Small molecule CGRP receptor antagonists for the preventive treatment of migraine: A review

To review the chemistry, pharmacodynamics, pharmacokinetics, efficacy, safety, and tolerability profile of small molecule CGRP receptor antagonists for the preventive treatment of migraine. We conducted a review of atogepant, rimegepant, and zavegepant for the preventive treatment of migraine. The search was carried out in Medline via PubMed, Embase, and Clinical trials, up to January 2022. Five hundred ninety-nine studies were found, of which 113 were in Medline via PubMed and 486 in Embase. The review included ten studies. Moreover, 16 clinical trials evaluated atogepant, rimegepant, and zavegepant. Atogepant and rimegepant reduced the number of migraine days per month and improved the Migraine-Specific Quality of Life Questionnaire role function (restrictive domain score). The frequency of adverse events and the treatment discontinuation were similar between the small molecule CGRP receptor antagonists and placebo. Zavegepant is currently being evaluated in a phase-2/3 clinical trial for migraine prevention, with no available findings. Atogepant and rimegepant were effective and safe for the preventive treatment of migraine in adults. Long-term safety studies and comparisons of atogepant and rimegepant with other established treatments for migraine prevention are required. [Display omitted] •Atogepant and rimegepant were approved for the preventive treatment of migraine by FDA in 2021.•These drugs presented better efficacy and similar safety than placebo.•Zavegepant is currently being evaluated in a phase-2/3 clinical trial for migraine prevention, with no available findings.