Pauwels P J, John G W
Centre de Recherche Pierre Fabre, Castres, France.
Clin Neuropharmacol. 1999 May-Jun;22(3):123-36.
Serotonin (5-hydroxytryptamine; 5-HT) is thought to play an important role in the pathogenesis of migraine. The discovery of the 5-HT1B/1D/1F agonist sumatriptan constitutes a substantial advance in the acute treatment of migraine, though it displays a number of nonnegligible shortcomings. Today, a number of second-generation drugs derived from tryptamine are under advanced clinical development or are about to be marketed worldwide for the acute treatment of migraine. These tryptamine derivatives display partial agonist properties at 5-HT1B/1D receptors. It is not yet clearly established whether these agents represent a major improvement over sumatriptan in therapeutic effectiveness. Most of them also show affinity for 5-ht1F binding sites and have better oral pharmacokinetics than sumatriptan. The acute antimigraine effects of this second-generation of triptans seem to be obtained in largely the same way as with sumatriptan: by cranial vasoconstriction and inhibition of trigeminovascular activation from both peripheral and central projections. Future directions in migraine therapy should focus on agents that exhibit high intrinsic activity at 5-HT1B/1D receptors, offer a good safety profile, and demonstrate long-lasting action which might also be considered in migraine prophylaxis.
血清素（5-羟色胺；5-HT）被认为在偏头痛的发病机制中起重要作用。5-HT1B/1D/1F激动剂舒马曲坦的发现是偏头痛急性治疗方面的重大进展，不过它也存在一些不可忽视的缺点。如今，多种源自色胺的第二代药物正处于临床开发后期或即将在全球上市用于偏头痛的急性治疗。这些色胺衍生物在5-HT1B/1D受体上表现出部分激动剂特性。这些药物在治疗效果上是否比舒马曲坦有重大改进尚未明确确定。它们中的大多数还对5-ht1F结合位点有亲和力，并且口服药代动力学比舒马曲坦更好。第二代曲坦类药物的急性抗偏头痛作用似乎在很大程度上与舒马曲坦相同：通过颅血管收缩以及抑制来自外周和中枢投射的三叉神经血管激活。偏头痛治疗的未来方向应聚焦于在5-HT1B/1D受体上表现出高内在活性、具有良好安全性且作用持久的药物，这些药物也可考虑用于偏头痛预防。
