In vitro and in silico analysis of the effects of D₂ receptor antagonist target binding kinetics on the cellular response to fluctuating dopamine concentrations.

ABSTRACT:

Background and purpose

Target binding kinetics influence the time course of the drug effect (pharmacodynamics) both (i) directly, by affecting the time course of target occupancy, driven by the pharmacokinetics of the drug, competition with endogenous ligands and target turnover, and (ii) indirectly, by affecting signal transduction and homeostatic feedback. For dopamine D₂ receptor antagonists, it has been hypothesized that fast receptor binding kinetics cause fewer side effects, because part of the dynamics of the dopaminergic system is preserved by displacement of these antagonists.

Experimental approach

Target binding kinetics of D₂ receptor antagonists and signal transduction after dopamine and D₂ receptor antagonist exposure were measur

SUBMITTER: de Witte WEA 

PROVIDER: S-EPMC6177617 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature