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]
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]
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]
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]