Rimegepant

The theory most widely accepted today says migraine starts with a problem in the central nervous system, in particular the trigeminal ganglion. When the trigeminal ganglion is activated, it stimulates trigeminal afferents. These project to the spinal cord and synapse on several pain-sensing structures inside and outside the skull, such as the dura mater. Second-order ascending neurons then carry the pain signals to the brainstem, hypothalamus and thalamic nuclei, and from there to several cortical regions (for example the auditory, visual and motor cortices). The trigeminal ganglion seems to amplify and prolong the migraine headache pain. It does this by activating perivascular fibers and releasing molecules involved in generating pain, such as calcitonin gene-related peptide (CGRP). The α-isoform of CGRP is expressed in primary sensory neurons and is a potent vasodilator, and it has been linked to migraine pathogenesis. CGRP levels rise sharply during migraine attacks and return to normal after treatment with triptan medications, and intravenous infusions of CGRP have triggered migraine-like headaches in people with migraine. Besides widening blood vessels, CGRP appears to be a pronociceptive factor, meaning it changes how excitable neurons are and so makes pain responses easier. Rimegepant is an antagonist of the calcitonin gene-related peptide receptor. It competes with CGRP for a place on these receptors, which stops CGRP from acting and from amplifying and prolonging the headache pain, and so the headache ends.