Neurokinin 3 receptor antagonists – prime time?

Abstract

Vasomotor symptoms (hot flushes, flashes, night sweats) occur in the majority of menopausal women, and are reported as being of the highest symptom priority as they often persist over many years and can be highly disruptive. Hormone therapy is the most effective available treatment but is not without risk if taken long term, and is sometimes contraindicated; for example, in women with a personal or family history of breast cancer, which is the most common female cancer worldwide. Other treatment alternatives are not as efficacious, can cause side effects, and/or are not widely available. A new, effective, targeted treatment could therefore benefit millions of women worldwide. This became possible to investigate after accumulated evidence from both animal and human models implicated heightened signaling of a hypothalamic neuropeptide together with its receptor (neurokinin B/NK3R) in the etiology of sex-steroid-deficient vasomotor symptoms. Four clinical trials of three chemically distinct oral NK3R antagonists for the treatment of menopausal flushes have since completed and published, which consistently demonstrate efficacy and tolerability of these agents. These suggest great promise to change practice in the future if ongoing further larger-scale studies of longer duration confirm the same; as, estrogen exposure will no longer be required to effectively and safely treat vasomotor symptoms.

摘要

大多数更年期女性都会出现血管舒缩症状（潮热、盗汗）, 据报道, 它是更年期女性的首要症状, 这是因为这些症状通常持续多年, 且危害严重。激素疗法是目前最有效的治疗方法, 但如果长期服用, 也并非没有风险, 有时甚至存在禁忌；例如, 乳腺癌是世界范围内女性最常见的恶性肿瘤, 激素治疗禁用于有乳腺癌病史或家族史的女性。其他治疗方法效果有限, 可能会引起副作用, 或是未广泛应用。因此, 一种新的、有效的、有针对性的治疗方法将使全世界数百万女性受益。从动物模型和人类模型中积累的证据表明, 下丘脑神经肽及其受体（神经激肽B/NK3R）的信号增强在性激素缺乏性血管舒缩症状的病因中起作用。这为开发新的治疗方法带来可能。已有四项关于三种化学性质完全不同的口服NK3R拮抗剂治疗更年期潮热的临床试验完成并发表, 试验结果一致证明了这些药物的有效性和耐受性。这强烈暗示着, 如果有持续时间更长且规模更大的研究也证实这一结论, 未来临床实践将产生变革；这是因为, 针对血管舒缩症状有效且安全的治疗手段将不再需要雌激素参与。

Keywords:

• Neurokinin 3 receptor antagonists
• vasomotor symptoms
• menopause
• hot flushes
• novel therapeutics

Potential conflict of interest

No potential conflict of interest was reported by the author.

Source of funding

Nil.