Jacobson Laura H, Callander Gabrielle E, Hoyer Daniel
Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, VIC, Australia.
Expert Rev Clin Pharmacol. 2014 Nov;7(6):711-30. doi: 10.1586/17512433.2014.966813.
Suvorexant (Belsorma(®)) is the first orexin receptor antagonist approved by the US FDA (August 2014) for insomnia treatment. Following comprehensive Phase II/III studies, with up to 12 months of treatment in adult and elderly patients, there is little doubt that suvorexant induces and maintains sleep. However, the FDA and sponsor disagreed about effective versus safe doses (November 2012). The FDA considered that 5-15 mg were efficient and probably safe, whereas the sponsors had proposed 15-40 mg. The final approved doses are 5, 10, 15 and 20 mg. The major issues are next-morning somnolence and safety as seen in driving tests, with possible signs of muscle weakness, weird dreams, sleep walking, other nighttime behaviors and suicidal ideation. Despite its limitations, suvorexant's market entry offers a truly novel treatment for insomnia, paving the way for follow-up compounds and opening therapeutic avenues in other disorders for orexin receptor modulating compounds.
苏沃雷生（Belsorma(®)）是美国食品药品监督管理局（2014年8月）批准用于治疗失眠的首个食欲素受体拮抗剂。在全面的II/III期研究之后，对成年和老年患者进行了长达12个月的治疗，毫无疑问，苏沃雷生可诱导并维持睡眠。然而，美国食品药品监督管理局和申办方在有效剂量与安全剂量方面存在分歧（2012年11月）。美国食品药品监督管理局认为5 - 15毫克有效且可能安全，而申办方提议的剂量为15 - 40毫克。最终批准的剂量为5、10、15和20毫克。主要问题是驾驶测试中出现的次晨嗜睡和安全性，可能伴有肌肉无力、怪异梦境、梦游、其他夜间行为以及自杀意念的迹象。尽管存在局限性，但苏沃雷生的上市为失眠提供了一种全新的治疗方法，为后续化合物铺平了道路，并为食欲素受体调节化合物在其他疾病中的治疗开辟了途径。
