Clinical Division of Gynecological Endocrinology and Reproductive Medicine, Department of Obstetrics and Gynecology, Medical University of Vienna, Vienna, Austria.
Division of Reproductive Endocrinology and Infertility, Department of OB/GYN, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Expert Opin Pharmacother. 2024 May;25(7):783-789. doi: 10.1080/14656566.2024.2358131. Epub 2024 Jun 13.
In many postmenopausal women, quality of life is decreased due to vasomotor symptoms. Efficient and well-tolerated non-hormonal treatment options are needed.
The present review summarizes what is known about the etiology of postmenopausal vasomotor symptoms as a rationale for the mechanism of action of Elinzanetant, a new neurokinin (NK)-1/-3 receptor antagonist, as well as its efficacy and side effect profile.
Elinzanetant likely exerts an antagonistic effect on the NK-3 receptor in the preoptic thermoregulatory zone, but also an additional antagonistic effect on the NK-1 receptor possibly leading to a reduction in vasodilatation and heat-sensing neuro-activity. Elinzanetant's reported peak drug concentrations are reached within one hour and the terminal elimination half-life is approximately 15 hours. Two phase IIb clinical trials evaluated the safety profile and efficacy of several doses. There were no serious adverse events, which also included a lack of evidence of drug-related hepatotoxicity. Overall, Elinzanetant seems to be well-tolerated. In the SWITCH-1 study, the 120 mg/day and 160 mg/day regimen showed good efficacy for the treatment of vasomotor symptoms and led to significant improvements in quality of life. Thus, 120 mg oral Elinzanetant/day was used in phase III trials, whose results have not yet been published.
在许多绝经后妇女中，由于血管舒缩症状，生活质量下降。需要有效的、耐受良好的非激素治疗选择。
本综述总结了绝经后血管舒缩症状的病因学知识，作为新型神经激肽（NK）-1/-3 受体拮抗剂 Elinzanetant 的作用机制的理论基础，以及其疗效和副作用概况。
Elinzanetant 可能对视前区体温调节区的 NK-3 受体产生拮抗作用，但也可能对 NK-1 受体产生额外的拮抗作用，从而导致血管扩张和热感觉神经活动减少。Elinzanetant 的报告药物峰浓度在一小时内达到，终末消除半衰期约为 15 小时。两项 IIb 期临床试验评估了几种剂量的安全性概况和疗效。没有严重不良事件，也没有证据表明与药物相关的肝毒性。总体而言，Elinzanetant 耐受性良好。在 SWITCH-1 研究中，120mg/天和 160mg/天的方案对血管舒缩症状的治疗效果良好，并显著改善了生活质量。因此，在 III 期临床试验中使用了 120mg 口服 Elinzanetant/天，但其结果尚未公布。
