Nurtec (Rimegepant) Mechanism of Action
Rimegepant is a calcitonin gene-related peptide (CGRP) receptor antagonist that blocks the CGRP receptor-binding site, thereby preventing CGRP from binding to its receptor and interrupting the trigeminal nerve pain and inflammation pathway central to migraine pathophysiology. 1, 2
How CGRP Antagonism Works
CGRP is a protein that contributes to trigeminal nerve pain and inflammation, playing a critical role in migraine pathophysiology. 1
Rimegepant specifically blocks the CGRP receptor-binding site, preventing the peptide from activating the receptor. 1
This mechanism differs from CGRP monoclonal antibodies (like galcanezumab, fremanezumab, and eptinezumab), which block the peptide itself from binding to the receptor, or erenumab, which blocks the receptor-binding site through a different molecular approach. 1
Rimegepant belongs to the "gepant" class of medications, which are small-molecule CGRP receptor antagonists. 1, 3
Pharmacodynamic Effects
The exact relationship between rimegepant's pharmacodynamic activity and the mechanism by which it exerts clinical effects remains unknown. 2
Rimegepant does not cause clinically relevant changes in resting blood pressure, even when co-administered with sumatriptan, and does not prolong the QT interval at doses up to 4 times the recommended dose. 2
The drug is primarily metabolized by CYP3A4 and to a lesser extent by CYP2C9, with an elimination half-life of approximately 11 hours. 2
Clinical Distinction from Other Migraine Medications
Unlike triptans, which bind to 5-HT1B and 5-HT1D serotonin receptors, rimegepant works exclusively through CGRP receptor antagonism. 1
Unlike ditans (such as lasmiditan), which block CGRP release by binding to 5-HT1F receptors, rimegepant directly blocks the CGRP receptor after the peptide has already been released. 1
Rimegepant is available as an orally disintegrating tablet (ODT), offering convenience and potentially faster response time compared to conventional tablet formulations. 3