Novel migraine therapy with calcitonin gene-regulated peptide receptor antagonists.
Primary headaches, for example, migraine and cluster headaches represent the most prevalent neurological disorders, affecting up to 15-20% of the adult population. There is a clear association between head pain and the release of calcitonin gene-related peptide (CGRP). In this review the role of CGRP in human cranial circulation is described and the role for specific CGRP antagonism elucidated. It is well known that triptans (5-HT(1B/1D) agonist) alleviate headache in part through normalisation of CGRP levels. The central role of CGRP in migraine pathophysiology has resulted in the development of small-molecule CGRP antagonists with no cardiovascular side effects. Such compounds have high selectivity for human CGRP receptors and are efficacious in the relief of acute migraine attacks. Research indicates that they effect the abluminal side of the blood-brain barrier and that they are not vasoconstrictive, providing a new dimension in therapy.
Edvinsson
Lars
L
Lund University Hospital, Department of Medicine, Institute of Clinical Sciences, S-221 85 Lund, Sweden. lars.edvinsson@med.lu.se
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D006801:Humans; D008881:Migraine Disorders / Q000188:drug therapy* / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000378:metabolism; D018015:Receptors, Calcitonin Gene-Related Peptide / Q000819:agonists / Q000378:metabolism
D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D018377:Neurotransmitter Agents; D018015:Receptors, Calcitonin Gene-Related Peptide; D015740:Calcitonin Gene-Related Peptide