Oswald Jessica C, Schuster Nathaniel M
UCSD Center for Pain Medicine, La Jolla, CA, USA,
J Pain Res. 2018 Oct 8;11:2221-2227. doi: 10.2147/JPR.S152216. eCollection 2018.
Now that the vascular hypothesis of migraine is no longer the prevailing theory of migraine pathogenesis, there is interest in developing acute migraine treatments that act exclusively on non-vascular targets. There is a large percentage of non-responders to current acute migraine treatments and the vasoconstriction associated with triptans limit their use in patients with pre-existing cardiovascular risk factors. Preferential 5-HT agonists have shown promising results in in vitro and early proof-of-concept trials. Lasmiditan, a highly selective 5-HT agonist, has completed two Phase III randomized, double blind, placebo-controlled clinical trials, with a third - a long-term, open-label safety study - still underway. Research to date suggests lasmiditan lacks vasoconstrictive properties and may be a safe and effective treatment option in patients refractory to current acute migraine medications or who have cardiovascular risk factors.
既然偏头痛的血管假说已不再是偏头痛发病机制的主流理论，那么开发仅作用于非血管靶点的急性偏头痛治疗方法就引起了人们的兴趣。目前的急性偏头痛治疗方法有很大比例的无反应者，并且与曲坦类药物相关的血管收缩限制了它们在已有心血管危险因素患者中的使用。选择性5-羟色胺（5-HT）激动剂在体外试验和早期概念验证试验中已显示出有前景的结果。拉斯米地坦是一种高度选择性的5-HT激动剂，已完成两项III期随机、双盲、安慰剂对照临床试验，第三项试验——一项长期、开放标签的安全性研究——仍在进行中。迄今为止的研究表明，拉斯米地坦缺乏血管收缩特性，对于目前急性偏头痛药物难治或有心血管危险因素的患者，它可能是一种安全有效的治疗选择。
