The thermoregulatory center in the brain hypothalamus is innervated by kisspeptin/neurokinin B/dynorphin (KNDy) neurons. These neurons are stimulated by the neuropeptide neurokinin B, acting at the neurokinin 3 receptors, and inhibited by estrogen.
The thermoregulatory center triggers heat dissipation effectors. Vasodilation in the skin causes heat loss, which is experienced as hot flashes, sweating, and chills.
Fezolinetant, in development for potential treatment of moderate to severe VMS associated with menopause, is a nonhormonal selective neurokinin-3 receptor (NK3R) antagonist that blocks NKB binding on the KNDy neuron, restoring normal sensitivity of the thermoregulatory center.
In this episode, Mr Wattar and Dr Talaulikar discuss the results of the Skylight 2 randomised trial published in The Journal of Clinical Endocrinology & Metabolism.
Watch the episode on YouTube: https://www.youtube.com/watch?v=lipj7NeHBNI
Full reference to the article: Johnson KA, Martin N, Nappi RE, Neal-Perry G, Shapiro M, Stute P, Thurston RC, Wolfman W, English M, Franklin C, Lee M. The Journal of Clinical Endocrinology & Metabolism (2023). Doi.org/10.1210/clinem/dgad058
