A novel psychoanalytical approach: An electrochemical ligand-binding assay to screen antipsychotics

Schizophrenia treatment may see a paradigm shift due to development of new atypical antipsychotic drugs (APDs), with better tolerability due to more selective dopamine (DA) receptor blockade. Monitoring of these APD candidates in biological fluids is of great importance to reduce the development cost, to clarify the mechanism of action and ultimately to support the demonstration of efficacy of these molecules. Electrochemical approaches have attracted great attention for monitoring DA and APD levels but none of the methods developed so far aimed to screen APD candidates. Herein, by this work, we propose for the first time an electrochemical ligand-binding approach for antipsychotic drug screening where competitive binding of a novel APD and DA to a dopamine D3 receptor (D3R) was investigated by looking at electrochemical signals of DA and drug before and after D3R interaction. D3R peptide was incubated with DA and/or drug first and then changes in electrochemical oxidation signals of free DA and the drug was measured by cyclic voltammetry (CV) and differential pulse voltammetry (DPV). Circular Dichroism pectroscopy was used to investigate the secondary structure of the peptide upon binding with either drug and/or DA.