Calcitonin gene-related peptide receptor antagonist

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]

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

• 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

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

Monoclonal antibodies targeting the CGRP molecule

• Eptinezumab (ALD403) is approved for prevention of migraine.^[16]
• Fremanezumab (TEV-48125) is approved for prevention of migraine.^[17][18]
• Galcanezumab (LY2951742) is approved for prevention of migraine and cluster headaches.^[19]

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]