Abstract
Cerebral blood vessels are innervated by sensory nerves that store several neurotransmitters. In primary headaches, there is a clear association between head pain and the release of the neuropeptide calcitonin gene-related peptide (CGRP). Furthermore, when triptan antimigraine agents are administered, headache subsides and the neuropeptide release normalises, in part via a presynaptic effect.
The central role of CGRP in primary headaches has led to the search for suitable antagonists of the receptors for this neuropeptide, which it is hoped will have less cardiovascular adverse effects than the triptans. Recently, the initial pharmacological profile of such a group of compounds has been disclosed. These compounds are small molecules with high selectivity for human CGRP receptors. Hypothetically, these agents will be efficacious in the relief of migraine headaches via blockade of the effects of CGRP.
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Notes
pA2 is the negative logarithm of the drug concentration causing a two-fold shift to the right of a dose-response curve.
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Acknowledgements
The studies of the authors’ reviewed have been supported by the Swedish Research Council (project no. 5958).
Dr Edvinsson has no potential conflicts of interest that are directly relevant to the contents of this article.
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Edvinsson, L. Calcitonin Gene-Related Peptide (CGRP) and the Pathophysiology of Headache. Mol Diag Ther 15, 745–753 (2001). https://doi.org/10.2165/00023210-200115100-00001
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DOI: https://doi.org/10.2165/00023210-200115100-00001