title: The tortuous road to an ideal CGRP function blocker for the treatment of migraine.
abstract: The critical role of Calcitonin Gene-Related Peptide (CGRP) in migraine has been validated, with two small molecule CGRP antagonists BIBN4096BS and MK-0974 demonstrating efficacy in the reversal of acute migraine attack. Multiple approaches have been taken to find the ideal agent that most effectively inhibits CGRP's function. Here, we have summarized the progress made in recent years, including the identification and optimization of an orally bioavailable small molecule CGRP receptor antagonist. We also describe other interventions such as scavenging of CGRP itself. The advantages and disadvantages of these distinct approaches are discussed.
authors.affiliation: Department of Pharmacokinetics and Drug Metabolism, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320-1799, USA.
authors.forename: Carl D
authors.initials: CD
authors.lastname: Davis
authors.forename: Cen
authors.initials: C
authors.lastname: Xu
mesh_terms: D001381:Azepines / Q000494:pharmacology / Q000627:therapeutic use*; D015740:Calcitonin Gene-Related Peptide / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D007093:Imidazoles / Q000494:pharmacology / Q000627:therapeutic use*; D008881:Migraine Disorders / Q000188:drug therapy*; D010879:Piperazines / Q000494:pharmacology / Q000627:therapeutic use*; D011799:Quinazolines / Q000494:pharmacology / Q000627:therapeutic use*; D018015:Receptors, Calcitonin Gene-Related Peptide / Q000502:physiology; D013329:Structure-Activity Relationship; D014664:Vasodilation / Q000187:drug effects
chemical_list: D001381:Azepines; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D007093:Imidazoles; D010879:Piperazines; D011799:Quinazolines; D018015:Receptors, Calcitonin Gene-Related Peptide; C525458:telcagepant; D015740:Calcitonin Gene-Related Peptide; C406305:olcegepant