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For the treatment of moderate to severe vasomotor symptoms (VMS) due to menopause¹

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Mechanism of Action

The first and only dual neurokinin (NK) targeted therapy, an NK1 and NK3 receptor antagonist, approved for the treatment of moderate to severe VMS due to menopause1

Watch the LYNKUET® Mechanism of Action (MOA)

Science of vms
Science of vms

Kisspeptin/neurokinin B/dynorphin (KNDy) neurons located in the hypothalamus are thought to play a key role in thermoregulation.2-5 These neurons have NK1 and NK3 receptors.1

During menopause, KNDy neurons can become hyperactive, which is associated with overexpression of Substance P (SP) and Neurokinin B (NKB).4,6

  • NKB is known to be involved in the initiation of hot flashes via NK3 receptors on thermoregulatory KNDy neuronal pathways7,8

  • Scientific data indicates that SP, via NK1 receptors, is thought to amplify KNDy neuronal activity9-12

Overexpression during menopause
KNDy neuron hyperactivity is associated with overexpression of SP and NKB during menopause.4,6

LYNKUET (elinzanetant) mechanism of action

How LYNKUET Works1

LYNKUET is an NK1 and NK3 receptor antagonist
Inhibition of SP and NKB through antagonism (blocking) of NK1 and NK3 receptor signaling on KNDy neurons can modulate neuronal activity in thermoregulation associated with hot flashes.

LYNKUET has higher affinity for human NK1 receptors and NK3 receptors than for human NK2 receptors.* 

*pKi values: NK1 receptors, 8.7-10.2; NK3 receptors, 8.0-8.8; NK2 receptors, approximately 6.0.
 

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    • 1
      LYNKUET (elinzanetant) [prescribing information]. Whippany, NJ: Bayer HealthCare Pharmaceuticals, Inc.; August 2026.
    • 2
      Deecher DC, Dorries K. Understanding the pathophysiology of vasomotor symptoms (hot flushes and night sweats) that occur in perimenopause, menopause, and postmenopause life stages. Arch Womens Ment Health. 2007;10(6):247-257. doi:10.1007/s00737-007-0209-5
    • 3
      Tan CL, Knight ZA. Regulation of body temperature by the nervous system. Neuron. 2018;98(1):31-48. doi:10.1016/j.neuron.2018.02.022
    • 4
      Rance NE, Dacks PA, Mittelman-Smith MA, Romanovsky AA, Krajewski-Hall SJ. Modulation of body temperature and LH secretion by hypothalamic KNDy (kisspeptin, neurokinin B and dynorphin) neurons: a novel hypothesis on the mechanism of hot flushes. Front Neuroendocrinol. 2013;34(3):211-227. doi:10.1016/j.yfrne.2013.07.003
    • 5
      Reame NK. More promising news (mostly) on manipulating neurokinin B activity as a nonhormonal treatment of hot flashes. Menopause. 2020;27(4):375-376. doi:10.1097/GME.0000000000001530
    • 6
      Hager M, Goldstein T, Fitz V, Ott J. Elinzanetant, a new combined neurokinin-1/-3 receptor antagonist for the treatment of postmenopausal vasomotor symptoms. Expert Opin Pharmacother. 2024;25(7):783-789. doi:10.1080/14656566.2024.2358131
    • 7
      Christ JP, Navarro VM, Reed SD. Nonhormonal therapies for menopausal vasomotor symptoms. JAMA. 2023;330(13):1278-1279. doi:10.1001/jama.2023.15965
    • 8
      Modi M, Dhillo WS. Neurokinin 3 receptor antagonism: a novel treatment for menopausal hot flushes. Neuroendocrinology. 2019;109(3):242-248. doi:10.1159/000495889
    • 9
      Torres E, Wall EG, Navarro VM. Neurokinin receptor antagonists for vasomotor symptoms: from KNDy neurons to clinical translation. Nat Rev Endocrinol. 2026;22(7):387-403. doi:10.1038/s41574-026-01247-8
    • 10
      deCroft S, Boehm U, Herbison AE. Neurokinin B activates arcuate kisspeptin neurons through multiple tachykinin receptors in the male mouse. Endocrinology. 2013;154:2750-2760. doi:10.1210/en.2013-1231
    • 11
      Hrabovszky E, Borsay BÁ, Rácz K, et al. Substance P immunoreactivity exhibits frequent colocalization with kisspeptin and neurokinin B in the human infundibular region. PLoS ONE. 2013;8(8):e72369. doi:10.1371/journal.pone.0072369
    • 12
      Kalil B, Ramaswamy S, Plant TM. The distribution of substance P and kisspeptin in the mediobasal hypothalamus of the male rhesus monkey and a comparison of intravenous administration of these peptides to release GnRH as reflected by LH secretion. Neuroendocrinol. 2016;103(6):711-723. doi:10.1159/000442420