Figure 1
Schematic representation of the probable mechanisms of the action of antimigraine remedies, either currently used, or proven effective in clinical trials (gray boxes) or of novel medicines (empty box), regarding their ability to modulate the release of calcitonin gene related peptide (CGRP) or the activation of its receptor (CGRP-R). (1) Non steroidal antiinflammatory drugs (NSAIDs) block prostaglandin synthesis and the ensuing nociceptor sensitization and CGRP release evoked by prostaglandin receptor (PG-R) activation. (2) Triptans, by activating neuronal 5HT1D receptors, inhibit CGRP release. (3) CGRP-R antagonists inhibit the action of CGRP on effector cells. (4) Antagonists of transient receptor potential channels (TRPs), including TRP ankyrin 1 (TRPA1), block the ability of a series of stimulants (for TRPA1, cigarette smoke, acrolein, nitric oxide, umbellulone, and others) to release CGRP. All medicines may act at both peripheral and central endings of trigeminal nociceptors. Receptor/channel activation may trigger/facilitate (+) or inhibit (−) CGRP release.