Annika Balzulat, W Felix Zhu, Cathrin Flauaus, Victor Hernandez-Olmos, Jan Heering, Sunesh Sethumadhavan, Mariam Dubiel, Annika Frank, Amelie Menge, Maureen Hebchen, Katharina Metzner, Ruirui Lu, Robert Lukowski, Peter Ruth, Stefan Knapp, Susanne Müller, Dieter Steinhilber, Inga Hänelt, Holger Stark, Ewgenij Proschak, Achim Schmidtko
Various disorders are accompanied by histamine-independent itching, which is often resistant to the currently available therapies. Here, it is reported that the pharmacological activation of Slack (Kcnt1, KNa 1.1), a potassium channel highly expressed in itch-sensitive sensory neurons, has therapeutic potential for the treatment of itching. Based on the Slack-activating antipsychotic drug, loxapine, a series of new derivatives with improved pharmacodynamic and pharmacokinetic profiles is designed that enables to validate Slack as a pharmacological target in vivo...
February 13, 2024: Advanced Science (Weinheim, Baden-Wurttemberg, Germany)