• Deirdre M Boucherie, Ruben Dammers, Arnaud Vincent, DanserA H JanAHJDivision of Pharmacology and Vascular Medicine, Department of Internal Medicine, Erasmus MC University Medical Center, Rotterdam, the Netherlands., and Antoinette MaassenVanDenBrink.
• Division of Pharmacology and Vascular Medicine, Department of Internal Medicine, Erasmus MC University Medical Center, Rotterdam, the Netherlands.
• J Headache Pain. 2024 Aug 28; 25 (1): 141141.

BackgroundOrally administered second-generation gepants are effective for the treatment of migraine. The intranasal administration of the third-generation gepant zavegepant might have additional benefits including a rapid onset of action, but it is not clear yet to which extent this has clinical relevance.MethodsWe examined the effect of zavegepant on the relaxations induced by calcitonin gene-related peptide (CGRP) in human isolated middle meningeal arteries. Furthermore, we connected the pharmacodynamics and pharmacokinetics of gepants by combining data from clinical and basic research.ResultsWe showed that 10 nM zavegepant potently antagonized the functional response to CGRP. We also showed that all gepants are effective at inhibiting functional responses to CGRP at their therapeutic plasma concentrations.ConclusionsThe relatively low predicted potency of zavegepant to inhibit CGRP-induced relaxation at therapeutic systemic plasma concentrations may point to the relevance of local delivery to the trigeminovascular system through intranasal administration. This approach may have additional benefits for various groups of patients, including overweight patients.© 2024. The Author(s).

31 keywords...

hide…