[CGRP antagonists: novel concept for treatment of migraine].
Migraine is a complex neurological disorder that affects a significant proportion of the adult population worldwide. It is associated with an increase in plasma calcitonin gene-related peptide (CGRP) level. CGRP, a neuropeptide released from activated trigeminal sensory nerves, dilates intracranial blood vessels and transmits vascular nociception. Therefore, it is proposed that CGRP may have an important role in migraine pathophysiology and inhibition of trigeminal CGRP release or CGRP-induced cranial vasodilatation may abort migraine. The mode of action of CGRP antagonists is inhibition of neurogenic vasodilatation and inflammation, an additional neuronal action cannot be ruled out. Both intravenous applied olcegepant (BIBN 4096) and the oral telcagepant (MK-0974) were tested in clinical trials and showed clinical benefit and excellent tolerability, with recent presentation of phase III data on telcagepant suggesting that proof of concept is positive. CGRP receptor antagonists terminate migraine with efficacy similar to triptans. The results from clinical trials suggest that this new type of drug might offer advantages over existing therapies without vasoconstrictive or vascular side effects.
Nieber
Karen
K
Pharmakologie fOr Naturwissenschaftler, Talstrasse 33, 04103 Leipzig. Nieber@rz.uni-leipzig.de
D001381:Azepines / Q000627:therapeutic use; D015740:Calcitonin Gene-Related Peptide / Q000502:physiology; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D004151:Dipeptides / Q000627:therapeutic use; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use; D008881:Migraine Disorders / Q000188:drug therapy* / Q000503:physiopathology; D011799:Quinazolines / Q000627:therapeutic use; D018015:Receptors, Calcitonin Gene-Related Peptide / Q000502:physiology
C505165:1-(N(2)-(3,4-dibromo-N-((4-(3,4-dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl)carbonyl)tyrosyl)lysyl)-4-(4-pyridinyl)piperazine; D001381:Azepines; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D004151:Dipeptides; D007093:Imidazoles; D011799:Quinazolines; D018015:Receptors, Calcitonin Gene-Related Peptide; C525458:telcagepant; D015740:Calcitonin Gene-Related Peptide