Migraine is a neurovascular disorder that involves activation of the trigeminovascular system and cranial vasodilation mediated by release of calcitonin gene-related peptide (CGRP).

The gold standard for acute migraine treatment are the triptans, 5-HT_1B/1D/(1F) receptor agonists. Their actions are thought to be mediated through activation of: (i) 5-HT_1B receptors in cranial blood vessels with subsequent cranial vasoconstriction; (ii) prejunctional 5-HT_1D receptors on trigeminal fibers that inhibit trigeminal CGRP release; and (iii) 5-HT_1B/1D/1F receptors in central nervous system involved in (anti)nociceptive modulation. Unfortunately, coronary arteries also express 5-HT_1B receptors whose activation would produce coronary vasoconstriction; hence, triptans are contraindicated in patients with cardiovascular disease. In addition, since migraineurs have an increased cardiovascular risk, it is important to develop antimigraine drugs devoid of vascular (side) effects.

Ditans, here defined as selective 5-HT_1F receptor agonists, were developed on the basis that most of the triptans activate trigeminal 5-HT_1F receptors, which may explain part of the triptans' antimigraine action. Amongst the ditans, lasmiditan: (i) fails to constrict human coronary arteries; and (ii) is effective for the acute treatment of migraine in preliminary Phase III clinical trials. Admittedly, the exact site of action is still unknown, but lasmiditan possess a high lipophilicity, which suggests a direct action on the central descending antinociceptive pathways. Furthermore, since 5-HT_1F receptors are located on trigeminal fibers, they could modulate CGRP release.

This review will be particularly focussed on the similarities and differences between the triptans and the ditans, their proposed sites of action, side effects and their cardiovascular risk profile.

偏头痛是一种神经血管疾病，涉及通过释放降钙素基因相关肽（CGRP）介导的三叉神经血管系统的激活和颅内血管舒张。

急性偏头痛治疗的金标准是曲普坦，5-HT _{1B / 1D /（1F）}受体激动剂。据认为，它们的作用是通过激活以下物质介导的：（i）颅内血管中的5-HT _1B受体伴有随后的颅内血管收缩；（ii）三叉神经纤维上的结前5-HT _1D受体抑制三叉神经CGRP释放；（iii）中枢神经系统中参与（抗）伤害感受调节的5-HT _{1B / 1D / 1F}受体。不幸的是，冠状动脉也表达5-HT _1B激活会产生冠状血管收缩的受体；因此，曲普坦是心血管疾病患者的禁忌症。此外，由于偏头痛患者的心血管风险增加，因此开发无血管副作用的抗偏头痛药物非常重要。

Ditans，在此定义为选择性5-HT _1F受体激动剂，是基于大多数曲普坦类化合物激活三叉神经5-HT _1F受体而开发的，这可能解释了曲普坦类药物的抗偏头痛作用。在地丹中，拉米坦是：（i）无法收缩人冠状动脉；（ii）在初步的III期临床试验中对偏头痛的急性治疗有效。诚然，确切的作用部位仍是未知的，但是Lasmiditan具有很高的亲脂性，这表明对中枢性降伤害感受途径有直接作用。此外，由于5-HT _1F受体位于三叉神经纤维上，因此它们可以调节CGRP的释放。

这篇综述将特别着重于曲普坦和地丹斯之间的异同，拟议的作用部位，副作用及其心血管风险状况。