Reuter Uwe, Israel Heike, Neeb Lars
Hochschulambulanz und Klinik für Neurologie, Charité-Universitätsmedizin Berlin, Chariteplatz 1, 10117 Berlin, Germany.
Department of Neurology, Charite Universitätsmedizin Berlin, Berlin, Germany.
Ther Adv Neurol Disord. 2015 Jan;8(1):46-54. doi: 10.1177/1756285614562419.
More than 20 years have passed without the launch of a new substance class for acute migraine therapy. Triptans were the latest class of substances which successfully passed all developmental stages with a significant antimigraine efficacy and a sufficient safety profile. New drugs with a better adverse event profile and at least similar efficacy are needed for migraine subjects who cannot tolerate triptans for attack treatment. Lasmiditan is a novel highly specific 5-HT1F receptor agonist currently in clinical trials for acute migraine therapy and devoid of vasoconstriction in coronary arteries as determined in a surrogate assay. In both phase II randomized, placebo-controlled trials in acute migraine the primary endpoint was met. For the intravenous formulation a clear dose-dependent effect on headaches could be determined. Lasmiditan tablets in doses of 50-400 mg show significant headache relief after 2 hours compared with placebo and improved accompanying symptoms. This substance is chemically clearly different from other antimigraine drugs, which is also reflected by its dose-dependent adverse event profile chiefly including dizziness, vertigo, paresthesia and fatigue. Adverse events are usually linked to the central nervous system. Future phase III clinical trials with an active triptan comparator or in a preferential trial design will allow a better comparison of lasmiditan and triptans. They will also determine whether lasmiditan will become available to the migraine patient.
20多年过去了，急性偏头痛治疗领域一直没有推出新的药物类别。曲坦类药物是最近一类成功通过所有研发阶段的药物，具有显著的抗偏头痛疗效和足够的安全性。对于不能耐受曲坦类药物进行发作治疗的偏头痛患者，需要有不良事件谱更好且疗效至少相似的新药。拉米地坦是一种新型的高特异性5-HT1F受体激动剂，目前正处于急性偏头痛治疗的临床试验阶段，在一项替代试验中确定其在冠状动脉中无血管收缩作用。在两项急性偏头痛的II期随机、安慰剂对照试验中均达到了主要终点。对于静脉制剂，可以确定其对头痛有明显的剂量依赖性效应。与安慰剂相比，50-400毫克剂量的拉米地坦片在2小时后能显著缓解头痛，并改善伴随症状。这种药物在化学上与其他抗偏头痛药物明显不同，这也体现在其剂量依赖性不良事件谱上，主要包括头晕、眩晕、感觉异常和疲劳。不良事件通常与中枢神经系统有关。未来进行的有活性曲坦类药物对照的III期临床试验或采用优先试验设计，将能更好地比较拉米地坦和曲坦类药物。这些试验还将确定拉米地坦是否能为偏头痛患者所用。
