Potent hERG channel inhibition by sarizotan, an investigative treatment for Rett Syndrome.

ABSTRACT: Rett Syndrome (RTT) is an X-linked neurodevelopmental disorder associated with respiratory abnormalities and, in up to ~40% of patients, with prolongation of the cardiac QT_c interval. QT_c prolongation calls for cautious use of drugs with a propensity to inhibit hERG channels. The STARS trial has been undertaken to investigate the efficacy of sarizotan, a 5-HT_1A receptor agonist, at correcting RTT respiratory abnormalities. The present study investigated whether sarizotan inhibits hERG potassium channels and prolongs ventricular repolarization. Whole-cell patch-clamp measurements were made at 37 °C from hERG-expressing HEK293 cells. Docking analysis was conducted using a recent cryo-EM structure of hERG. Sarizotan was a potent inhibitor of hERG current (I

SUBMITTER: Cheng H 

PROVIDER: S-EPMC6856717 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature