telcagepant and Neurogenic-Inflammation

Calcitonin gene related peptide (CGRP) has been proposed to contribute to pain transmission and inflammation and for these reasons to the mechanism of migraine. CGRP is, in fact, expressed in and released from a subset of polymodal primary sensory neurons of the trigeminal ganglion. Release of CGRP in the dorsal spinal cord has been associated to nociceptive transmission, and release from perivascular nerve endings causes neurogenic vasodilatation. CGRP levels increase in the cranial circulation during migraine attacks, and GRP injection in migraineurs results in migraine-like attacks. Most importantly, two chemically unrelated CGRP-receptor antagonists, the parenteral agent, olcegepant, and the orally available telcagepant demonstrated efficacy in the treatment of migraine attacks, thus supporting CGRP as an important mediator in migraine.

Topics: Animals; Azepines; Calcitonin Gene-Related Peptide; Calcitonin Gene-Related Peptide Receptor Antagonists; Dipeptides; Humans; Imidazoles; Migraine Disorders; Neurogenic Inflammation; Piperazines; Quinazolines; Receptors, Calcitonin Gene-Related Peptide