Rizzoli Paul B
Department of Neurology, Brigham and Women's Faulkner Hospital, John R. Graham Headache Center, Boston, MA, USA.
Neuropsychiatr Dis Treat. 2014 Mar 31;10:547-52. doi: 10.2147/NDT.S25531. eCollection 2014.
The serotonin receptor agonist triptan drugs (5-HT1B/1D receptor agonists) have been in use for over 20 years in the abortive management of migraine. Although clearly effective, their ability to produce vasoconstriction in cerebral and coronary arteries, thought to be mediated by their high affinity for the 5-HT1B receptor, has been a limitation to their use in certain patient populations. Variable potency triptan binding at the 5-HT1F receptor occurs in addition to binding at the 5-HT1B and 5-HT1D receptors. A more selective serotonin agonist without 5-HT1B-mediated vasoconstriction might prove efficacious yet safer. The 5-HT1F receptor has been targeted as a site of action for such a drug. In experimental models, 5-HT1F receptor agonists have been shown to block neurogenic inflammation and c-Fos expression in neural tissue and, as well, show no evidence of vasoconstriction in vascular tissue models in vitro. In clinical trials, efficacy in the abortive management of migraine has been established. Lasmiditan (LY573144), a selective 5-HT1F receptor agonist (K1=2.21 μM), showed efficacy in its primary endpoint, with a 2-hour placebo-subtracted headache response of 28.8%, though with frequent reports of dizziness, paresthesias, and vertigo. Study results support an emerging central neuronal mechanism of migraine pathophysiology. This review traces the history and use of 5-HT1F receptor agonists, now referred to as neurally acting anti-migraine agents in migraine management.
血清素受体激动剂曲坦类药物（5-HT1B/1D受体激动剂）已用于偏头痛的预防性治疗二十多年。尽管其疗效显著，但因其对5-HT1B受体具有高亲和力，从而导致其在脑动脉和冠状动脉中产生血管收缩的能力，这限制了其在某些患者群体中的使用。除了与5-HT1B和5-HT1D受体结合外，曲坦类药物还会与5-HT1F受体发生不同程度的结合。一种更具选择性且无5-HT1B介导血管收缩作用的血清素激动剂可能会被证明更有效且更安全。5-HT1F受体已成为这类药物的作用靶点。在实验模型中，5-HT1F受体激动剂已被证明可阻断神经源性炎症和神经组织中的c-Fos表达，并且在体外血管组织模型中未显示出血管收缩的迹象。在临床试验中，已证实其在偏头痛预防性治疗中的疗效。拉米地坦（LY573144）是一种选择性5-HT1F受体激动剂（K1 = 2.21 μM），在其主要终点显示出疗效，减去安慰剂后2小时的头痛缓解率为28.8%，不过常有头晕、感觉异常和眩晕的报告。研究结果支持偏头痛病理生理学中一种新出现的中枢神经元机制。本综述追溯了5-HT1F受体激动剂的历史和应用，现在其在偏头痛治疗中被称为神经作用性抗偏头痛药物。
