Elinzanetant

Elinzanetant is a non-hormonal, selective, dual neurokinin 1 (NK-1) and 3 (NK-3) receptor antagonist indicated for the treatment of moderate to severe vasomotor symptoms (VMS) associated with menopause. Peptide neurotransmitters and neuropeptides, such as neurokinin A, Substance P, and neurokinin B (NKB), and kisspeptin, are involved in the regulation the neuroendocrine and reproductive function. During menopause, declining estrogen levels lead to hyperactivation of kisspeptin/NKB/dynorphin (KNDy) neurons in the brain, disrupting thermoregulation and causing VMS. Overexpression of neurokinin B and Substance P - a key endogenous ligand for NK1 receptors - in the hypothalamus of postmenopausal women was also reported. Substance P and NK1 receptor signalling has also been implicated in sleep disturbances and peripheral vasodilation in menopause.

Elinzanetant blocks NK-1 and NK-3 receptor signalling on these KNDy neurons, modulating neuronal activity involved in thermoregulation. Elinzanetant exhibits high affinity for human NK-1 receptors (mean K value of 0.37 nM) and NK-3 receptors (mean K value of 3.0 nM).