1 Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
2 NIHR-Wellcome Trust King's Clinical Research Facility, King's College Hospital, London, UK.
Cephalalgia. 2019 Mar;39(3):420-427. doi: 10.1177/0333102418768095. Epub 2018 Apr 4.
A better understanding of the mechanisms underlying the migraine attack has reinforced the concept that migraine is a complex brain disease, and has paved the way for the development of new migraine specific acute treatments. In recent years, targeting the calcitonin gene-related peptide and its receptors has been one of the most promising pharmacological strategies for both acute and preventive treatment of migraine.
Randomized double-blind placebo-controlled trials have demonstrated the superiority of small molecule calcitonin gene-related peptide receptor antagonists (gepants) over placebo in treating acute migraine attacks measured as the two-hour pain free endpoint. Gepants also improved migraine associated symptoms, such as nausea, photophobia and phonophobia. Two of the class have had their development stopped because of hepatotoxicity, which is emerging as being due to metabolites. Gepants have a good tolerability and can be safely used in patients with stable cardiovascular disease.
Exciting results have been obtained targeting the calcitonin gene-related peptide pathway to abort acute migraine attacks, thus reinforcing the relevance of mechanism-based treatments specific for migraine.
对偏头痛发作机制的深入了解，强化了偏头痛是一种复杂脑部疾病的概念，并为新的偏头痛特异性急性治疗方法的发展铺平了道路。近年来，靶向降钙素基因相关肽及其受体已成为偏头痛急性和预防性治疗最有前途的药物治疗策略之一。
随机双盲安慰剂对照试验表明，与安慰剂相比，小分子降钙素基因相关肽受体拮抗剂（ gepants）在治疗急性偏头痛发作方面具有优势，以两小时无疼痛终点为衡量标准。 gepants 还改善了偏头痛相关症状，如恶心、畏光和畏声。由于肝毒性，该类药物中有两种已停止开发，而肝毒性可能是由于代谢物引起的。 gepants 具有良好的耐受性，可安全用于稳定型心血管疾病患者。
针对降钙素基因相关肽途径终止急性偏头痛发作的研究取得了令人兴奋的结果，从而进一步证实了针对偏头痛的基于机制的治疗方法的相关性。
