Calcitonin Gene-Related Peptide (CGRP) plays a pivotal role in migraine pathophysiology. Two types of CGRP function-blocking modalities, monoclonal antibodies, and small molecules (gepants), have been developed to target the CGRP ligands and CGRP receptors. Four CGRP monoclonal antibodies have received FDA approval for the prevention of migraine: erenumab, fremanezumab, galcanezumab, and eptinezumab. Two gepants have been approved by the FDA for the acute treatment of migraine: ubrogepant and rimegepant. (Chiang et al, 2020)
First- and second-generation calcitonin gene-related peptide (CGRP) receptor antagonists, namely gepants, is a class of drugs primarily developed for the acute treatment of migraine. Available data suggest that second generation of gepants has clinical efficacy similar to triptans and lasmiditan (5-HT1F receptor agonist) and has improved tolerability. (Negro, 2019)
Given the preventive effect, it seems likely that gepants will not lead to medication overuse headache. They will likely have no cardiovascular warnings. (Moreno-Ajona et al, 2020)
Chiang CC, Schwedt TJ. Calcitonin gene-related peptide (CGRP)-targeted therapies as preventive and acute treatments for migraine-The monoclonal antibodies and gepants. Prog Brain Res. 2020;255:143-170. doi: 10.1016/bs.pbr.2020.06.019. Epub 2020 Jul 22. PMID: 33008505.
Negro A, Martelletti P. Gepants for the treatment of migraine. Expert Opin Investig Drugs. 2019 Jun;28(6):555-567. doi: 10.1080/13543784.2019.1618830. Epub 2019 May 17. PMID: 31081399.
Moreno-Ajona D, Pérez-Rodríguez A, Goadsby PJ. Gepants, calcitonin-gene-related peptide receptor antagonists: what could be their role in migraine treatment? Curr Opin Neurol. 2020 Jun;33(3):309-315. doi: 10.1097/WCO.0000000000000806. PMID: 32251023.