Bell Ian M
Department of Discovery Chemistry, Merck Research Laboratories, West Point, Pennsylvania 19486, United States.
J Med Chem. 2014 Oct 9;57(19):7838-58. doi: 10.1021/jm500364u. Epub 2014 Jun 24.
Calcitonin gene-related peptide (CGRP) is a potent neuromodulator and vasodilator. It has been implicated in the pathogenesis of migraine by a number of lines of evidence, although its precise role has yet to be fully defined. Compelling evidence for the importance of CGRP in migraine has been provided by clinical trials with multiple small molecule CGRP receptor antagonists. These clinical studies have shown that blockade of the CGRP receptor can produce antimigraine efficacy comparable to that of the gold standard triptan class of drugs with an incidence of adverse events that appears to be relatively low. The present review describes the discovery and development of these new antimigraine agents and highlights the challenges of identifying orally acting drugs that target a family B G-protein-coupled receptor.
降钙素基因相关肽（CGRP）是一种强效神经调节剂和血管舒张剂。尽管其确切作用尚未完全明确，但已有多项证据表明它与偏头痛的发病机制有关。多种小分子CGRP受体拮抗剂的临床试验为CGRP在偏头痛中的重要性提供了令人信服的证据。这些临床研究表明，阻断CGRP受体可产生与金标准曲坦类药物相当的抗偏头痛疗效，且不良事件发生率似乎相对较低。本综述描述了这些新型抗偏头痛药物的发现和开发，并强调了识别靶向B族G蛋白偶联受体的口服药物所面临的挑战。
