Calcitonin gene-related peptide receptor antagonists for migraine.
BACKGROUND
Migraine is a highly prevalent disabling condition, and the current treatment options are not satisfactory. The role of calcitonin gene-related peptide (CGRP) in migraine pathophysiology is well established. CGRP receptor antagonists address this new target and have the potential to improve therapy for both responders and non-responders to previous options.


METHODS
This review describes CGRP, its receptors and their role in the pathophysiology of migraine. CGRP receptor antagonists are a recent development; all reported antagonists are reported in chronological order. The experimental evidence, as well as all clinical trials since the first proof-of-concept study in 2004, is discussed.


RESULTS
An overview of the CGRP system and why it provides an attractive drug target for headache. The main focus is on the currently presented CGRP receptor antagonists and clinical evidence for this new therapeutic option.


CONCLUSIONS
CGRP receptor antagonists will provide an additional and valuable therapeutic option for the treatment of headaches.
Fischer
Michael J M
MJ
Department of Pharmacology, University of Cambridge, Cambridge, UK. mjmf2@cam.ac.uk
D000818:Animals; D001381:Azepines / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D002986:Clinical Trials as Topic; D004151:Dipeptides / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D007093:Imidazoles / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D007191:Indazoles / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D008881:Migraine Disorders / Q000188:drug therapy* / Q000378:metabolism; D010879:Piperazines; D011799:Quinazolines / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D052999:Quinazolinones / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D016896:Treatment Outcome; D014276:Trigeminal Nerve / Q000378:metabolism
C531228:4-(8-fluoro-2-oxo-1,2-dihydroquinazolin-3(4H)-yl)-N-(3-(7-methyl-1H-indazol-5-yl)-1-oxo-1-(4-(piperidin-1-yl)piperidin-1-yl)propan-2-yl)piperidine-1-carboxamide; D001381:Azepines; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D004151:Dipeptides; D007093:Imidazoles; D007191:Indazoles; D010879:Piperazines; D011799:Quinazolines; D052999:Quinazolinones; C525458:telcagepant; D015740:Calcitonin Gene-Related Peptide; C406305:olcegepant