Calcitonin gene-related peptide receptor antagonists for the treatment of migraine: a patent review.
BACKGROUND
Migraine is a debilitating headache disorder which affects approximately 12% of the general population and is the cause of significant loss of productivity (i.e., lost time from work or school) for those afflicted. The current standard of care, the 5-HT(1B/1D) agonists known as triptans, is contraindicated in patients with cardiovascular disease due to their inherent vasoconstrictive activity; thus, there is a need to develop an alternative therapy for the treatment of the disorder.


OBJECTIVE
This article reviews patent publications related to the use of small molecule calcitonin gene-related peptide (CGRP) receptor antagonists for the treatment of migraine that have appeared in the literature within the past decade. The commentary is supplemented by information presented in journal articles and focuses on the activity of several major pharmaceutical companies in the field.


CONCLUSIONS
Two small molecule CGRP receptor antagonists, olcegepant and telcagepant, have been shown to be clinically efficacious in the treatment of migraine, and thus provide validation of this novel therapeutic mechanism.
Paone
Daniel V
DV
Department of Medicinal Chemistry, Merck Research Laboratories, West Point, PA 19486, USA. daniel_paone@merck.com
Staas
Donnette D
DD
D000818:Animals; D001381:Azepines / Q000494:pharmacology / Q000627:therapeutic use; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D004151:Dipeptides / Q000494:pharmacology / Q000627:therapeutic use; D015195:Drug Design; D004345:Drug Industry; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology / Q000627:therapeutic use; D008881:Migraine Disorders / Q000188:drug therapy* / Q000503:physiopathology; D010330:Patents as Topic; D010879:Piperazines; D011799:Quinazolines / Q000494:pharmacology / Q000627:therapeutic use; D018015:Receptors, Calcitonin Gene-Related Peptide / Q000378:metabolism
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; C406305:olcegepant