Elinzanetant to treat moderate to severe vasomotor symptoms (hot flushes) caused by menopause

Elinzanetant is an antagonist of neurokinin (NK)-1 and NK-3 receptors.

Mechanism of action:

• hypothalamic kisspeptin/neurokinin B/dynorphin (KNDy) neurons express several receptor/ligand pairs, including neurokinin (NK)–1 and NK-3 receptors and their respective ligands, substance P (SP) and neurokinin B (NKB)
• during and after the menopausal transition, declining estrogen levels lead to hypertrophy and hyperactivity of KNDy neurons, which is accompanied by an overexpression of neurotransmitters, including NKB and SP
  • this hyperactivation has been shown to be concurrent with thermoregulatory disruption that results in VMS (vasomotor symptoms)
  • SP and NK-1 receptors may also have a role in peripheral vasodilatation and primary insomnia
  • elinzanetant is a non-hormonal selective antagonist of NK1 and NK3 receptors (2)

A review notes (2)

• in two clinical trials, elinzanetant modestly reduced VMS frequency and severity more than placebo at 12 weeks
• in indirect comparisons, HRT is the most effective treatment for reducing the frequency of VMS symptoms, while NK3 antagonists show modest efficacy

Reference:

1. Panay N et al. Elinzanetant for the Treatment of Vasomotor Symptoms Associated With Menopause: A Phase 3 Randomized Clinical Trial. JAMA Intern Med. 2025 Nov 1;185(11):1319-1327.
2. Elinzanetant for menopause.Drug and Therapeutics Bulletin Published Online First: 26 November 2025.