Ramadan N M
Lilly Research Laboratories, Eli Lilly & Co. and Indiana University School of Medicine, Indianapolis, Indiana 46285, USA.
Curr Med Res Opin. 2001;17 Suppl 1:s71-80. doi: 10.1185/0300799039117001.
The introduction of sumatriptan, a selective 5-HT(1B/1D) agonist, for the treatment of migraine sparked a new era of drug research in this field. Many novel targets have since been developed, and tested in the clinic. The promise of these approaches is to deliver an anti-migraine compound with the optimal efficacy and safety profile. In this chapter, blind alleys in anti-migraine development are discussed. The failing soldiers have included the NK-1 antagonists, some second-generation 5-HT(1B/1D) agonists, CP-122,288, 4991W93, the neurosteroid ganaxolone, selective 5-HT(1F) (LY334370) and 5-HT(1D) agonists (PNU-142,633), and the endothelin-1 antagonist bosentan. Some of these promising targets failed to demonstrate clinical efficacy, while others were stopped for preclinical toxicity.
选择性5-羟色胺（5-HT）（1B/1D）受体激动剂舒马曲坦的引入开启了偏头痛治疗药物研究的新时代。此后，许多新靶点被开发出来并在临床上进行了测试。这些方法的前景是提供一种具有最佳疗效和安全性的抗偏头痛化合物。在本章中，将讨论抗偏头痛药物研发中的误区。失败的药物包括神经激肽-1（NK-1）拮抗剂、一些第二代5-HT（1B/1D）激动剂、CP-122,288、4991W93、神经甾体加奈索酮、选择性5-HT（1F）（LY334370）和5-HT（1D）激动剂（PNU-142,633）以及内皮素-1拮抗剂波生坦。其中一些有前景的靶点未能证明临床疗效，而其他一些则因临床前毒性而停止研发。
