Migraine is a highly disabling neurovascular disorder characterized by a severe headache (associated with nausea, photophobia and/or phonophobia), and trigeminovascular system activation involving the release of calcitonin-gene related peptide (CGRP). Novel anti-migraine drugs target CGRP signaling through either stimulation of 5-HT_1F receptors on trigeminovascular nerves (resulting in inhibition of CGRP release) or direct blockade of CGRP or its receptor. Lasmiditan is a highly selective 5-HT_1F receptor agonist and, unlike the triptans, is devoid of vasoconstrictive properties, allowing its use in patients with cardiovascular risk. Since lasmiditan can actively penetrate the blood-brain barrier, central therapeutic as well as side effects mediated by 5-HT_1F receptor activation should be further investigated. Other novel anti-migraine drugs target CGRP signaling directly. This neuropeptide can be targeted by the monoclonal antibodies eptinezumab, fremanezumab and galcanezumab, or by CGRP-neutralizing L-aptamers called Spiegelmers. The CGRP receptor can be targeted by the monoclonal antibody erenumab, or by small-molecule antagonists called gepants. Currently, rimegepant and ubrogepant have been developed for acute migraine treatment, while atogepant is studied for migraine prophylaxis. Of these drugs targeting CGRP signaling directly, eptinezumab, erenumab, fremanezumab, galcanezumab, rimegepant and ubrogepant have been approved for clinical use, while atogepant is in the last stage before approval. Although all of these drugs seem highly promising for migraine treatment, their safety should be investigated in the long-term. Moreover, the exact mechanism(s) of action of these drugs need to be elucidated further, to increase both safety and efficacy and to increase the number of responders to the different treatments, so that all migraine patients can satisfactorily be treated.

偏头痛是一种高度致残的神经血管疾病，其特征是严重的头痛（与恶心，畏光和/或声音恐惧症相关），以及涉及降钙素基因相关肽（CGRP）释放的三叉神经血管系统激活。新型抗偏头痛药物通过刺激三叉神经血管神经上的5-HT _1F受体（导致CGRP释放受到抑制）或直接阻断CGRP或其受体来靶向CGRP信号传导。Lasmiditan是一种高度选择性的5-HT _1F受体激动剂，与曲普坦类药物不同，它没有血管收缩特性，因此可用于有心血管风险的患者。由于Lamiditan可以主动穿透血脑屏障，因此由5-HT _1F介导的中枢治疗以及副作用受体激活应进一步研究。其他新型抗偏头痛药物直接靶向CGRP信号转导。该神经肽可被单克隆抗体eptinezumab，fremanezumab和galcanezumab靶向，或被CGRP中和的Spiegelmers的L-适体靶向。CGRP受体可以被单克隆抗体erenumab靶向，也可以被称为gepant的小分子拮抗剂靶向。目前，开发了瑞格非特和ubrogepant用于急性偏头痛的治疗，同时研究了Atogepant可以预防偏头痛。在直接靶向CGRP信号的这些药物中，已批准将eptinezumab，erenumab，fremanezumab，galcanezumab，rimegepant和ubrogepant用于临床，而atogepant则处于批准的最后阶段。尽管所有这些药物在偏头痛治疗中似乎都非常有前途，他们的安全性应进行长期调查。此外，还需要进一步阐明这些药物的确切作用机制，以增加安全性和疗效，并增加对不同治疗方法的反应者数量，以便所有偏头痛患者都能得到满意的治疗。