Calcitonin gene-related peptide receptor antagonist
Class of drugs
From Wikipedia, the free encyclopedia
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]
The CGRP family of small proteins are present in the sensory nerves of the head and neck and are involved in transmission of pain.[2] Nerve activation can trigger the release of CGRP and other neuropeptides, leading to inflammation, pain, and swelling in the case of migraine.[3] Several monoclonal antibodies that bind to the CGRP receptor or peptide have been approved for prevention of migraine.[4] As of March 11, 2024, the American Headache Society issued a statement that "CGRP targeting therapies are a first-line option for migraine prevention"[2] in the United States. The prior use of non-specific migraine preventive medication approaches is therefore no longer required before CGRP treatments can be prescribed.[2] Small molecule CGRPR antagonists have also been approved in the U.S. as antimigraine agents.[5][6][7]
Drugs of this class have also been investigated for use in osteoarthritis.[8]
Examples of CGRP inhibitors
Small molecule CGRP antagonists are generally administered by mouth as pills. One type is a nasal spray. In contrast, CGRP monoclonal antibodies involve large molecules which must be given intravenously or as injections. Injections can be self-administered with an automatic pen monthly or quarterly, depending on the drug.[9]
Small molecule CGRP antagonists (gepants)
- Ubrogepant is approved for acute treatment of migraines[10][6][2]
- Rimegepant (BMS-927711) is approved for acute migraine treatment (since February 2020)[11] and for preventive treatment of episodic migraines (since May 2021).[12][5][2]
- Atogepant (AGN-241689) is approved for preventative treatment of migraines[7][2]
- Zavegepant (BHV- 3500) is a nasal spray approved for acute treatment of migraines.[13][14][2]
- Telcagepant (MK-0974), reached phase III clinical trials; development discontinued in 2011.[15]
- Olcegepant (BIBN-4096BS) is a drug candidate[16]
- BI 44370 TA (BI 44370)[17]
- MK-3207[18]
- SB-268262
Monoclonal antibodies targeting the CGRP receptor
Monoclonal antibodies targeting the CGRP molecule
- Eptinezumab (ALD403) is approved for prevention of migraine.[20][2]
- Fremanezumab (TEV-48125) is approved for prevention of migraine.[21][22][2]
- Galcanezumab (LY2951742) is approved for prevention of migraine and cluster headaches.[23][2]
Medical applications
Migraine
As of 2024, eight blockers of CGRP or its receptor have been approved by the US Food and Drug Administration for the treatment or prevention of migraine.[24] These include erenumab, brand name Aimovig, approved in the U.S. for use for migraines in 2018. It interacts by blocking the CGRP receptor.[25] 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.[26] Galcanezumab, brand name Emgality, was the third treatment to be approved in the U.S. in 2018 for use in migraines. It also interacts with the CGRP protein.[27]
As of February 2020, eptinezumab (Vyepti) was approved by the FDA for the treatment of migraine via intravenous infusion as well.[28]
Three small-molecule antagonists have been approved for treatment of migraine: ubrogepant, rimegepant, and atogepant.[6][5][7] Ubrogepant and rimegepant are approved for acute treatment.[6][5] Atogepant and rimegepant are approved for preventative treatment.[7][5]
Necrotizing fasciitis
A study has found botox effective against necrotizing fasciitis caused by S. pyogenes in mice.[29] 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.[30] Botox blocks the CGRP cascade of nerve cells.[31]