9, 5 (2023). - PubMed - DOI

[8] Ashina, S. et al. Medication overuse headache. Nat. Rev. Dis. Prim. 9, 5 (2023). - PubMed - DOI

[9] Diener, H. C. et al. European Academy of Neurology guideline on the management of medication-overuse headache. Eur. J. Neurol. 27, 1102–1116 (2020). - PubMed - DOI

[10] Diener, H. C. et al. European Academy of Neurology guideline on the management of medication-overuse headache. Eur. J. Neurol. 27, 1102–1116 (2020). - PubMed - DOI

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The 5-HT_1F receptor as the target of ditans in migraine - from bench to bedside

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The 5-HT_1F receptor as the target of ditans in migraine - from bench to bedside

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