The role of CGRP in the pathophysiology of migraine and efficacy of CGRP receptor antagonists as acute antimigraine drugs.
Migraine is a highly prevalent neurovascular disorder that can be provoked by infusion of calcitonin gene-related peptide (CGRP). CGRP, a neuropeptide released from activated trigeminal sensory nerves, dilates intracranial and extracranial blood vessels and centrally modulates vascular nociception. On this basis, it has been proposed that: (i) CGRP may play an important role in the pathophysiology of migraine; and (ii) blockade of CGRP receptors may abort migraine. With the advent of potent and selective CGRP receptor antagonists, the importance of CGRP in the pathophysiology of migraine and the therapeutic principle of CGRP receptor antagonism were clearly established. Indeed, both olcegepant (BIBN4096BS, given intravenously) and telcagepant (MK-0974, given orally) have been shown to be safe, well tolerated and effective acute antimigraine agents in phase I, phase II, and for telcagepant phase III, studies. However, recent data reported elevated liver transaminases when telcagepant was dosed twice daily for three months for the prevention of migraine rather than acutely. The potential for a specific acute antimigraine drug, without producing vasoconstriction or vascular side effects and with an efficacy comparable to triptans, is enormous. The present review will discuss the role of CGRP in the pathophysiology of migraine and the various treatment modalities that are currently available to target this neuropeptide.
Departamento de Farmacobiología, Cinvestav-Coapa, Czda. de los Tenorios 235, Col. Granjas-Coapa, Deleg. Tlalpan, C.P. 14330, México D.F., Mexico. cvillalon@cinvestav.mx
Carlos M
CM
Villalón
Jes
J
Olesen
D000700:Analgesics / Q000627:therapeutic use*; D000818:Animals; D001381:Azepines / Q000627:therapeutic use; D001921:Brain / Q000098:blood supply / Q000503:physiopathology; D015740:Calcitonin Gene-Related Peptide / Q000502:physiology; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D004151:Dipeptides / Q000737:chemistry / Q000627:therapeutic use; D016503:Drug Delivery Systems; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use; D008881:Migraine Disorders / Q000188:drug therapy* / Q000503:physiopathology*; D010879:Piperazines; D011799:Quinazolines / Q000737:chemistry / Q000627:therapeutic use; D018015:Receptors, Calcitonin Gene-Related Peptide / Q000819:agonists / Q000502:physiology
D000700:Analgesics; D001381:Azepines; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D004151:Dipeptides; D007093:Imidazoles; D010879:Piperazines; D011799:Quinazolines; D018015:Receptors, Calcitonin Gene-Related Peptide; C525458:telcagepant; D015740:Calcitonin Gene-Related Peptide; C406305:olcegepant