Glossary · Mechanisms

NK3 receptor antagonist

Also called: NK3 antagonist, Neurokinin-3 receptor antagonist.

Definition: NK3 receptor antagonists block the neurokinin-3 receptor in hypothalamic thermoregulatory neurons. By interrupting the excessive neurokinin B signaling that drives vasomotor symptoms after estrogen withdrawal, NK3 antagonists like fezolinetant reduce hot flashes without altering estrogen levels.

Detailed definition

NK3 receptor antagonists are a new class of non-hormonal vasomotor symptom medications targeting the KNDy neuron pathway. Estrogen normally restrains KNDy neuron activity; estrogen withdrawal at menopause leads to KNDy hypertrophy and excess neurokinin B (NKB) release, dysregulating thermoregulation through NK3 receptor signaling on downstream neurons. NK3 receptor antagonists block this pathway. Fezolinetant (Veozah) is the first FDA-approved NK3 antagonist (May 2023). Elinzanetant is an investigational dual NK1/NK3 antagonist with potentially additional sleep benefits and is in late-phase trials. The class represents the first mechanism-targeted non-hormonal vasomotor symptom approach, distinct from older options (SSRIs, gabapentin) that work downstream.

Why it matters in menopause

For women who cannot or do not want to use estrogen, NK3 receptor antagonists are the first non-hormonal option to target the underlying menopausal physiology. Fezolinetant is now standard-of-care option for severe vasomotor symptoms in breast cancer survivors and women with VTE history. The class will likely expand as elinzanetant and others advance.

Sources

External references: Wikipedia.

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