Calcitonin gene-related peptide receptor antagonist

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Calcitonin gene-related peptide (CGRP) receptor antagonists, commonly known as gepants, are a class of drugs that act as antagonists of the calcitonin gene-related peptide receptor (CGRPR). [1]

Contents

Several monoclonal antibodies that bind to the CGRP receptor or peptide have been approved for prevention of migraine. [2] Nerve activation triggers the release of CGRP and other neuropeptides, leading to inflammation, pain, and swelling. Three small molecule CGRPR antagonists are approved in the U.S. as antimigraine agents. [3] [4] [5] Drugs of this class have also been investigated for use in osteoarthritis. [6]

Examples

Non-peptide small molecules

Monoclonal antibodies targeting the CGRP receptor

Monoclonal antibodies targeting the CGRP molecule

Necrotizing fasciitis

A study has found botox effective against necrotizing fasciitis caused by S. pyogenes in mice. [20] Its mechanism of action is by blocking CGRP receptor of nerve cells, which trigger intense pain and activate CGRP cascade, which prevents the immune system attacks to control the pathogen. [21] Botox blocks the CGRP cascade of nerve cells. [22]

Migraine

As of 2018, erenumab, brand name Aimovig, was approved in the U.S. for use for migraines. It interacts by blocking the CGRP receptor. [23] As of 2018, fremanezumab, brand name Ajovy, was approved in the U.S. for use for migraines. It interacts with the CGRP protein expressed during an attack. [24] The third approved treatment, as of 2018, galcanezumab, brand name Emgality, was approved in the U.S. for use in migraines. It also interacts with the protein. [25]

As of February 2020, eptinezumab (Vyepti) was approved by the FDA for the treatment of migraine via intravenous infusion as well. [26]

Three small-molecule antagonists have been approved for treatment of migraine: ubrogepant, rimegepant, and atogepant. [4] [3] [5] Ubrogepant and rimegepant are approved for acute treatment. [4] [3] Atogepant and rimegepant are approved for preventative treatment. [5] [3]

References

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  2. "Erenumab (AIMOVIG) Prescribing Information" (PDF). FDA.gov. U.S. Food and Drug Administration. 2018. Archived (PDF) from the original on 2018-12-07.
  3. 1 2 3 4 5 "Nurtec ODT Prescribing Information" (PDF). FDA.gov. U.S. Food and Drug Administration. June 2021. Archived (PDF) from the original on 2021-05-28.
  4. 1 2 3 4 "Ubrogepant Prescribing Information" (PDF). FDA.gov. U.S. Food and Drug Administration. 2019. Archived (PDF) from the original on 2020-07-17.
  5. 1 2 3 4 "Qulipta Prescribing Information" (PDF). FDA.gov. U.S. Food and Drug Administration. March 2022. Archived (PDF) from the original on 2021-11-14.
  6. Nakasa, T; Ishikawa, M; Takada, T; Miyaki, S; Ochi, M (2015). "Attenuation of cartilage degeneration by calcitonin gene-related paptide receptor antagonist via inhibition of subchondral bone sclerosis in osteoarthritis mice". Journal of Orthopaedic Research. 34 (7): 1177–84. doi: 10.1002/jor.23132 . PMID   26686833.
  7. Tfelt-Hansen, P; Olesen, J (April 2011). "Possible Site of Action of CGRP Antagonists in Migraine". Cephalalgia: An International Journal of Headache. 31 (6): 748–50. doi: 10.1177/0333102411398403 . PMID   21383046.
  8. Marcus, R; Goadsby, PJ; Dodick, D; Stock, D; Manos, G; Fischer, TZ (February 2014). "BMS-927711 for the Acute Treatment of Migraine: a Double-Blind, Randomized, Placebo Controlled, Dose-Ranging Trial". Cephalalgia: An International Journal of Headache. 34 (2): 114–25. doi: 10.1177/0333102413500727 . PMID   23965396.
  9. "Zavzpret (zavegepant) nasal spray" (PDF). Food and Drug Administration . 9 March 2023. Retrieved 11 December 2024.
  10. "Pfizer's ZAVZPRET™ (Zavegepant) Migraine Nasal Spray Receives FDA Approval" (Press release). 10 March 2023.
  11. "Press release: Merck Announces Second Quarter 2011 Financial Results". Merck. July 29, 2011. Archived from the original on April 12, 2013.
  12. Recober, A; Russo, AF (August 2007). "Olcegepant, a Non-Peptide CGRP1 Antagonist for Migraine Treatment". IDrugs: The Investigational Drugs Journal. 10 (8): 566–74. PMID   17665333.
  13. Diener, HC; Barbanti, P; Dahlöf, C; Reuter, U; Habeck, J; Podhorna, J (April 2011). "BI 44370 TA, an Oral CGRP Antagonist for the Treatment of Acute Migraine Attacks: Results From a Phase II Study". Cephalalgia: An International Journal of Headache. 31 (5): 573–84. doi: 10.1177/0333102410388435 . PMID   21172952.
  14. Li, CC; Vermeersch, S; Denney, WS; Kennedy, WP; Palcza, J; Gipson, A; Han, TH; Blanchard, R; De Lepeleire, I; Depré, M; Murphy, MG; Van Dyck, K; de Hoon, JN (May 2015). "Characterizing the PK/PD Relationship for Inhibition of Capsaicin-Induced Dermal Vasodilatation by MK-3207, an Oral Calcitonin Gene Related Peptide Receptor Antagonist". British Journal of Clinical Pharmacology. 79 (5): 831–7. doi:10.1111/bcp.12547. PMC   4415719 . PMID   25377933.
  15. Mitsikostas, DD; Reuter, U (2017). "Calcitonin gene-related peptide monoclonal antibodies for migraine prevention: comparisons across randomized controlled studies". Curr Opin Neurol. 30 (3): 272–280. doi:10.1097/WCO.0000000000000438. PMID   28240610. S2CID   46105364.
  16. "Eptinezumab Prescribing Information" (PDF). FDA.gov. U.S. Food and Drug Administration. 2020. Archived (PDF) from the original on 2020-02-25.
  17. H. Spreitzer (29 February 2016). "Neue Wirkstoffe – TEV-48125". Österreichische Apothekerzeitung (in German) (5/2016): 12.
  18. Walter, S; Bigal, ME (March 2015). "TEV-48125: a Review of a Monoclonal CGRP Antibody in Development for the Preventive Treatment of Migraine". Current Pain and Headache Reports. 19 (3): 6. doi:10.1007/s11916-015-0476-1. PMID   25754596. S2CID   8550606.
  19. "Drug Approval Package: Emgality (galcanezumab-gnlm)". www.accessdata.fda.gov. Retrieved 2021-07-09.
  20. Pinho-Ribeiro, Felipe A.; Baddal, Buket; Haarsma, Rianne; O’Seaghdha, Maghnus; Yang, Nicole J.; Blake, Kimbria J.; Portley, Makayla; Verri, Waldiceu A.; Dale, James B.; Wessels, Michael R.; Chiu, Isaac M. (2018-05-17). "Blocking neuronal signaling to immune cells treats streptococcal invasive infection". Cell. 173 (5): 1083–1097.e22. doi:10.1016/j.cell.2018.04.006. ISSN   0092-8674. PMC   5959783 . PMID   29754819.
  21. "How the germ behind flesh-eating disease hijacks neurons to avoid immune destruction".
  22. "Combining Botox and a CGRP antibody: should it be covered by insurance companies? - Migraine Canada™". 2020-05-10. Retrieved 2024-07-30.
  23. Rosenberg, J. (18 May 2018). "FDA Approves Erenumab, First CGRP Inhibitor for Prevention of Migraine". AJMC. Retrieved 6 April 2019.
  24. "FDA Approves Second Anti-CGRP Treatment for Migraine". American Migraine Foundation. Retrieved 6 April 2019.
  25. "Lilly's Emgality (galcanezumab-gnlm) Receives U.S. FDA Approval for the Preventive Treatment of Migraine in Adults". Eli Lilly and Company. Retrieved 6 April 2019.
  26. "Eptinezumab-jjmr (Vyepti) Approved By FDA for Migraine Prevention". American Headache Society. Archived from the original on 2021-10-19. Retrieved 2021-07-09.