Mass spectrometry mapping reveals atogepant and rimegepant distribute to the dura, trigeminal ganglion, brain cortex, and hypothalamus in mice.
5 tissuesDrug levels measured in plasma, dura, trigeminal ganglion, cortex, and hypothalamus
What the researchers found
Both atogepant and rimegepant distribute to central migraine-relevant structures including the trigeminal ganglion, brain cortex, and hypothalamus.
Why it matters
Understanding where gepants act is crucial for optimizing migraine treatment and developing next-generation CGRP-targeted drugs.
The numbers in context
Measured in plasma, dura mater, trigeminal ganglion, parietal cortex, and hypothalamus. Compared to oxazepam (brain-permeant reference). Interspecies dose conversion. Single and repeated dosing.
How the study worked
Mass spectrometry biodistribution analysis of atogepant and rimegepant in mouse peripheral and central nervous system structures.
Who was studied
Mice
What this study cannot tell us
Mouse biodistribution may not directly translate to human pharmacokinetics. Mass spectrometry measures total drug, not receptor-bound fraction.
How to read the evidence
Preclinical pharmacokinetic study with quantitative mass spectrometry — robust methodology for biodistribution questions.
When this study was published
Published in 2025, informing the ongoing debate about gepant mechanisms of action.
The bigger picture
This challenges the dogma that gepants work only peripherally, suggesting they may have direct central nervous system effects that contribute to their efficacy.
Questions still open
- Do the central concentrations of gepants reach therapeutically relevant levels?
- Does central penetration contribute to side effects as well as efficacy?
Common questions
Do gepant migraine drugs work in the brain?
What is the difference between atogepant and rimegepant?
Read the original research
Biodistribution of atogepant and rimegepant in mouse peripheral and central structures of relevance to migraine pathogenesis.
Cephalalgia : an international journal of headache, 45(11), 3331024251378713
Citation
Pistolesi, Alessandra; De Cesaris, Francesco; Buonvicino, Daniela; Chiarugi, Alberto. (2025). Biodistribution of atogepant and rimegepant in mouse peripheral and central structures of relevance to migraine pathogenesis.. Cephalalgia : an international journal of headache, 45(11), 3331024251378713. https://doi.org/10.1177/03331024251378713