Here's an explanation of CGRP and CGRP inhibitors from the study authors:
"Calcitonin gene-related peptide (CGRP) is a neuropeptide thought to have a key role in the pathophysiology of migraine. CGRP concentrations in the cranial circulation may be increased during a migraine attack and CGRP given intravenously triggers a migraine-like headache in people who have migraines. CGRP receptors are found throughout the trigeminal pathways involved in migraine headache pain and have been localised to primary sensory neurons in the trigeminal ganglion, central second-order pain-relay neurons in the trigeminal nucleus caudalis, and smooth muscle cells of the meningeal vasculature. Antagonism of these receptors has thus become an important target for new migraine treatments. Since antagonists of CGRP receptor do not seem to have direct vasoconstrictor properties, they might be free of the cardiovascular concerns associated with triptans."1
The authors also noted a very important issue:
"One potential benefit of the new CGRP receptor antagonist class of acute migraine treatments is the absence of vasoconstriction, a liability of the triptans, which may allow for the safe administration of telcagepant in patients with migraine with cardiovascular disease. However, such patients were excluded from the present study because of the contraindication for zolmitriptan, and further studies are necessary to determine the safety of telcagepant in patients with cardiovascular disease. Additional studies are also necessary to assess the long-term efficacy and safety profile of telcagepant in patients treating more than one migraine attack."1
Summary and comments:
For many Migraineurs, the triptans have been "miracle drugs." Still, due to their vasoconstrictive action, triptans are not a good choice for many Migraineurs. The development of telcagepant marks the introduction of the first new type of acute Migraine medication since the introduction of Imitrex in 1992. Future studies will determine if telcagepant is safe for patients with cardiovascular disease, uncontrolled hypertension, and history of stroke.
