Significantly different effects of tetrahydroberberrubine enantiomers on dopamine D1/D2 receptors revealed by experimental study and integrated in silico simulation.

ABSTRACT: Tetrahydroberberrubine (TU), an active tetrahydroprotoberberines (THPBs), is gaining increasing popularity as a potential candidate for treatment of anxiety and depression. One of its two enantiomers, l-TU, has been reported to be an antagonist of both D1 and D2 receptors, but the functional activity of the other enantiomer, d-TU, is still unknown. In this study, experiments were combined with in silico molecular simulations to (1) confirm and discover the functional activities of l-TU and d-TU, and (2) systematically evaluate the molecular mechanisms beyond the experimental observations. l-TU proved to be an antagonist of both D1 and D2 receptors (IC₅₀ = 385 nM and 985 nM, respectively), while d-TU shows no affinity against either D1 or D2 receptor, based on the cAMP assay (D1

SUBMITTER: Ge H 

PROVIDER: S-EPMC6768063 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature