Headache Group, Department of Neurology, University of California, San Francisco, 1701 Divisadero St, San Francisco, CA, 94115, USA.
CNS Drugs. 2014 Jan;28(1):11-7. doi: 10.1007/s40263-013-0126-2.
Migraine is a common and highly disabling neurological disorder. Despite the complexity of its pathophysiology, substantial advances have been achieved over the past 20 years in its understanding, as well as the development of pharmacological treatment options. The development of serotonin 5-HT(1B/1D) receptor agonists ("triptans") substantially improved the acute treatment of migraine attacks. However, many migraineurs do not respond satisfactorily to triptans and cardiovascular co-morbidities limit their use in a significant number of patients. As migraine is increasingly considered to be a disorder of the brain, and preclinical and clinical data indicate that the observed vasodilation is merely an epiphenomenon, research has recently focused on the development of neurally acting compounds that lack vasoconstrictor properties. This review highlights the most important pharmacological targets for which compounds have been developed that are highly likely to enter or have already advanced into clinical trials for the acute and preventive treatment of migraine. In this context, preclinical and clinical data on compounds acting on calcitonin gene-related peptide or its receptor, the 5-HT(1F) receptor, nitric oxide synthase, and acid-sensing ion channel blockers are discussed.
偏头痛是一种常见且高度致残的神经系统疾病。尽管其病理生理学十分复杂，但在过去 20 年中，人们在理解偏头痛以及开发药物治疗选择方面取得了重大进展。5-羟色胺 5-HT(1B/1D)受体激动剂（“曲坦类药物”）的开发极大地改善了偏头痛发作的急性治疗。然而，许多偏头痛患者对曲坦类药物的反应并不满意，而且心血管合并症限制了它们在相当数量的患者中的使用。由于偏头痛越来越被认为是一种大脑疾病，并且临床前和临床数据表明观察到的血管扩张仅仅是一种伴随现象，因此最近的研究重点是开发缺乏血管收缩特性的神经作用化合物。这篇综述强调了最有前途的药理学靶点，这些靶点已经开发出了许多可能进入或已经进入偏头痛急性和预防性治疗临床试验的化合物。在这方面，讨论了作用于降钙素基因相关肽或其受体、5-HT(1F)受体、一氧化氮合酶和酸感应离子通道阻滞剂的化合物的临床前和临床数据。
