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Calcitonin gene-related peptide receptor antagonist

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

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

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Non-peptide small molecules

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  • Ubrogepant is approved for acute treatment of migraines[7][4]
  • Rimegepant (BMS-927711) is approved for acute and preventative treatment of migraines[8][3]
  • Atogepant (AGN-241689) is approved for preventative treatment of migraines[5]
  • Zavegepant (BHV- 3500) is a nasal spray approved for acute treatment of migraines.[9][10]
  • Telcagepant (MK-0974), reached phase III clinical trials; development discontinued in 2011.[11]
  • Olcegepant (BIBN-4096BS) is a drug candidate[12]
  • BI 44370 TA (BI 44370)[13]
  • MK-3207[14]
  • SB-268262

Monoclonal antibodies targeting the CGRP receptor

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  • Erenumab (AMG-334) is approved for prevention of migraine.[15]

Monoclonal antibodies targeting the CGRP molecule

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Necrotizing fasciitis

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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

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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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  1. ^ Rashid, Abin; Manghi, Ali (2024), "Calcitonin Gene-Related Peptide Receptor", StatPearls, Treasure Island (FL): StatPearls Publishing, PMID 32809483, retrieved 2024-07-30
  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. ^ a b c d e "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. ^ a b c d "Ubrogepant Prescribing Information" (PDF). FDA.gov. U.S. Food and Drug Administration. 2019. Archived (PDF) from the original on 2020-07-17.
  5. ^ a b c d "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. ^ https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2023/216386Orig1s000ltr.pdf [bare URL PDF]
  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. Retrieved 2021-07-09.
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